IBD Literature Report
Coverage: June 13, 2026 - June 20, 2026
145
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Biomarkers & Precision Medicine (21 papers)
Association between colonoscopic findings and fecal calprotectin levels in familial Mediterranean fever patients with gastrointestinal symptoms: a retrospective cohort study. Clinical rheumatology | 2026-06-18
Familial Mediterranean fever (FMF) is an autoinflammatory disease characterized by recurrent fever and serositis. Gastrointestinal involvement and subclinical intestinal inflammation have been reported in FMF, with elevated fecal calprotectin (FC) levels even during attack-free periods. This study aimed to investigate the relationship between colonoscopic findings and FC levels in pediatric FMF patients presenting with gastrointestinal symptoms. This retrospective cohort study included children under 18 years of age with FMF who underwent colonoscopy for gastrointestinal symptoms between 2018 and 2024. Patients were categorized into three groups based on colonoscopic findings: normal colonoscopy, nonspecific findings, and inflammatory bowel disease (IBD). Demographic data, laboratory results, and FC levels were analyzed. ROC analysis was performed to identify the FC cutoff value predictive of colitis. A total of 81 patients (median age 12 years; 51.9% male) were included. FC levels were significantly higher in the IBD group compared to other groups (p < 0.001). Albumin levels were lower in IBD patients (p = 0.013). ROC analysis revealed that an FC level below 123 µg/g predicted normal colonoscopic findings with 89.8% sensitivity and 84.4% specificity (AUC 0.902). FC may serve as a useful non-invasive biomarker for predicting colonoscopic abnormalities in pediatric FMF patients. An FC level below 123 µg/g appears to reliably predict normal colonoscopic findings, suggesting that unnecessary invasive procedures may be avoided in this subgroup. Key Points • Fecal calprotectin levels correlated with the severity of colonoscopic abnormalities in FMF patients with gastrointestinal symptoms. • A fecal calprotectin level below 123 µg/g feces strongly predicted normal colonoscopic findings. • Fecal calprotectin may serve as a useful non-invasive tool to reduce unnecessary colonoscopic procedures in pediatric FMF patients.
Dinçer BT, Urgancı N, Çavuşoğlu M, Özçelik G, Usta M
TIM3 signaling in effector T cells acts as an immunometabolic switch in the purine degradation pathway to suppress intestinal inflammation.★ Gastroenterology | 2026-06-17
Effector T lymphocytes have been shown to play a key role in inflammatory bowel diseases (IBD). However, the molecular pathways controlling their metabolism and functional activity remain poorly defined. We aimed to elucidate the role of the immune checkpoint receptor TIM3 for T cell signalling in IBD. We combined experimental colitis models in TIM3-deficient mice with analyses of human IBD and control samples. Blood and mucosal T cells were assessed using multi-colour flow cytometry, cytokine profiling, and untargeted metabolomics. Single-cell sequencing data were analysed. The TIM3 ligand galectin-9 was used to study TIM3 function. TIM3 expression was higher on blood Th1 cells and mucosal Th17 cells in IBD patients compared to controls, with levels being particularly high in anti-TNF refractory patients. Mice lacking TIM3 showed exacerbated oxazolone colitis and increased effector T cell activation. Metabolome profiling and functional analyses revealed that TIM3 signaling functions as an immunometabolic regulator, suppressing adenosine deaminase and the purine degradation pathway to keep effector T cells in an exhausted PD1+ state. However, insufficient availability of the TIM3 ligand galectin-9 limited effective TIM3 signalling in chronic inflammation. Treatment with galectin-9 ameliorated experimental colitis via adenosine deaminase inhibition. Moreover, in IBD T cells, galectin-9 induced an immunometabolic switch associated with reduction of terminally exhausted Th17 cells. TIM3 plays a key role in the immunometabolism of effector T cells in colitis by suppressing adenosine deaminase and the purine degradation pathway. Targeting the immunometabolic functions of effector T cells via TIM3 activation emerges as a promising strategy for chronic intestinal inflammation.
Knauss A, Gabel M, Kaufmann C, Loges L, Rath T, Atreya R, Radtke D, Grapp H, Gerlach K, Thoma OM
Zinc supplementation ameliorates colitis in mice by sensitizing pathogenic CD4+ T cells to ferroptosis. Clinical and experimental medicine | 2026-06-17
Inflammatory Bowel Disease (IBD) is driven by the hyperactivation of pathogenic Th1 and Th17 subsets. Although clinical zinc deficiency strongly correlates with severe IBD outcomes, the precise immunomodulatory mechanisms underlying this association remain unknown. To systematically investigate the role of zinc in CD4+ T cell fate determination and intestinal homeostasis, we evaluated its immunomodulatory dynamics using a murine colitis model alongside in vitro differentiation assays employing human primary naive CD4+ T cells. We found that zinc supplementation remarkably ameliorated experimental mucosal damage by abruptly halting the local infiltration of pathogenic CD4+ T cells. Both in vivo and in vitro analyses revealed that zinc does not merely stall T cell polarization, but actively sensitizes these effector subsets to cell demise. Comprehensive transcriptomic sequencing pinpointed the ferroptosis cascade as the critical mediator of this clearance mechanism. Specifically, zinc systematically suppressed T cell anti-ferroptotic defenses by downregulating GPX4 and SLC7A11, while concurrently amplifying pro-ferroptotic drivers such as ACSL4. This targeted metabolic stress profoundly sensitized hyperactive T cells to ferroptosis, effectively purging the inflammatory mucosal niche. Ultimately, these findings reframe the fundamental role of zinc in intestinal immune homeostasis, exposing ferroptosis as a druggable vulnerability in IBD and providing a strong mechanistic rationale for zinc-based clinical interventions.
Li Z, Cai J
Identification of potential biomarkers for ulcerative colitis based on multidimensional data analysis and investigation of the mechanisms of therapeutic effects. BMC gastroenterology | 2026-06-17
Based on multidimensional data analysis, potential biomarkers for ulcerative colitis were screened, and the effects of curcumin chitosan microspheres on the expression of key targets in ulcerative colitis and their role in alleviating inflammation were observed. Potential biomarkers related to UC progression were identified through differential expression analysis (using the limma package, with |log2FC| > 1 and corrected P < 0.05), weighted gene coexpression network analysis, and three machine learning algorithms (LASSO, random forest, SVM-RFE) on the basis of the datasets GSE107499 and GSE87473 in the GEO database. The core genes selected through this process were externally validated via the independent dataset GSE47908. A UC mouse model was constructed using 6-8-week-old C57BL/6 mice, and CCM was applied to the UC mice. Colonic tissues were collected for pathological examination and determination of inflammatory factor levels. Changes in the protein expression of the core genes were detected via immunohistochemistry. After rigorous screening and external validation, four core genes were finally identified: FCN3, FGR, HSD11B1 and PIM2. CCM treatment improved pathological damage and inflammatory factor levels in the colon tissue of UC mice, and the protein expression levels of FCN3, FGR, HSD11B1 and PIM2 in the colon tissue were inhibited. Four potential targets of UC, namely, FCN3, FGR, HSD11B1, and PIM2, were identified. CCM may improve the degree of the UC inflammatory response by downregulating the expression of key genes.
Yu S, Zhu Q, Yu C, Liu J, Han RPS, Xiang Y
Fibroblast growth factors (FGF) in the pathogenesis and treatment of inflammatory bowel diseases (IBD): An overview.Review The international journal of biochemistry & cell biology | 2026-06-16
Fibroblast growth factor (FGF) constitutes a diverse family of signaling proteins involved in cell proliferation, differentiation, angiogenesis, lymphangiogenesis and tissue regeneration. Emerging evidence suggests that FGFs may also play a pivotal role in inflammatory bowel diseases (IBD). IBD, comprising Crohn’s disease (CD) and ulcerative colitis (UC), is characterized by chronic, relapsing inflammation of the intestines, manifested primarily by persistent abdominal pain and severe diarrhea. In IBD, by activating specific fibroblast growth factor receptors (FGFRs), FGFs modulate the immune response, promote mucosal healing, and regulate extracellular matrix (ECM) remodeling, thereby maintaining intestinal barrier integrity. Expression levels of several FGFs, including FGF1, FGF2, FGF7, and FGF10 are upregulated in IBD. These alterations often reflect disease exacerbation and correlate with inflammatory markers, suggesting the potential of FGFs as biomarkers. Furthermore, studies in animal models of various gastrointestinal (GI) tract diseases demonstrate promising possibilities for the use of recombinant FGFs as a novel therapeutic approach to managing gut inflammation.
Jarzabek J, Jaczynska M, Kasprzak Z, Zakrzewska M, Salaga M
Comparative efficiency of leucine-rich alpha-2 glycoprotein and fecal calprotectin to assess endoscopic activity in Crohn’s disease: a prospective observational study.★ Inflammatory bowel diseases | 2026-06-16
Endoscopic healing is a key therapeutic target for Crohn’s disease (CD). However, endoscopy is invasive, and simple, non-invasive biomarkers are needed to assess endoscopic healing. Although leucine-rich alpha-2 glycoprotein (LRG) and fecal calprotectin (FC) are indicators of inflammatory bowel disease activity, few studies have directly compared them for endoscopic disease activity in CD. We aimed to compare the ability of these markers to assess endoscopic remission in CD. From October 2022 to December 2023, 100 patients with CD at Nagoya University Hospital were prospectively and consecutively enrolled. Endoscopic activity was assessed using the applied simple endoscopic score for Crohn’s disease (aSES-CD), incorporating small bowel lesions. The primary endpoint was the sensitivity of LRG and FC in endoscopic remission (aSES-CD ≤ 3), which was tested using McNemar’s exact test. Logistic regression analysis was used to identify factors associated with endoscopic remission. Overall, 84 patients were analyzed (79.8% male; median age 49.5 years). The receiver operating characteristic curve analysis yielded sensitivity/specificity values of 85.9%/90.0% for LRG and 70.3%/85.0% for FC, using cutoff values of 11 µg/mL (LRG) and 100 µg/g (FC) for endoscopic remission. Based on these values, a comparison of sensitivities between LRG and FC showed that LRG had significantly higher sensitivity (P = .013). In multivariate analysis, only LRG was an independent factor for endoscopic remission (odds ratio 3.016; 95% CI, 1.506-6.037). Compared with FC, LRG shows a higher sensitivity for assessing endoscopic remission. LRG may serve as a useful biomarker for endoscopic activity in CD. In this prospective study, serum LRG showed higher sensitivity and closer correlation with endoscopic activity than FC in Crohn’s disease, particularly for small-intestinal lesions, and may serve as a useful and practical biomarker.
Kawamura T, Yamamura T, Nakamura M, Maeda K, Sawada T, Ishikawa E, Murate K, Hirose T, Ishikawa T, Furukawa K
Molecular determinants of thromboinflammatory activation in inflammatory bowel disease.Review Journal of molecular medicine (Berlin, Germany) | 2026-06-16
Inflammatory bowel disease (IBD) is consistently associated with an increased risk of venous thromboembolism, particularly during active disease and hospitalization, yet thrombosis in this context extends beyond a transient inflammatory complication. Emerging evidence supports a unifying thromboinflammatory framework in which chronic intestinal inflammation promotes systemic vascular activation. Endothelial dysfunction represents a central interface in this process and is characterized by reduced nitric oxide bioavailability, increased expression of adhesion molecules, angiogenic remodeling, and glycocalyx disruption, collectively shifting the vascular surface toward a proadhesive and procoagulant phenotype. In parallel, dysregulation of coagulation pathways sustains thrombin generation through enhanced tissue factor signaling, elevated procoagulant factors, most consistently factor VIII, impaired endogenous anticoagulant mechanisms including the protein C and antithrombin systems, and features of hypofibrinolysis. Platelet activation further amplifies these disturbances via CD40 ligand (CD40L)-mediated endothelial crosstalk, platelet leukocyte aggregate formation, and imbalance of the von Willebrand factor (VWF)-ADAMTS13 axis, reinforcing a self perpetuating loop between inflammation and coagulation. Although mechanistic plausibility is strong and multiple biomarkers of endothelial and hemostatic activation have been described, much of the current evidence derives from cross sectional or associative studies, with limited prospective validation linking individual pathways to incident thrombotic outcomes in IBD specific cohorts. Taken together, thrombosis in IBD reflects sustained systemic thromboinflammatory dysregulation rather than an isolated complication of flares. Future longitudinal studies integrating vascular biomarkers with adjudicated thrombotic events are essential to refine risk stratification and inform individualized thromboprophylaxis strategies.
Šantić R, Pavlović N, Kumrić M, Vilović M, Božić J
Development and functional adaptation of intestinal macrophages across the lifespan.Review Clinical & translational immunology | 2026-06-16
Macrophages of the gastrointestinal system are central regulators of gut development, homeostasis and disease, yet their origin, functional diversification and life stage-specific roles remain incompletely integrated. This review aimed to provide a comprehensive synthesis of current knowledge on intestinal macrophage ontogeny, heterogeneity and function from prenatal development through adulthood and into the aging phase. We highlight emerging evidence defining embryonic and monocyte-derived macrophage populations, their specialised roles in tissue remodelling, immune regulation, vascular and neural support, and their dynamic turnover across the lifespan. The review also examines how disruption of key regulatory pathways, including those relating to interleukin 10 (IL10), transforming growth factor (TGFβ) and metabolic signalling, contributes to macrophage dysfunction in inflammatory bowel disease, as an example of a gastrointestinal disorder with macrophage involvement. By integrating findings from lineage-tracing, single-cell transcriptomics and functional studies, this review provides a unified framework for understanding intestinal macrophage biology across life stages. This review provides a strengthened understanding of intestinal macrophage biology and establishes a knowledge base for translational therapies that can modify macrophage function to target inflammatory disorders and maintain gut health.
Mustafa B, Hill-Yardin EL, Spencer SJ
Enteric neuroimmune interactions in health and disease.Review Trends in neurosciences | 2026-06-15
The intestine contains a dense intrinsic nervous system that is closely integrated with local immune cells to coordinate motility, barrier defense, and tissue repair. Recent studies, primarily in mice and supported by emerging human evidence, have identified diverse enteric neuroimmune pathways through which enteric neurons shape immune cell responses, while immune cells, in turn, influence neuronal survival and function across distinct intestinal compartments. These bidirectional interactions are increasingly implicated in intestinal disorders, including Hirschsprung’s disease, irritable bowel syndrome, inflammatory bowel disease, and infection-induced dysmotility. In this review, we summarize the anatomical basis and principal mechanisms of enteric neuroimmune communication, highlight recent advances in the field, and discuss key unresolved questions and future directions.
Qu Y, Zhang Y, Zhou S, Yang T, Chu C
Patient-matched transcriptomics of in vivo and in vitro colonic epithelium substantiate organoids as a translational model for ulcerative colitis. Scientific reports | 2026-06-14
Ulcerative colitis (UC) is characterized by cytokine-driven inflammation and barrier disruption in the colon, making epithelial dysfunction central to disease pathology. Intestinal epithelial organoids (IEOs) preserve donor-specific genetics and architecture, offering a promising model, but their ability to replicate patient-specific epithelial inflammation remains undetermined. To directly compare in vivo epithelial transcriptional states with defined cytokine-induced responses in vitro, we analyzed patient-matched transcriptomics from laser microdissected inflamed and uninflamed colonic epithelium and IEOs derived from uninflamed biopsies of the same UC patients. IEOs were stimulated with UC-relevant cytokines (TNF, IFNγ, IFNλ1, or TNF + IFNγ) or a cytokine cocktail (TNF, IL17, IL1β, IL22, Poly(I:C), IFNγ). Key inflammatory genes were validated by immunoblotting and immunostaining. Cytokine-stimulated IEOs recapitulated key in vivo epithelial inflammation, including interferon signaling, antigen presentation, and unfolded protein response pathways. Among the tested conditions, TNF + IFNγ combination and the cytokine cocktail most closely replicated UC epithelial inflammation, with concordance for over 350 UC-relevant genes and protein-level validation of IRF1, ERAP2, NOS2, DUOX2 confirmed patient-dependent expression between inflamed epithelium and cytokine-stimulated IEOs. Our study shows that cytokine-stimulated IEOs provide a robust, personalized platform for modeling epithelial inflammation, enabling discovery of epithelial-specific disease mechanisms and therapeutic targets.
Walaas GAE, Sridhar A, Kuraas LF, Sæterstad S, Schioldborg AY, Van Beelen Granlund A, Sandvik AK, Østvik AE, Bakke I, Bruland T
The dual balance of the cytokine network: key messengers of immune activation and triggers of cytokine storm.Review Biomarker research | 2026-06-12
The cytokine network is the central regulatory system for intercellular communication within the immune system. Its proper function depends on the dynamic balance between pro-inflammatory and anti-inflammatory cytokines. Through complex positive and negative feedback loops, this balance precisely regulates the intensity and duration of immune responses, thereby playing a critical role in both physiological and pathological states. This review systematically summarizes the compositional features and classification framework of the cytokine network, as well as the mechanisms by which it maintains homeostasis under physiological conditions. It further examines the manifestations of cytokine network imbalance in diseases such as sepsis, psoriasis, rheumatoid arthritis, inflammatory bowel disease, and cancer. Available evidence suggests that these imbalances drive disease onset and progression primarily through cascade amplification of pro-inflammatory signaling, insufficient generation of anti-inflammatory signals, and aberrant epigenetic modification. These pathological changes are strongly influenced by factors such as infection, autoimmune dysregulation, and the tumor microenvironment (TME), together constituting the core pathological axis of “cytokine imbalance-immune dysregulation-disease progression.” This review also summarizes current clinical strategies targeting the cytokine network, including monoclonal antibodies, Janus kinase (JAK) inhibitors, and emerging modalities such as bispecific antibodies and chimeric antigen receptor (CAR) cell therapy. In addition, it evaluates the clinical efficacy, potential risks, and future directions of these approaches. In summary, a deeper understanding of the binary balance within the cytokine network not only broadens our knowledge of immune regulation but also provides a theoretical basis and translational framework for the development of precision immune-targeted therapies.
Zhang Y, Guo D, Zhou Y, Wang C, Su G, Huang J, Wan Y, Zhang H, Wan H, Bo L
Coordinated IFN-γ/TNF Axis Drives Selective Loss of Activated Enteric Glia in Inflammatory Bowel Diseases.★ Cellular and molecular gastroenterology and hepatology | 2026-06-12
Enteric glial cells (EGCs) regulate gastrointestinal homeostasis and inflammation. While activated EGCs have been shown to support epithelial and immune balance in preclinical models, their functional status and turnover in inflammatory bowel diseases (IBD) remain poorly defined. This study aimed to identify EGC activation markers and assess their susceptibility to cytokine-driven death in IBD. We analysed 390 intestinal samples from IBD patients using bulk and single-nucleus RNA sequencing and validated findings across public datasets comprising over 1,160 patients and 19,000 EGC transcriptomes. We used multiple mouse models of gut inflammation, reporter-based glial sorting, transcriptomics, and glia-specific Casp8 deletion to dissect mechanisms of EGC activation and death. Ex vivo stimulation of sorted EGCs was used to assess cytokine-specific effects. We identified novel IBD subtype- and location-specific EGC activation markers, including osteopontin (SPP1), enriched in ulcerative colitis. Single-nucleus and single-cell data revealed that activated EGC clusters selectively upregulate cell death signatures with IBD EGC displaying necroptosis via phosphorylation of MLKL. In mice, acute Th1/Th17-driven inflammation rapidly induced EGC activation and necroptosis, impairing intestinal motility. Ex vivo, IFN-γ and TNF co-stimulation, but not individual cytokines, induced MLKL-dependent necroptosis in EGCs. Casp8-deficient EGCs were hypersensitive to TNF-induced death, confirming a Caspase-8 -dependent survival checkpoint. A proportion of activated EGC are selectively eliminated in IBD via cytokine-mediated necroptosis, driven by a coordinated IFN-γ/TNF axis. This process compromises enteric glial support functions and may contribute to IBD-associated dysmotility. Targeting glial survival may represent a novel therapeutic avenue.
Bubeck M, Penkert KA, Limberger H, Acera MG, Plattner C, Ziegler S, Muppirala A, Forster P, Jakob M, Gamez-Belmonte R
Genomic Research for Abdominal Pain in Patients with Irritable Bowel Syndrome or Inflammatory Bowel Disease Before and After Mind-Body Intervention. Journal of pain research | 2026-06-10
Abdominal pain is a hallmark symptom of both inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) and substantially impairs patients’ quality of life. Relaxation response-based mind-body intervention (RR-MBI) has been reported to improve disease-specific outcomes and pain catastrophizing in both disorders, accompanied by whole-blood transcriptomic changes. However, the transcriptional features potentially relevant to abdominal pain before and after RR-MBI in IBS and IBD remain insufficiently explored. In this context, this study aimed to analyze these transcriptional changes and prioritize putative abdominal pain-relevant candidate genes from exploratory differentially expressed gene (DEG) sets. Gene expression data (GSE66824) were obtained from the Gene Expression Omnibus (GEO). Whole-blood gene expression profiles were analyzed from 14 IBS and 19 IBD patients, with samples collected before and after a 9-week RR-MBI. Exploratory DEG sets were identified using GEO2R outputs with nominal P < 0.05 and absolute fold-change magnitude (AFC) ≥ 1.2. Functional enrichment analyses were performed using DAVID. Protein-protein interaction (PPI) networks were constructed using STRING and visualized in Cytoscape. Putative abdominal pain-relevant candidate genes were prioritized from exploratory DEG sets within PPI/MCODE modules based on network position, matching module genes to the DisGeNET disease entry “pain”, and targeted pain-related literature annotation. (1) In IBD post-MBI, 649 exploratory DEGs were identified, with enrichment of neurotrophin and TGF-β signaling pathways; MAP3K7, SLC12A2, and FKBP5 were prioritized as candidate genes. (2) In IBS post-MBI, 175 exploratory DEGs were identified, with enrichment of glutamatergic synapse and calcium signaling pathways; network analysis highlighted NTRK2, FKBP5, and AR as candidate genes. (3) At baseline, 836 exploratory DEGs were identified, with enrichment in pathways including p53 signaling and NOD-like receptor signaling; notable prioritized candidate genes included TRAF6 and TNFSF11. Prioritized genes after RR-MBI and in the baseline comparison may represent putative abdominal pain-relevant candidate transcriptional signals in IBS and IBD. These exploratory findings require validation in independent cohorts with matched individual-level pain-related outcomes and functional studies.
Lin Z, Mo G, Wang Y, Lin S, Guo Q
The dual role of CCL20 in inflammatory disease: Maintenance of host defense and immunopathological balance.Review Pathology, research and practice | 2026-06-08
The chemokine, CCL20, is the only ligand of CCR6 and acts as a molecular switch in immune homeostasis, affecting both protective immunity and pathological inflammation through spatiotemporal regulation of CCR6⁺ leukocytes. CCL20 recruits Th17 cells, γδ T cells and ILC3s, forming synergistic antimicrobial networks with β-defensins and IgA to promote mucosal defense. Chronic CCL20 overexpression caused by NF-κB/MAPK signaling and epigenetic modification is responsible for self-perpetuating inflammation in rheumatoid arthritis, inflammatory bowel disease and psoriasis due to Th17-dominant feedback loops. CCL20 appears to have a role in organizing tertiary lymphoid structures and mediating gut-skin communication, which is affected by gut dysbiosis. Plasmonic nanoarrays and exosome profiling have enabled the discrimination of bioactive CCL20 isoforms with femtogram sensitivity, exposing the possibility for precision biomarker panels. Intelligent delivery systems, such as phase-responsive hydrogels and engineered probiotics, may enable tissue-specific therapeutic modulation. Challenges remain in the balancing of pathway inhibition with mucosal protection and trials of CCR6 antagonists have revealed risks of opportunistic infection. Future directions include dual-modality agents, AI-integrated multi-omics and circadian-timed interventions to preserve host defense during treatment for immunopathology.
Xu L, Xiao Y, Jiang Y, Deng J, Xie W, Luo Z, Wang Q, Zeng Z, Liu J
Targeting barrier integrity: Pseudoginsenoside RT2 ameliorates ulcerative colitis by driving epithelial renewal via the Wnt/β-catenin pathway.★ Phytomedicine : international journal of phytotherapy and phytopharmacology | 2026-06-05
Ulcerative colitis (UC) is a chronic, relapsing inflammatory bowel disease characterized by intestinal barrier dysfunction. Pseudoginsenoside RT2, an ocotillol-type ginsenoside widely present in Panax species, possesses unexplored therapeutic potential for UC. This study investigated the efficacy of RT2 against UC and its mechanisms of intestinal barrier protection by driving epithelial renewal. Anti‑UC effects of RT2 were assessed in lipopolysaccharide (LPS)‑stimulated Caco‑2 cells and dextran sulfate sodium (DSS)‑induced mice. Integrated transcriptomic and proteomic analyses were performed to identify key pathways in barrier restoration. Mechanistic validation was conducted using DSS‑induced intestinal organoids (encompassing all epithelial lineages) and LPS‑stimulated IEC-6 cells (non-transformed intestinal epithelial model). Effects on Wnt/β-catenin pathway were assessed with inhibitor ICG-001. In Caco‑2 cells, RT2 restored transepithelial electrical resistance (TEER), regulated cytokines and upregulated tight junction proteins (TJs). In UC mice, RT2 dose‑dependently ameliorated disease activity index (DAI), improved colon length and histopathology, increased anti‑inflammatory cytokines and reduced pro‑inflammatory cytokines. RT2 enhanced TJs and epithelial markers. Multi-omics analysis linked RT2’s benefits to Wnt/β-catenin pathway activation. In organoids, RT2 increased budding and Lgr5 expression. In IEC‑6 cells, RT2 restored TEER, promoted proliferation/migration, suppressed apoptosis and upregulated TJs and epithelial markers. Mechanistically, RT2 facilitated Wnt ligand-receptor binding, leading GSK-3β phosphorylation, disassembly of the destruction complex and β-catenin nuclear translocation. All effects were abolished by ICG‑001. RT2 attenuates UC by activating Wnt/β‑catenin pathway, thereby restoring intestinal barrier integrity via driving epithelial renewal, with efficacy comparable to the positive control drug SASP. RT2 represents a promising natural product candidate for UC treatment.
Li Z, Tan L, Wu J, Liu H, Geng X, Bu Y, Yue X, Wang Y, He X, Wang C
Elevated TFR1 is associated with inflammatory burden and ferroptosis in ulcerative colitis. Frontiers in medicine | 2026-06-03
Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by mucosal inflammation, oxidative stress, and iron metabolism dysregulation. Ferroptosis, an iron-dependent form of regulated cell death, may contribute to the pathogenesis of UC. Transferrin receptor 1 (TFR1), a key mediator of cellular iron uptake, links iron dysregulation to inflammation and ferroptosis; however, its clinical relevance in UC is not well defined. Serum samples were collected from 83 patients with active UC and 80 age- and sex-matched healthy controls. Disease activity was assessed using the modified Mayo score. Serum TFR1, inflammatory cytokine, coagulation indices, oxidative stress marker, and ferroptosis-related antioxidant levels were measured. Correlations and receiver operating characteristic (ROC) curve analyses were performed to evaluate the associations and diagnostic performance. Serum TFR1 levels were significantly higher in patients with UC than in controls (p < 0.001) and increased progressively with disease severity. TFR1 showed positive correlations with the Mayo score (r = 0.510), inflammatory markers, including C-reactive protein (CRP; r = 0.350), tumor necrosis factor-alpha (TNF-α; r = 0.406), interleukin-1 beta (IL-1β; r = 0.471), and interleukin-6 (IL-6; r = 0.432), coagulation parameters, including platelet count (r = 0.225), erythrocyte sedimentation rate (ESR; r = 0.451), and D-dimer (r = 0.447), serum iron (r = 0.267), and lipid peroxidation (r = 0.315), and negative correlations with the antioxidant defenses glutathione peroxidase 4 (GPX4; r = -0.236) and glutathione (GSH; r = -0.302). ROC analysis demonstrated that serum TFR1 distinguished patients with UC from controls, with an AUC of 0.795 at a cutoff of 4.8 ng/mL. Elevated serum TFR1 levels are associated with UC severity, systemic inflammation, oxidative stress, and ferroptosis-related imbalance. These findings suggest that TFR1 is a potential biomarker for UC activity and highlight iron-driven ferroptosis as a promising therapeutic target, providing novel clinical insights into disease monitoring and management.
He X, Ji J, Feng L, Chen G, Yao Y
Multi-layer transcriptomic analyses identify a mucin-associated epithelial program linked to innate inflammatory injury in ulcerative colitis. Frontiers in immunology | 2026-06-03
Epithelial barrier disruption and mucosal innate immune activation reinforce each other in ulcerative colitis (UC), yet the epithelial glycosylation programs linking mucus homeostasis to inflammatory tissue injury remain incompletely defined. Here, we integrated bulk, single-cell, and spatial transcriptomic analyses with functional validation to identify mucin-associated epithelial determinants relevant to UC. In the discovery cohort GSE107499, 15 dysregulated mucin-type O-glycosylation and mucin-associated genes were identified and were enriched mainly in O-glycan biosynthesis, glycosyltransferase activity, and Golgi-associated secretory functions. An integrative prioritization framework highlighted GALNT12 as the leading candidate. Low GALNT12 expression was associated with enrichment of TNFA signaling via NF-kB, inflammatory response, interferon gamma response, IL6-JAK-STAT3 signaling, and complement, together with higher infiltration scores for monocyte lineage cells, neutrophils, fibroblasts, and T-cell populations. At single-cell resolution, GALNT12 was concentrated in epithelial cells, particularly MUC2-positive epithelial cells. MUC2-positive epithelial cells with detectable GALNT12 expression showed broader inferred incoming and outgoing communication with surrounding epithelial, stromal, and immune populations and were enriched for proteostasis and secretory trafficking programs. Spatial transcriptomic analysis further identified GALNT12-high mucin-associated niches that co-localized with stronger goblet and mucin signatures and lower inflammatory scores. In HT29-19A cells, GALNT12 knockdown exacerbated TNF-α-induced LDH release, reduced OCLN and TJP1 expression, increased IL-8, IL-6, CCL2, IL-1β, and IL-18 production, and enhanced caspase-1 processing detected as cleaved caspase-1 p10 together with increased GSDMD-N formation under TNF-α stress. Collectively, these findings identify a GALNT12-centered mucin-associated epithelial program linked to epithelial barrier resilience and relatively restrained innate inflammatory injury at the barrier-immune interface in UC, while supporting a caspase-1/GSDMD-associated inflammatory injury phenotype under cytokine stress.
Huang J, He J, Li H, Chen R, Li P, Zhao J, Gao X
An orally deliverable Co3O4@MMT nanozyme platform for inflammatory bowel disease via ROS scavenging, barrier repair, and mucosal homeostasis regulation. Materials today. Bio | 2026-06-01
Inflammatory bowel disease (IBD) is a chronic gastrointestinal disorder characterized by a self-perpetuating pathological loop, where excessive reactive oxygen species (ROS) induce mucosal inflammation, which in turn drives further ROS production. This oxidative-inflammatory cycle leads to intestinal epithelial barrier disruption and gut microbiota dysbiosis. Current immunosuppressive therapies primarily target downstream inflammation, while fail to address the foundational oxidative stress and achieve complete mucosal healing. To bridge this gap, we developed an orally deliverable nanozyme platform by anchoring cobalt oxide (Co3O4) nanoparticles onto montmorillonite nanosheets (Co3O4@MMT). This design leverages the Co2+/Co3+ redox cycling within Co3O4 for efficient multi-enzymatic ROS scavenging. Furthermore, transcriptomic analysis and literature evidence suggest that the released Co2+ ions can activate the HIF-1α pathway-a key regulator of epithelial repair. The MMT component protects the nanozyme from gastrointestinal degradation and facilitates its electrostatic accumulation at inflamed colonic sites. In murine colitis models, oral Co3O4@MMT treatment effectively alleviated disease severity, suppressed inflammation, restored barrier integrity, and rebalanced gut microbiota. This work presents an integrated oral strategy that concurrently targets oxidative stress, inflammation, and barrier restoration, offering a comprehensive therapeutic approach for IBD.
Li Y, Zhou Q, She Y, Lu B, Wu M, Chen T, Ye P, Yu L, Liu W, Deng H
Butyrate-Producing Bacteria in Intestinal Disease Therapy: Potential and Challenges.Review Biotechnology journal | 2026-06
Butyrate-producing bacteria have emerged as keystone species whose metabolic activity orchestrates host-microbial homeostasis in the human gut. This review synthesizes current understanding of how these anaerobic Firmicutes, including Faecalibacterium prausnitzii, Roseburia spp., and Eubacterium rectale, function as key contributors to intestinal health through convergent mechanisms: serving as the primary energy source for colonocytes, enforcing mucosal hypoxia that excludes facultative pathogens, and modulating immunity via histone deacetylase inhibition and G-protein-coupled receptor signaling. We critically examine the translational trajectory of butyrogenic therapies across inflammatory bowel disease, colorectal cancer, and emerging applications in radiation injury, infection, and graft-versus-host disease. Despite compelling mechanistic rationale and consistent clinical associations linking butyrate-producer depletion with disease activity, therapeutic translation faces formidable bottlenecks: extreme oxygen sensitivity complicates manufacturing; cross-feeding networks necessitate ecological rather than monostrain approaches; and host context determines whether butyrate exerts protective or permissive effects. We evaluate cutting-edge strategies to overcome these barriers, including rationally designed consortia, precision prebiotics, phage-mediated niche engineering, synthetic biology approaches, and AI-guided personalization. By integrating mechanistic insight with translational pragmatism, this review outlines a path toward evidence-based butyrogenic therapies that may complement existing strategies for intestinal disease.
Zhang F, Zhang W, Ren X, Liu B, Zhou X
Global phenotypic similarity in inflammatory bowel disease: the Eastern Mediterranean region perspective.★ Journal of Crohn’s & colitis | 2026-06
Abstract not available.
Quraishi MN, Jess T, Al-Bawardy B
DNA From Neutrophil Extracellular Traps Restricts Group 3 Innate Lymphoid Cells Function in Intestinal Epithelial Repair via CCDC25. FASEB journal : official publication of the Federation of American Societies for Experimental Biology | 2026-06
Accumulation of neutrophil extracellular traps (NETs) in ulcerative colitis (UC) is associated with impaired intestinal epithelial barrier integrity. However, little is known about how NETs affect intestinal epithelial repair. This study sheds light on the molecular mechanisms through which excess NETs cause intestinal epithelial damage in UC mice. We found that UC mice had elevated levels of circulating cell-free DNA (cfDNA), mainly from NET byproducts (e.g., NET-DNA). NET-DNA in the intestine worsened UC symptoms, while DNase I treatment to eliminate it alleviated these symptoms. RNA-seq analysis revealed significant changes in IL-22 mRNA between wild-type and peptidylarginine deiminase 4 knockout (PAD4-/-) mice. Flow cytometry results indicated that NET-DNA mainly affected IL-22 secretion by group 3 innate lymphoid cells (ILC3s), while other forms of DNA had little influence on IL-22 expression. The IL-22+ILC3s ratio was restored in both DNase I-treated and PAD4-/- mice; moreover, levels of mucin, tight junction proteins, and Ki67 were significantly increased. Co-incubating ILC3s or the mouse lymphocyte cell line MNK3 with NET-DNA decreased IL-22 levels. ILC3s expressed the NET-DNA receptor coiled-coil domain containing protein 25 (CCDC25); however, NET-DNA did not affect IL-22 secretion in shCCDC25-MNK3 cells. Additionally, inhibiting ILK-HIF-1α proteins, downstream of CCDC25, increased IL-22 production in MNK3 cells. Finally, we established an in vitro culture system using MNK3 and Caco-2 cells. The supernatant from NET-DNA-treated MNK3 cells increased FITC-dextran permeability and reduced ZO-1 expression in Caco-2 cells. Thus, CCDC25 in ILC3s responds to NET-DNA by reducing IL-22 levels in UC mice, negatively impacting mucosal healing.
Xu B, Ke X, Xie X, Yi Q, Li C, Zhao M, Deng X, Wang Q, Chen H, Xu R
Therapeutics & Mechanisms (19 papers)
Comment on: Real-world outcomes of ustekinumab, vedolizumab, and tumor necrosis factor inhibitors in very-early-onset inflammatory bowel disease.Letter Journal of gastroenterology | 2026-06-19
Comparative efficacy and safety of risankizumab versus ustekinumab in moderate-to-severe Crohn’s disease: a systematic review and meta-analysis. Minerva gastroenterology | 2026-06-19
Risankizumab and ustekinumab are biologics targeting the interleukin-23 pathway through distinct mechanisms (selective p19 versus shared p40 inhibition). Both are key options for moderate-to-severe Crohn’s disease, but comparative evidence remains limited. We aimed to evaluate their relative efficacy and safety using direct and indirect evidence to inform treatment decisions. We searched major databases for randomized controlled trials (RCTs) in adults with moderate-to-severe Crohn’s disease comparing risankizumab or ustekinumab with placebo or each other. Random-effects models were used for pairwise meta-analyses, and a Bayesian network meta-analysis (NMA) integrated direct and indirect evidence. Treatments were ranked using the surface under the cumulative ranking curve (SUCRA). Nine RCTs (N.=4814) were included. Versus placebo, risankizumab significantly improved clinical remission (odds ratio [OR] 2.24, 95% CI: 1.73-2.91) and response (OR=2.70, 95% CI: 2.02-3.61). Ustekinumab also increased remission (OR=2.14, 95% CI: 1.68-2.73) and response (OR=2.16, 95% CI: 1.67-2.80). In the NMA, risankizumab ranked highest for remission (SUCRA 96.9%) and response (98.1%), while ustekinumab occupied intermediate positions. Both agents were well tolerated; risankizumab ranked more favorably for serious adverse events and serious infections, whereas ustekinumab ranked slightly higher for total adverse events. Risankizumab and ustekinumab were both effective and generally well tolerated in moderate-to-severe Crohn’s disease. Risankizumab showed a more favorable efficacy pattern for remission and response and ranked more favorably for serious adverse events, whereas overall safety profiles were otherwise broadly comparable. These findings support treatment selection according to clinical priorities.
Moon S, Choi YJ, Shin S
Fulminant Eosinophilic Myocarditis After Sequential Biologic Therapy in Ulcerative Colitis.Case report JACC. Case reports | 2026-06-18
Eosinophilic myocarditis has heterogeneous presentations and may cause fulminant cardiogenic shock. A 35-year-old man with ulcerative colitis and eosinophilia developed cardiogenic shock after sequential biologic therapy (most recently vedolizumab) and corticosteroid withdrawal. He rapidly deteriorated with severe biventricular dysfunction (left ventricular ejection fraction 10%) and hypereosinophilia (eosinophil count 2,154/μL). Coronary angiography showed no obstructive disease, and cardiac magnetic resonance suggested diffuse myocardial involvement. Endomyocardial biopsy confirmed eosinophilic myocarditis. He required veno-arterial extracorporeal membrane oxygenation and high-dose intravenous methylprednisolone. Recurrent eosinophilia during tapering prompted use of mepolizumab, followed by recovery of left ventricular function. Biologic exposure with corticosteroid withdrawal was temporally associated with systemic eosinophilic activation, and histologic confirmation by biopsy enabled escalation to targeted therapy. In patients with inflammatory bowel disease receiving biologics, hypereosinophilia with acute heart failure should prompt evaluation for eosinophilic myocarditis. Early biopsy may enable timely escalation to targeted immunomodulatory therapy.
Lee J, Kim D, Hong D, Cha JH, Noeul K, Kim JS, Yang JH, Choi JO
Tibetan medicine Siwei Zhixie Mutang Powder ameliorates ulcerative colitis by suppressing JAK2/STAT3 and NF-κB signaling. Journal of ethnopharmacology | 2026-06-18
Siwei Zhixie Mutang Powder (SZMP) is a traditional Tibetan herbal formula widely used for gastrointestinal disorders, including enteritis, colitis, abdominal pain, diarrhea, and dysentery. Since ulcerative colitis (UC) is a chronic inflammatory disorder of the colon within the broader spectrum of intestinal inflammatory diseases, the traditional use of SZMP provides an ethnopharmacological basis for investigating its effects in experimental colitis. However, its key bioactive constituents and underlying molecular mechanisms remain poorly defined. This study aimed to identify the principal active compounds, potential targets, and molecular mechanisms by which SZMP exerts protective effects against DSS-induced ulcerative colitis. An integrative strategy combining UPLC-MS/MS analysis, network pharmacology, transcriptomics, molecular docking, molecular dynamics simulation (MD), microscale thermophoresis (MST), and in vivo experimental validation was established. A DSS-induced ulcerative colitis mouse model was used to evaluate disease activity, histopathological injury, inflammatory responses, apoptosis-related changes, and the activation status of the JAK2/STAT3 and NF-κB signaling pathways. UPLC-MS/MS identified 40 major constituents in SZMP, and 132 potential bioactive compounds with 913 predicted targets were retained after SwissADME screening. Integrated network pharmacology and transcriptomics revealed that SZMP mainly regulated inflammation- and apoptosis-related processes, particularly the JAK-STAT and NF-κB pathways. In DSS-induced colitis mice, SZMP alleviated disease symptoms, colonic injury, inflammatory cytokine overproduction, and excessive apoptosis, while inhibiting JAK2/STAT3 and NF-κB activation. UPLC-MS/MS quantification showed low levels of aristolochic acid A and strychnine in SZMP, and no obvious toxicity-related signs or major organ abnormalities were observed after 7 days of administration. Docking, MD simulation, and MST further supported a stable and direct interaction between (+)-catechin and TNFR1. SZMP protected against DSS-induced ulcerative colitis, possibly through multi-constituent regulation of inflammation- and apoptosis-related targets, mainly involving the JAK2/STAT3 and NF-κB pathways. MD simulation and MST further showed that (+)-catechin directly bound to TNFR1, suggesting its potential role in modulating the TNF/TNFR1-NF-κB inflammatory axis. In addition, UPLC-MS/MS quantification and 7-day safety evaluation indicated low exposure levels of aristolochic acid A and strychnine, with no obvious toxicity-related signs or major organ abnormalities observed under the experimental conditions. These findings provide experimental evidence for the pharmacodynamic basis, mechanism, and short-term safety profile of SZMP in UC intervention.
Yue G, Xu C, Liu H, Zhu Z, Chen Y, Jiang G, Liu X, Dou J, Mo G, Ren Q
Sustained Treatment Success With Ustekinumab in Symptomatic Stricturing Crohn’s Disease: A Retrospective Single-Arm Observational Cohort Study. MedComm | 2026-06-17
Despite being a common complication of Crohn’s disease (CD), evidence regarding the use of ustekinumab (UST) for treating symptomatic strictures in China remains limited. This study evaluated the effectiveness of UST in this population and identified the predictors of successful therapy. This cohort study enrolled adults with CD initiating UST therapy for symptomatic strictures confirmed by endoscopy or imaging. The primary outcome at Week 52 was continued UST therapy without prohibited adjunctive treatments. A clinical prediction model was developed, and its performance was evaluated for identifying baseline factors associated with treatment success. Of the 73 patients screened between June 2022 and April 2024, 54 were included. At Week 52, 44 (81.5%) achieved treatment success, with most demonstrating improvements in obstructive symptom score, CD Activity Index (CDAI), endoscopic and computed tomography enterography (CTE) findings, and biochemical parameters. Nonsmoking status and C-reactive protein (CRP) levels predicted treatment success, with the model demonstrating 86.4% discriminative ability. No severe adverse events were reported, except for one case of leukemia (2%) and two cases of serious infections (4%). The study highlighted that UST effectively alleviated intestinal strictures in CD, with most patients achieving symptom remission, improved stricture morphology, and reduced inflammation.
Liu J, Hu W, Li S, Hu S, Jiang D, Chen Y
Bifenthrin exacerbates ulcerative colitis via immunotoxicity: network toxicology and experimental validation reveal novel therapeutic targets. BMC pharmacology & toxicology | 2026-06-16
Bifenthrin (BF) is a widely used pyrethroid insecticide and is recognized as an endocrine-disrupting chemical (EDC). Accumulating evidence indicates that long-term exposure to BF can induce a variety of adverse health outcomes. However, its potential role in the pathogenesis of ulcerative colitis (UC) remains elusive. In this study, we integrated data from multiple databases-including the Comparative Toxicogenomics Database (CTD), TargetNet, GeneCards, SwissTargetPrediction, and STITCH-to predict potential molecular targets of BF. UC-associated genes were compiled from GeneCards, Online Mendelian Inheritance in Man (OMIM), DisGeNET, Therapeutic Target Database (TTD), and DrugBank. Candidate targets were identified by intersecting predicted BF targets with UC-related genes, followed by functional enrichment analysis using DAVID. The STRING database and Cytoscape software were employed to construct protein-protein interaction (PPI) networks and screen for hub genes. A diagnostic model based on these hub genes was established and validated using the GSE47908 and GSE13367 datasets. Additionally, immune infiltration analysis was performed to compare the UC group with controls, identifying immune cell types significantly associated with the target genes. Molecular docking simulations via AutoDock Vina were conducted to evaluate the binding affinities between BF and the five hub proteins. Functional analysis revealed that the candidate genes were primarily enriched in pathways related to oxidative stress and inflammatory responses. Five core hub genes-BCL2, TP53, TNF, IL6, and PTGS2-were consistently identified across all analytical platforms. In vitro experiments demonstrated that BF exposure significantly exacerbated colonic inflammation by downregulating anti-inflammatory/apoptotic genes (BCL2, TP53) and upregulating pro-inflammatory markers (IL6, TNF, PTGS2). Collectively, our findings suggest that bifenthrin may promote colorectal inflammation by dysregulating key genes and modulation of the pro-inflammatory immune microenvironment, thus providing novel insights into the environmental etiology of UC.
Wang L, Zhang W, Kang Y, Li Y
An inverse probability of treatment weighted comparison between vedolizumab, ustekinumab, and tofacitinib in anti-TNF-experienced ulcerative colitis patients. Therapeutic advances in gastroenterology | 2026-06-15
Biologics and small-molecule therapies are widely used for ulcerative colitis (UC), but their comparative effectiveness in anti-tumor necrosis factor (TNF)-exposed patients is unclear. To compare the effectiveness and safety of vedolizumab, ustekinumab, and tofacitinib in anti-TNF-experienced patients with UC. Multicenter retrospective observational cohort study. A multicenter retrospective cohort of anti-TNF-experienced UC patients treated with vedolizumab (n = 260), tofacitinib (n = 149), or ustekinumab (n = 193) was analyzed. Partial Mayo Score (pMayo), endoscopic remission, and biomarker response were assessed at baseline, 12, 24, and 52 weeks, respectively. Inverse Probability of Treatment Weighting (IPTW) was applied to balance baseline characteristics, and longitudinal changes were analyzed using repeated-measures general linear models with post hoc corrections. After IPTW adjustment, at week 52, clinical remission was highest with tofacitinib compared with ustekinumab (p < 0.001) and vedolizumab (p = 0.002). Steroid-free clinical remission showed a similar pattern (tofacitinib vs ustekinumab: p = 0.006; tofacitinib vs vedolizumab: p < 0.001). No significant differences in biochemical remission were found across groups at week 52 (p = 0.931). Endoscopic remission favored vedolizumab over ustekinumab and tofacitinib (p < 0.001). Subgroup analyses revealed superior tofacitinib performance in extensive colitis and in patients with ⩾2 prior biologic classes (vs vedolizumab: p = 0.089; vs ustekinumab: p < 0.001). Adverse events were infrequent and similar across groups. In anti-TNF-experienced UC patients, tofacitinib was associated with higher long-term clinical and steroid-free remission rates, ustekinumab showed intermediate effectiveness with a favorable safety profile, while vedolizumab was associated with higher endoscopic remission. These findings may help inform individualized, outcome-oriented treatment strategies, but they should be interpreted with caution and confirmed in prospective head-to-head studies.
Tursi A, Pasta A, Elisei W, Barberio B, Bertin L, Mocci G, Maconi G, Gravina AG, Pellegrino R, Bodini G
Fever of Unknown Origin as an Isolated Manifestation of Ulcerative Colitis Despite Clinical and Radiographic Remission: A Case Report.Case report Cureus | 2026-06-15
Fever is a recognized manifestation of active ulcerative colitis (UC); however, isolated fever in the absence of GI symptoms or objective evidence of active colonic inflammation is exceedingly uncommon. The diagnostic challenge is amplified in immunocompromised patients receiving biologic therapy, in whom occult infection must be rigorously excluded. We present a 68-year-old woman with a history of well-controlled HIV infection and recently diagnosed UC who was initiated on vedolizumab, mesalamine, and a prednisone taper in the outpatient setting. She presented with persistent daily fevers and initial concern for an infectious etiology of pyrexia. Ulcerative colitis appeared to be well treated, with outpatient CT demonstrating resolution of colitis, and the patient denied diarrhea, abdominal pain, hematochezia, or other symptoms suggestive of active disease. An extensive infectious workup, including blood cultures, viral studies, fungal biomarkers, Lyme disease testing, tick-borne testing, and autoimmune serologies, was negative. During the laboratory evaluation, thrombocytopenia, markedly elevated inflammatory markers, and elevated D-dimer levels were noted. Despite a comprehensive multidisciplinary evaluation, no infectious, malignant, thrombotic, or rheumatologic etiology was identified. Throughout her hospital course, the patient developed sequelae of a severe inflammatory response, including atrial fibrillation. The patient’s fevers were ultimately attributed to an atypical systemic inflammatory manifestation of UC. This case highlights a rare presentation of UC manifesting predominantly as fever of unknown origin (FUO) despite apparent clinical and radiographic remission. Clinicians should recognize that significant systemic inflammation may occur even in the absence of overt GI disease activity after exclusion of alternative causes.
Memon M
Comparative Real-World Effectiveness of Anti-TNF, Ustekinumab and Vedolizumab in Crohn’s Disease Over 24 Months: A Pooled Analysis From the Prospective UMBRELLA-IBD Registry in Germany.★ Alimentary pharmacology & therapeutics | 2026-06-15
Real-world evidence is needed to understand the comparative effectiveness of biologics in Crohn’s disease (CD) under routine-care conditions. We conducted a pooled analysis of individual patient data from prospective German CD registries (BioCrohn, RUN-CD, VEDO-IBD) in the UMBRELLA-IBD data warehouse. We included 1567 adults with CD who initiated anti-TNF therapy (adalimumab or infliximab), ustekinumab or vedolizumab. The main outcome was clinical remission (CR) at 24 months (HBI ≤ 4). Additional outcomes included HBI, EQ-VAS and treatment persistence over time. Between-group comparisons used propensity-score-based inverse probability of treatment weighting. After weighting, CR following induction was observed in a slightly higher proportion of patients initiating anti-TNF therapy (74.5%) than ustekinumab (69.4%) or vedolizumab (65.3%) (p = 0.035). Clinical response was 77.9%, 73.5% and 67.8%, respectively (p = 0.015). At 24 months, CR rates were similar in magnitude (anti-TNF, 53.4%; ustekinumab, 63.5%; vedolizumab, 58.7%) but were higher with ustekinumab than anti-TNF (p = 0.004). Over 24 months, treatment persistence differed (log-rank p < 0.001) and was highest for adalimumab (81.4%), lowest for infliximab (66.6%), and intermediate for ustekinumab (78.6%) and vedolizumab (76.9%). HBI decreased and remained low, and EQ-VAS improved, with no relevant between-group differences. Overall effectiveness in CD was high, with only small differences between biologic therapies. At the end of induction, CR was slightly higher with anti-TNF therapy than with vedolizumab, whereas at 24 months it was slightly higher with ustekinumab than with anti-TNF. Marked differences in treatment persistence among the evaluated biologics suggest that persistence as an endpoint is not fully explained by CR alone.
Bokemeyer A, Tran F, Plachta-Danielzik S, Gilman E, Wenske T, Gaskins M, Schreiber S, Bokemeyer B
Real-World Outcomes of Upadacitinib Versus Risankizumab Among Anti-TNF Exposed Patients with Crohn’s Disease.★ Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association | 2026-06-15
The optimal sequencing of therapy following anti-tumor necrosis factor (TNF) inhibitor failure in Crohn’s disease (CD) remains uncertain. We compared the effectiveness of upadacitinib (UPA) versus risankizumab (RSZ) in patients with active luminal CD previously exposed to anti-TNF therapies. We conducted a retrospective single-center cohort study of adults with CD initiating UPA or RSZ (January 2022- November 2025). The primary outcome was post-induction (week 12-24) corticosteroid-free (CSF) clinical remission. Secondary outcomes included CSF clinical remission at week 52, combined CSF clinical and biochemical remission post-induction and at week 52, biomarker and endoscopic changes, treatment persistence, and adverse events. Inverse probability of treatment weighting with additional adjustment for baseline disease severity was used to account for baseline differences; sensitivity analyses included weight truncation and overlap weighting. Among 175 anti-TNF-exposed patients (RSZ n=115; UPA n=60), unadjusted post-induction CSF clinical remission occurred in 60% (33/55) of UPA-treated patients and 55% (60/109) of RSZ-treated patients. After IPTW and disease severity adjustment, there was no significant difference in post-induction CSF clinical remission (adjusted odds ratio [aOR] 1.05; 95% confidence interval [CI] 0.46-2.41) or combined CSF clinical and biochemical remission (aOR 1.14; 95% CI 0.48-2.72). At week 52, remission estimates were limited by reduced follow-up but were also not significantly different after adjustment. Treatment persistence and serious and infectious adverse event rates were similar between groups after adjustment. In anti-TNF-exposed patients with active luminal CD, UPA and RSZ achieved similar post-induction remission after adjustment for baseline differences.
McShane C, Olivera PA, Candido K, Milgrom R, Borowski K, Kim J, Stempak J, Nguyen GC, Tandon P, Weizman AV
Bridging the gap between guidelines and practice: comparative effectiveness of ustekinumab and vedolizumab in Crohn’s disease. Proceedings (Baylor University. Medical Center) | 2026-06-15
Comparison of Tacrolimus and Infliximab for Acute Severe Ulcerative Colitis in Hospitalized Adults: A Retrospective Study. Journal of digestive diseases | 2026-06-15
Comparative data on infliximab (IFX) and tacrolimus as salvage therapies for intravenous glucocorticoid (ivGC)-refractory acute severe ulcerative colitis (ASUC) are limited. We aimed to evaluate the effectiveness and safety of IFX versus tacrolimus in hospitalized patients with ivGC-refractory ASUC. This retrospective study was conducted between 2017 and 2024 at a tertiary medical center, including inpatients with ASUC who failed ivGC and received IFX or tacrolimus. The primary outcome was colectomy-free clinical response at discharge. Thirty-seven patients received IFX (median age 27 years; 32.4% males), and 24 received tacrolimus (median age 32 years; 41.7% males). Compared with the patients who received IFX, those receiving tacrolimus had a longer disease duration (4 years vs. 1 year, p = 0.031) and a higher rate of prior exposure to advanced therapy (anti-tumor necrosis factor agent: 58.3% vs. 2.7%, p = 1.05 × 10-6; Janus kinase inhibitors: 20.8% vs. 0%, p = 0.007). The length of hospitalization was significantly longer among those receiving tacrolimus (median 19.5 days vs. 11.0 days, p = 0.019). Colectomy-free clinical response rate at discharge (81.1% vs. 83.3%, multivariate analysis p = 0.956) and total colectomy rate in the following year (12.5% vs. 14.3%, p = 0.851) did not significantly differ between the IFX and tacrolimus groups. Safety profile during hospitalization was comparable between groups. In ivGC-refractory ASUC cases, IFX and tacrolimus showed comparable effectiveness and safety. Similar outcomes were observed despite a more treatment-refractory profile in the tacrolimus group. These findings support the use of either agent as a feasible salvage option in this clinical setting.
Sror N, Tamir-Degabli N, Shaham D, Rozenfeld A, Leibovitzh H, Hirsch A, Thurm T, Ron Y, Fishman S, Maharshak N
Macrophage plasticity as a therapeutic target in inflammatory bowel disease: Immunomodulatory and regenerative strategies.Review International immunopharmacology | 2026-06-15
Inflammatory bowel disease (IBD), which mainly includes Crohn’s disease and ulcerative colitis, is a chronic inflammatory disorder of the gastrointestinal tract characterized by recurrent episodes of intestinal inflammation. The development of IBD is influenced by multiple factors, including genetic predisposition, intestinal dysbiosis, epithelial barrier impairment, and abnormal immune activation. Among innate immune cells, macrophages are key regulators of intestinal immune homeostasis and are involved in inflammatory responses, tissue remodeling, and mucosal repair. Their ability to adopt different functional states in response to local environmental signals has made them an important focus of current therapeutic research in IBD. Traditionally, macrophages have been classified into pro-inflammatory M1 and anti-inflammatory M2 phenotypes. However, recent findings from single-cell transcriptomic and spatial analyses suggest that intestinal macrophages represent a far more diverse and dynamic population than this simplified classification implies. Multiple macrophage subsets with inflammatory, regulatory, reparative, and fibrosis-associated functions coexist within the intestinal microenvironment and contribute differently to disease progression and tissue healing. These observations highlight the importance of developing more selective and targeted macrophage-based therapeutic approaches. In this review, we discuss the current understanding of macrophage plasticity and its role in the pathogenesis of IBD. Particular attention is given to newer macrophage-targeted therapeutic strategies, including adoptive macrophage transfer, engineered macrophages, receptor-targeted therapies, nanoparticle-based delivery systems, microbiome modulation, microbial metabolite regulation, gene-editing approaches, organoid technologies, and biomaterial-assisted platforms. We also examine the contribution of macrophages to epithelial regeneration, mucosal healing, fibrosis, and intestinal tissue remodeling. In addition, we address several major challenges that currently limit the clinical translation of macrophage-targeted therapies. A better understanding of macrophage biology, together with continued advances in immunology, regenerative medicine, microbiome research, and biomaterials science, may support the development of more precise and personalized therapeutic strategies for patients with IBD.
Nasimi F, Ashtari S, Moafi S, Baneshi F, Feizollah R, Samadi A
Correlation of Omentin-1 with Disease Extent and Therapeutic Response to Infliximab in Ulcerative Colitis. Journal of inflammation research | 2026-06-11
Ulcerative colitis (UC) is classified by both activity and extent. Accumulating evidence suggests that disease extent is an independent factor in determining poor prognosis. However, there is a significant lack of blood biomarkers that mirror lesion reach, clinicians still rely on repeated endoscopy to determine disease activity and mucosal healing. Omentin-1 is an adipokine secreted mainly by visceral adipose tissue and intestinal goblet cells that has been reported to exert anti-inflammatory and epithelial-barrier-enhancing effects. Therefore, we hypothesized that serum omentin-1 correlates with disease extent and predicts primary response to infliximab (IFX). Consecutive UC patients (n = 126) were enrolled and stratified by Montreal classification into distal (E1/E2, n = 84) or extensive (E3, n = 42) disease. Serum omentin-1 was quantified by ELISA. Clinical activity (partial Mayo) and endoscopic activity (MES) were recorded. Among 36 subjects who received standard IFX induction, response was assessed at week 14. Among the 126 UC patients, serum omentin-1 levels were significantly lower in extensive than distal colitis [median: 48.60 (38.28-67.35) ng/mL vs 62.70 (58.48-73.88) ng/mL, p < 0.01]. By controlling for clinical and endoscopic activity scores between groups, we found that serum omentin-1 levels differed between patients with different UC disease extents at the same level of disease activity, suggesting that serum omentin-1 can effectively predict the disease extent of UC independently of disease activity. In the IFX cohort (n = 36), responders (n = 23) exhibited higher baseline serum omentin-1 than non-responders. Extent-stratified analysis revealed that the discriminative capacity was confined to extensive colitis, with no significant predictive value in distal disease. Serum omentin-1 quantifies UC extent independently of activity and predicts IFX response specifically in extensive colitis, offering a blood-based tool to map disease extent and guide biologic therapy. This finding may reduce the reliance on repeated colonoscopy and support therapeutic stratification in extensive disease.
Chen C, Wang J, Wang T, Zhou Z, Gao C, Pan Y, He C
Safety evaluation of subcutaneous and intravenous administration of infliximab: a real-world study based on the FAERS database. Frontiers in medicine | 2026-06-01
Inflammatory Bowel Disease (IBD) is characterized by recurrent flare-ups, significantly impairing patients’ long-term quality of life and increasing the risk of complications. As the first chimeric monoclonal antibody targeting tumor necrosis factor-alpha (TNF-α), infliximab blocks TNF-α-mediated inflammatory cascades and has become an important therapeutic agent for moderate-to-severe IBD. Although clinical trials have highlighted its safety and efficacy, real-world data on adverse events (AEs) associated with different administration routes remains limited. This study aims to analyze the U. S. Food and Drug Administration’s Adverse Event Reporting System (FAERS) to compare the spectrum and time-to-onset of infliximab-related AEs across different administration routes, following the READUS-PV guidelines. Data from the FAERS database were analyzed using discriminant and stratified analytical methods, and reporting odds ratio (ROR) methods for comparative analysis, and the Weibull distribution for the time to onset of adverse reaction events analysis. The study examined data from the first quarter of 2014 through the first quarter of 2025 to analyze adverse event signals and the time of occurrence between intravenous and subcutaneous infliximab administration. A total of 178,925 adverse reaction reports associated with infliximab were identified. Among these, 5,144 events were linked to intravenous administration, while 1,084 events were related to subcutaneous administration. The analysis revealed that infection-related adverse reactions were common with both different administration routes of infliximab. Notably, reports of infusion-related reactions were more frequently associated with intravenous administration, while delayed hypersensitivity reactions involving musculoskeletal and connective tissue disorders were more prominently reported in association with subcutaneous administration. Additionally, Weibull distribution analysis indicated a median onset time of 436.5 days for intravenous administration and 376 days for subcutaneous administration. Both routes exhibited early failure signals, suggesting a gradually decreasing risk of AEs over time. AEs and the time of onset vary across different administration routes of infliximab. Consequently, clinicians should consider these differences when selecting the administration route to balance therapeutic efficacy with the risk of adverse reactions.
Zheng X, Xie M, Luo H, Cai J, Xu R, Ling T
Severe cerebellitis as a manifestation of infliximab-associated overlap of neurosarcoidosis and myelin oligodendrocyte glycoprotein antibody-associated disease - case report.Case report Frontiers in immunology | 2026-06-01
Tumor necrosis factor-α (TNF-α) inhibitors such as infliximab are widely used in autoimmune disorders. Paradoxical inflammatory reactions including systemic sarcoidosis and neurosarcoidosis are increasingly recognized but remain rare. We report a 56-year-old male with ulcerative colitis under infliximab therapy presenting with acute dysarthria and gait instability. Neurological examination revealed truncal ataxia. Brain and spinal MRI were normal. Cerebrospinal fluid analysis showed lymphocytic pleocytosis, reduced glucose, increased lactate, and elevated protein with marked blood-brain barrier disruption. Sarcoidosis-associated markers (neopterin, ACE, IL-2 receptor) were elevated. Pulmonary CT and lymph node biopsy confirmed systemic sarcoidosis. Moreover, MOG-antibodies were detected in both serum and CSF. After initial empirical anti-infective therapy, high-dose corticosteroids were initiated, resulting in full recovery. Infliximab therapy was discontinued. This case demonstrates infliximab-associated overlapping autoimmunity with sarcoidosis, probable neurosarcoidosis and MOGAD presenting with acute cerebellitis. Clinicians should consider neurosarcoidosis and MOGAD in patients on TNF-α-inhibitors presenting with neurological deficits, even in the absence of radiological findings. Early discontinuation of the triggering agent and timely corticosteroid therapy are essential for favorable outcomes.
Hütter G, Winkelhausen M, Tönges L, Gold R, Faissner S
Induction and Prolonged Induction With Mirikizumab in Ulcerative Colitis-A Prospective, Real-World Study From the Sicilian Network for Inflammatory Bowel Disease (SN-IBD).★ United European gastroenterology journal | 2026-06
Mirikizumab (MIRI), an IgG4 monoclonal antibody targeting IL-23 p19, was recently licensed for ulcerative colitis (UC). Most available data come from the pivotal trials, but real-life data are scant. We aimed to evaluate the effectiveness and safety of MIRI in a real-world setting. UC patients from 12 centres of the SN-IBD were prospectively enrolled. The primary endpoints were clinical response, steroid-free remission (SFR), and reduction of urgency at week 12 and at week 24. As secondary endpoint, the need for prolonged induction was considered. All patients received 3 infusions at monthly intervals of 300 mg MIRI; in case of inadequate response, the induction period was prolonged. Urgency was determined by means of the Urgency Numerical Rating Scale (UNRS). One hundred and five patients were included. Previous failures to 2 or more lines of advanced therapies were present in 74% of patients. At week 12, 24% of patients achieved a clinical response and 53% achieved SFR. At week 24 (n = 71), the rates were 20% and 68%, respectively. The median urgency score decreased from 6 at baseline to 2 at week 12 and to 1 at week 24 (p < 0.001, both). Prolonged induction was necessary to half of patients. Adverse events were reported in 5% of patients. Treatment failures occurred in 14 patients (13%). Our real-life study confirmed the short-term effectiveness and safety of MIRI in patients with UC especially in relieving bowel urgency. The flexible induction schedule allows an additional gain in response and remission.
Costantino G, Viola A, Iuculano A, Macaluso FS, Voti RL, Cappello M, Antoci C, Ferracane C, Sciuto M, Catarella D
Histologic and combined histologic-endoscopic outcomes with mirikizumab in Crohn’s disease: VIVID-1 trial results.RCT★ Journal of Crohn’s & colitis | 2026-06
Evaluation of microscopic inflammation is an emerging therapeutic target of Crohn’s disease. The completed VIVID-1 trial evaluated histologic and combined histologic-endoscopic outcomes for mirikizumab relative to placebo and ustekinumab in moderately-to-severely active Crohn’s disease. Two specimens from each of five intestinal segments (one ileal, four colonic) were obtained from the edge of ulcers, or the most inflamed mucosa at screening, and weeks (W)12 and 52. Histologic response was defined as the absence of epithelial neutrophils and epithelial damage, erosions and ulceration or ≥50% decrease in either the active Robarts Histopathology Index or the active Global Histologic Disease Activity Score, and was prespecified. Histologic remission was defined as absence of mucosal neutrophils, no epithelial damage, and no erosions and ulcers and was a prespecified endpoint. Post-hoc analyses included subgroup analyses, the proportions of patients achieving combined histologic-endoscopic outcomes, the agreement between histologic outcomes and endoscopic or clinical outcomes, segmental analyses, the assessment of cut-off points for fecal calprotectin, and the association between W12 histologic outcomes and selected W52 outcomes. At W12, mirikizumab was superior to placebo for histologic response (P < .0001) and histologic remission (P = .001), with similar rates to ustekinumab (P = .58 and P = .44, respectively). At W52, mirikizumab-treated patients showed greater histologic response (P = .008) compared to ustekinumab, especially in patients who previously failed biologic therapies (P = .006). Combined histologic-endoscopic response at W52 was numerically higher for mirikizumab (P = .06) and reached statistical significance among biologic-failed patients (P = .02); however, combined remission rates were comparable across treatment arms. Mirikizumab was superior to placebo in achievement of all histology-based endpoints. Mirikizumab showed higher rates compared to ustekinumab for achievement of histologic response at W52. Early histologic response among endoscopic non-responders was associated with 1-year endoscopic outcomes. ClinicalTrials.gov, NCT03926130.
Jairath V, Magro F, Protic M, De Hertogh G, Harpaz N, Hisamatsu T, D’Haens G, Pai R, Yu G, Morris N
Practical considerations for empirical Bayes estimation using a pharmacokinetic/pharmacodynamic model developed from summary-level data of ustekinumab therapy in Crohn’s disease. The Journal of pharmacy and pharmacology | 2026-06
This study aimed to develop a pharmacokinetic/pharmacodynamic model using summary-level data (SLD-PK/PD model) for ustekinumab in Crohn’s disease and to propose practical considerations and an operating framework for empirical Bayes estimation (EBE) when individual patient data (IPD) models are unavailable. An SLD-PK/PD model was constructed using arm-level Crohn’s Disease Activity Index (CDAI) data from phase IIb/III trials. To evaluate EBE performance, simulated IPD (simIPD) was generated using a reported IPD-PK/PD model. Pseudo-SLD was derived from simIPD to refit the SLD-PK/PD model. EBE was performed at Week 8 to predict CDAI up to Week 20. Because individual-level variability is not identifiable from SLD, uncertainty was propagated using a prespecified σ2 grid and ω2 scaling, with η-shrinkage-guided bounds. Based on the variance-range framework, patients were classified as consistently predicted remission (6.9%), consistently predicted non-remission (66.2%), or indeterminate (26.9%). Predictive accuracy varied across σ2 assumptions, demonstrating the practical impact of variance specification. Although EBE using an SLD-PK/PD model is practically useful when IPD-PK/PD models are unavailable, predictions depend on variance assumptions. Therefore, σ2 and ω2 should be treated as uncertainty ranges, and decision stability should be evaluated across these ranges to ensure robust clinical applications.
Kimura K, Yoshida A
Microbiome & Immunology (18 papers)
Habitual Ultra-processed Food Intake Is Associated with Gut Dysbiosis and Pro-inflammatory Metabolite Profiles in Korean Patients with IBD. Digestive diseases and sciences | 2026-06-19
Ultra-processed food (UPF) is increasingly consumed worldwide and may influence gut microbial ecology relevant to inflammatory bowel disease (IBD). However, patient-level multi-omics data remains scarce. We investigated whether habitual UPF intake is associated with specific microbiota and metabolite profiles in Korean patients with IBD. Dietary intake was assessed using a validated food frequency questionnaire, and food was categorized by the NOVA system. UPF intake was expressed as percent of energy, and 313 patients were stratified into UPF low (Q1-Q2) and UPF high (Q3-Q4). Fecal samples of 174 patients underwent 16S rRNA sequencing and untargeted metabolomics. Microbiome differences were tested using PERMANOVA for beta-diversity and Mann-Whitney U tests for taxa. Differential metabolites were defined by p < 0.05 and |fold change|≥ 1.5, followed by Reactome enrichment with FDR correction. Correlations among microbiota, metabolites, and UPF subgroups were examined using Spearman tests with Benjamini-Hochberg adjustment. Associations between UPF intake and clinical characteristics were analyzed using Spearman tests, η2 from ANOVA and point-biserial correlation. Microbial beta-diversity differed significantly between UPF low and UPF high participants. UPF high participants showed expansion of pro-inflammatory pathobionts (Escherichia-Shigella, Proteus, Parasutterella, Enterococcus, Fusobacterium, and Clostridium innocuum group) and depletion of anti-inflammatory commensals (Faecalibacterium, Butyricicoccus, Lachnospiraceae ND3007 group, and Bifidobacterium). Metabolomic profiling revealed enrichment of inflammatory pathways (phospholipid metabolism, eNOS/NO signaling, mitochondrial β-oxidation, FMO3-mediated TMA to TMAO, tryptophan catabolism) and reduction of anti-inflammatory metabolites (AHR ligands, BAAT-conjugated bile acids). Integrated analyses demonstrated significant correlations between dysbiotic taxa and inflammatory metabolites. Among NOVA-defined UPF subgroups, sugar-sweetened beverages, ready-to-eat dishes, and packaged snacks and confectioneries showed the strongest associations with these adverse signatures. Analysis of clinical characteristics showed trends between total UPF intake and inflammatory markers (WBC, CRP, fecal calprotectin), and association with upper gastrointestinal tract involvement in patients with CD. Subgroup analysis showed that sugar-sweetened beverage intake was significantly associated with CRP elevation and upper gastrointestinal involvement in patients with CD. In IBD, higher UPF intake, particularly from specific NOVA-defined subgroups, is associated with gut dysbiosis and a pro-inflammatory metabolome, which in turn correlates with unfavorable clinical characteristics. These findings provide patient-based multi-omics evidence and underscore clinically relevant dietary targets for IBD management.
Shon WJ, Kim KA, Kim JS, Kim BG, Im JP, Lee HJ, Kim SH, Kim JW, Kang HW, Kim KW
Tea and digestive system health: integrating gut microbiota-involved ADME and personalized nutrition for gastrointestinal disorders intervention.Review Critical reviews in food science and nutrition | 2026-06-19
The global burden of digestive diseases is escalating, marked by rising incidence and severity. Tea, a widely consumed beverage rich in polyphenols, offers a promising dietary intervention due to its demonstrated capacity to modulate gut microbiota, suppress inflammation, and enhance gastrointestinal barrier function. This review provides a systematic integration of the ADME characteristics of key tea compounds with their complex interplay with the gut microbiome, underscoring the central role of microbial biotransformation in mediating the health benefits of tea. We critically examine the specific protective mechanisms of tea against prevalent gastrointestinal disorders, including gastritis, gastric ulcers, inflammatory bowel disease, irritable bowel syndrome, constipation, and diarrhea. A major focus is placed on the pivotal impact of interindividual variability, shaped by host factors and distinct gut microbial metabolic phenotypes, on the outcomes of tea-based interventions. This synthesis thus advances a novel “component-microbiota-metabolite-host” axis as a unifying framework for understanding tea’s pleiotropic mechanisms in gastrointestinal health. Beyond mechanistic insight, the review lays a conceptual foundation and proposes a translational roadmap for developing evidence‑based, personalized tea interventions aligned with precision nutrition.
Yue R, Wen Y, Zhao S, Liu X, Luo L, Liu Y, Zeng L
High thrombin activity associated with crohn’s disease induces microbiota pathogenicity contributing to mucosal inflammation.★ Gut microbes | 2026-06-17
Thrombin is a serine protease produced by the intestinal epithelium that contributes to mucosal homeostasis by limiting microbial encroachment. In Crohn’s disease, mucosal thrombin activity is markedly increased, suggesting a role in disease pathophysiology. We hypothesized that excessive luminal thrombin disrupts host-microbiota interactions and promotes a pathogenic microbial phenotype. Thrombin levels were significantly elevated in fecal samples from a subset of Crohn’s disease patients compared with healthy controls. Ex vivo experiments using human colonic biopsy-derived microbiota, cultured as polymicrobial biofilms, revealed that thrombin exposure disrupted biofilm integrity, enriched the protein-rich extracellular matrix, and promoted bacterial dispersal. Dispersed bacteria displayed enhanced adhesion to intestinal epithelial cells and triggered inflammatory and antimicrobial responses through Toll-Like Receptor 5 signaling. Although the global taxonomic composition showed limited changes, metatranscriptomic analyses demonstrated distinct microbial activity profiles in the presence of thrombin. In vivo, intracolonic thrombin altered mucosal biofilm organization in mice, and the transfer of thrombin-exposed mucosal microbiota to germ-free recipients induced mucosal inflammation and bacterial translocation. Finally, in a rat model of colitis, pharmacological inhibition of thrombin activity restored mucosal biofilm architecture and reduced tissue damage. These findings identify thrombin as a host-associated modulator of microbial functional dysbiosis in patients with Crohn’s disease. By driving a shift toward a pathogenic microbial phenotype, excessive thrombin links epithelial activity with altered host-microbiota interactions and mucosal inflammation. Thrombin measurement in fecal samples may represent a non-invasive marker of microbiota pathogenicity, and therapeutic targeting of thrombin offers a promising complementary strategy to immune-directed treatments in Crohn’s disease.
Le Cosquer G, Pannier M, Thevenin J, Guiraud L, David M, Dumas A, Meunier E, Rousset P, Palese S, Giorgio C
Structural characterization and the protective effects of green walnut husk polysaccharides by modulating inflammation and gut microbiota for inflammatory bowel disease.★ International journal of biological macromolecules | 2026-06-17
An acidic polysaccharide, designated GWHP, was isolated from the husk of Juglans regia L. (green walnut husk). Its protective activity and anti-inflammatory mechanisms were systematically investigated using lipopolysaccharide (LPS)-induced MODE-K cell model and dextran sulfate sodium (DSS)-induced colitis in mice. Structural characterization revealed that GWHP consisted of galacturonic acid (76.2%), galactose (8.5%), arabinose (7.4%), rhamnose (6.5%), and fucose (1.4%), with an average molecular weight of 108 kDa. GWHP administration significantly enhanced the activities of antioxidant enzymes including GSH-Px, SOD, CAT, while reduced the malondialdehyde accumulation. In LPS-induced MODE-K cells, GWHP efficiently downregulated the secretion of pro-inflammatory cytokines (IL-1β, TNF-α, and IL-6) and promoted the release of the anti-inflammatory cytokine IL-10. In the DSS colitis model, GWHP administration effectively improved colonic physiological indices. Histopathological analysis further verified its dose-dependent efficacy in repairing colonic tissue damage. Furthermore, GWHP rebalanced systemic inflammatory responses by significantly reducing serum pro-inflammatory cytokines levels (TNF-α, IL-1β and IL-6) and upregulating the expression of anti-inflammatory IL-10. In addition, GWHP also rescued gut microbial diversity and community structure, specifically enriching the relative abundance of Lactobacillaceae and inhibiting the growth of opportunistic pathogens in Enterobacteriaceae. Network pharmacology analysis further verified stable binding affinity between GWHP and dopamine receptor D2, providing clues to its underlying molecular mechanism. In conclusion, GWHP can efficiently alleviate intestinal inflammatory injury, maintain gut microbiota homeostasis, and restore intestinal barrier function. These findings suggest that GWHP holds great potential as a natural functional food ingredient or preventive agent for the intervention of inflammatory bowel disease.
Li N, Geng J, Xu Y, Li SY, Li M, Zhang H, Dong L
Fecal and colonic microbiota differ in composition, function, diagnostic utility and correlation with inflammatory cytokines in ulcerative colitis. Scientific reports | 2026-06-16
Fecal samples have been frequently used to investigate ulcerative colitis (UC)-related gut microbiota study due to their easy availability. However, whether fecal microbiota accurately represents the mucosal microbiome of UC patients remains controversial. This study aims to analyze the gut microbiota in feces and colonic tissue, and to demonstrate from different perspectives whether the gut microbiota in feces can fully characterize the gut microbiota in colonic tissue. We employed 16S rRNA sequencing and standardized microbiome analysis for fecal and colon tissue samples from 12 UC patients and 16 non-IBD controls (NIC). And we also integrates ELISA, functional analysis, and machine learning techniques to discuss the similarities and differences among differentially identified UC-related microorganisms screened from two sample types. As results, colonic tissue exhibited greater microbial diversity than feces. And some taxa were only detected in colonic tissue. In UC, α-diversity was higher in colonic tissue but lower in feces compared to NIC. Only two microbial genera (Ligilactobacillus and Intestinimonas) showed consistent differential abundance across both sample types. At the functional pathway level, both fecal and colonic microbiota were primarily associated with metabolic pathways; however, colonic microbiota were additionally linked to immune-related pathways, such as the NOD-like receptor signaling pathway. IL-1β, IL-17 and IL-22 were significantly overexpressed in UC. Most fecal differential microbes were negatively correlated with those three cytokines. Regarding the two shared differentially expressed genera, abundance of Ligilactobacillus in tissues was more strongly correlated with the expression of inflammatory cytokines. The correlation between the abundance of Intestinimonas and the expression levels of inflammatory cytokines showed opposite trends in tissues and feces. The combined SHAP and random forest algorithms shown that the UC classification model based on tissue markers was more stable and exhibited weaker overfitting than the model based on fecal markers. In general, fecal microbiota profiles did not adequately represent the microbial landscape of colonic tissue in patients with UC. For studies investigating disease mechanisms, colonic tissue was the more appropriate sample type. However, due to its accessibility, fecal samples remained a promising source for microbial biomarker discovery and the development of diagnostic models.
Chen W, Zhao Q, Li J, Ainiwaer Z, Zhang C, Palihati A, Fu W, Wu H, Huang X
Power and sample-size estimation in human microbiome research.Review★ Med (New York, N.Y.) | 2026-06-16
Human microbiome research has become pivotal in advancing our understanding of complex diseases such as diabetes, inflammatory bowel disease, and cancer. Much of this work relies on comparing microbial communities across health and disease states, or case-control cohorts, using high-throughput metagenomic sequencing. Yet the very nature of sequencing-derived microbiome data makes robust cohort design and power-based sample-size estimation unusually difficult. Unlike other omics, microbiome profiles are compositional, sparse, and often zero inflated, properties that complicate statistical modeling and inflate sample-size requirements. These challenges are further compounded by the diversity of analytical frameworks-ranging from diversity indices to causal inference-each built on different statistical assumptions and optimized for a distinct research hypothesis. This review synthesizes current approaches around the study design and sample-size estimation in microbiome research, aiming to provide clinicians and researchers with practical guidance for navigating the statistical complexities unique to this field.
Zhou Q, Lu Y, Wang L, Zhou W, Oba H, Zhou Y, Shen M, Qu X, De Souza C, Rayner A
Fungal abundance across flare and remission in ulcerative colitis patients. Gut pathogens | 2026-06-16
Ulcerative colitis (UC) is associated with gut microbiota alterations, but the role of the fungal microbiota remains underexplored. We conducted a prospective study quantifying absolute bacterial and fungal abundance in faecal samples from UC patients with varying disease activity. We amplified the ITS2 sequence (fungi) and 16 S rRNA gene (bacteria) in three groups of patients: UC long remission (UClr); UC short remission (UCsr) and UC flare (UCfl). Two faecal samples from UClr and UCsr, and one sample from UCfl group (at flare-onset) were collected. Eighty-seven patients were included: 29 UClr, 20 UCsr, and 38 UCfl. Across all patients, fungal ITS2 gene copies were markedly lower than bacterial 16 S rRNA copies (median 9.27E + 05 vs. 4.28E + 11 copies/g), with a fungal-to-bacterial ratio of 1:461,000. Fungal abundance was significantly higher in UCfl than in UClr (p = 0.0026), but not UCsr. The ITS2/16S ratio was also elevated in UCfl versus both remission groups (p < 0.01). Over time, fungal abundance showed greater variability than bacterial abundance, with a modest but significant decrease in the ITS2/16S ratio at 8 weeks (p = 0.029). While bacterial loads remained stable across disease states, fungal abundance and the fungal-to-bacterial ratio were higher during UC flares. These findings describe an association between fungal dynamics and disease activity in UC and support further investigation of inter-kingdom microbial relationships in this context.
Herrera-deGuise C, Varela E, Sarrabayrouse G, Yáñez F, Mayorga-Ayala L, Robles-Alonso V, Céspedes-Martínez E, Serra-Ruiz X, Lastiri E, Guarner F
The Regulatory Mechanisms of Indole-3-Carboxaldehyde in Immune Cells and Its Role in Autoimmune Diseases.Review Pharmacological research | 2026-06-16
Immune cells play a central role in the pathogenesis and progression of autoimmune diseases. Recent evidence indicates that metabolites produced by the gut microbiota are essential for maintaining immune cell homeostasis. Indole-3-carboxaldehyde (IAld), a key gut microbial metabolite, has garnered considerable attention due to its immunomodulatory properties in autoimmune diseases. In multiple sclerosis, IAld alleviates inflammation through modulation of mast cells and astrocytes; in rheumatoid arthritis (RA), IAld suppresses macrophage-mediated inflammation while concurrently promoting angiogenesis and osteoclastogenesis; in inflammatory bowel disease (IBD), IAld confers protection through reducing inflammatory responses, promoting intestinal barrier repair, and modulating the gut microbiota composition. IAld mediates its immunomodulatory effects by directly or indirectly modulating immune cell function, including secretion and regulatory activity (including neutrophils, macrophages, innate lymphoid cells, T cells, and others) via the aryl hydrocarbon receptor (AhR) signaling pathway. In this review, we summarize the mechanisms by which IAld acts on immune cells and discuss its implications for autoimmune disease pathogenesis. Finally, we outline current challenges in this field and provide a perspective on future research priorities.
Xin Y, Cen Q, He J, Lu W, Yu Y, Jing F, Zhao Y, Jin J, Cui Y, Feng J
Harnessing edible extracellular vesicles for inflammatory bowel disease: From natural immunomodulators to bioengineered oral nanotherapeutics.Review Pharmacological research | 2026-06-16
Inflammatory bowel disease (IBD) is a chronic, relapsing disorder of the gastrointestinal (GI) tract driven by complex interactions among mucosal immune dysregulation, epithelial barrier degradation, and microbial dysbiosis. Current therapies achieve only partial disease control and are limited by systemic toxicity, suboptimal response rates, and an inability to simultaneously restore epithelial integrity and microbial homeostasis. Colon-targeted oral delivery offers direct mucosal access with reduced systemic exposure; however, conventional oral formulations remain constrained by GI barriers, including proteolytic degradation, bile salt emulsification, and mucus entrapment, highlighting the need for more biocompatible delivery platforms. Edible extracellular vesicles (EEVs), encompassing plant- and milk-derived vesicles, have emerged as biogenic vehicles with the potential to partially withstand these delivery barriers. Their relative structural stability and cross-kingdom regulatory cargoes may allow EEVs to better traverse the oral-gut axis. Mechanistic studies reveal that these vesicles reprogram the intestinal inflammatory milieu by modulating immune networks, fortifying the epithelial barrier, and restoring microbiota homeostasis. Furthermore, their biodistribution enables therapeutic targeting beyond the colon, mitigating extraintestinal manifestations. In this review, we summarize the biophysical properties and immunomodulatory mechanisms of natural EEVs. We also discuss the translational limitations of native EEVs, including batch variability and payload leakage, and highlight the bioengineering strategies developed to address these challenges. Finally, we explore how integrating stimuli-responsive architectures from synthetic nanomedicine with EEVs’ GI resilience may inform the design of next-generation oral platforms for IBD management.
Yang C, Chen J, Xu Y, Xu J, Chen N
Cucurbitacin derivatives (B, IIa, IIb, and E): modulating gut dysbiosis and inflammatory pathways for multi-target therapy of ulcerative colitis.Review Inflammopharmacology | 2026-06-15
Ulcerative colitis (UC) is a colon-associated inflammatory bowel disease (IBD) that extends from rectum to complete colon characterized by ulceration, rectal bleeding, bloody diarrhoea, and abdominal pain, epithelial barrier disruption, gut dysbiosis, immune dysregulation and recurrent mucosal inflammation. Today, several clinical medications such as corticosteroids, aminoslicylates and immuno-modulators are available, but each one of them have their own side effects. Therefore, to overcome these limitations, we are moving toward herbal drug therapies. This review presents the emerging role of Cucurbitacin (Cu), a highly oxygenated tetracyclic triterpenoid compound found in a variety of Cucurbitaceae plants and known for its anti-inflammatory response. Unlike previous reviews which just focuses on single derivatives or isolated mechanisms, this review focuses on multi-target analysis of Cucurbitacin (Cu) derivatives- CuB, CuE, CuIIa, and CuIIb, their biosynthesis, structure-activity relationships (SAR), inflammatory pathway modulation, gut microbiota regulation, extracellular vesicle-associated microRNAs, and differentially expressed genes (DEGs). The preclinical evidences shows that these derivatives of Cu have capability to treat UC, by inhibiting the Inflammatory pathways such as NLRP3 inflammasome, NF-κB, JAK2/STAT3, MAPK and EGFR, which results in decreasing the level of Inflammatory cytokines such as IL-6, IL-1β and TNF-α. They also upregulates the SCFAs producing beneficial bacteria and downregulates the harmful bacteria, thereby restoring epithelial integrity. Notably, Cu Ⅱa is associated with alteration in composition of protein and microRNA in extracellular vesicles. All these factors help in the treatment of UC. Although preclinical findings are encouraging, the current evidence is largely restricted to DSS induced animal models and the clinical validation in human is still lacking. Various challenges related to narrow therapeutic windows, poor bioavailability, and toxicity require resolution before clinical translation. This review find these translational gaps and proposes targeted research directions including nanoformulation strategies, pharmacokinetic profiling, and early-phase clinical evaluation.
Devi R, Dadwal P, Sharma N, Singh A, Arora A
Efficacy and Safety of Probiotics, Prebiotics, and Synbiotics: An Umbrella Review of Systematic Reviews and Meta-Analysis of Randomized Controlled Trials. Nutrition reviews | 2026-06-15
Biotics, which include probiotics, prebiotics, and synbiotics, are widely used for health promotion and disease management, but evidence on their efficacy and safety across populations remains fragmented. To synthesize recent evidence on efficacy and safety of prebiotics, probiotics, and synbiotics to inform clinical application and future research. Literature searches were performed in the PubMed, Embase, and Web of Science databases focusing on biotic interventions and their clinical outcomes across different populations and clinical conditions. Eligible studies were systematic reviews and meta-analyses of randomized controlled trials published since 2023, because more recent reviews incorporate updated trial evidence and reduce duplication of earlier findings. Data extracted included general study characteristics, all effect estimates generated by the pairwise meta-analyses, and statistically significant comparison estimates derived from the network meta-analyses. Data from 128 systematic reviews and meta-analyses were synthesized. Findings showed that certain probiotics reduce necrotizing enterocolitis in infants and improve glycemic control, lipid profiles, and inflammation in patients with type 2 diabetes mellitus. Benefits were also observed in gastrointestinal disorders (ie, irritable bowel syndrome, inflammatory bowel disease, and constipation), gynecological conditions, and some neurological and psychiatric disorders. However, effects varied by strain, population, and condition. Most biotics were well tolerated; however, safety concerns, such as increased risk of sepsis in vulnerable pediatric populations, were noted. Substantial heterogeneity across studies, particularly in network meta-analyses, limited comparability. Biotics offer promising but selective clinical benefits depending on the condition and population. Although generally safe, their application should be condition specific. Standardization in future trials is essential to improve comparability and guide evidence-based recommendations for the clinical use of biotics. PROSPERO registration No. CRD420251010116.
Hoang T, Kim J
Unravelling the Critical Interplay of Oral and Gut Microbiota in Disease Development. Current medicinal chemistry | 2026-06-15
The oral microbiota, comprising bacteria, fungi, and viruses, plays a critical role in initiating food digestion, serving as the first defense against pathogenic invasion and maintaining oral homeostasis. In contrast, the gut microbiota, consisting of trillions of microorganisms, functions as a barrier protection, modulating the immune system and facilitating the absorption of nutrients. Although they have distinct anatomical locations, these ecosystems are highly interconnected and play a pivotal role in human health and disease. The most common routes of interaction between the oral and gut microbiota are the enteral, the hematogenous, and the immune cell migration routes. Many oral pathogens interact with intestinal microbes, activating the host’s mechanisms that establish dysbiosis and pave the way for the development of various diseases, ranging from inflammatory bowel disease and colorectal cancer to metabolic and neurodegenerative disorders. In this review, we delineate the mechanisms underlying these ecosystems to offer novel insights into disease pathogenesis while also unveiling new avenues for preventive and therapeutic interventions. Although current therapeutic approaches include the administration of antibiotics, prebiotics, and probiotics, novel personalized therapeutic approaches have also emerged. Fecal microbiota transplantation (FMT), gut bacteria engineering, nanomedicine-based techniques, and the use of miRNA to foster microbiota balance in both compartments hold great promise and may prove critical for the prevention and management of systemic diseases.
Pouliou C, Poulios P, Piperi C
DOI: 10.2174/0109298673440488260516210738 | View on PubMed →
Lonicera japonica polysaccharide restores mucosal integrity in ulcerative colitis by increasing microbiota-derived spermidine.★ Cell reports | 2026-06-15
WLJP-025p, a homogeneous polysaccharide from Lonicera japonica Thunb., alleviates experimental ulcerative colitis in mice by reshaping the gut microbiota and restoring intestinal spermidine. Microbial fermentation, microbiota depletion, and microbiota transplantation support a microbiota-dependent mechanism. Microbiota-derived spermidine interacts with HADHA and partially reverses inflammatory HADHA-associated metabolic reprogramming, as shown by restored fatty acid oxidation (FAO), reduced lactate accumulation, improved basal respiration and etomoxir-sensitive oxygen consumption rate (OCR), and preserved epithelial integrity in Caco-2 cells and intestinal organoids. In vivo, WLJP-025p dose-dependently reduces colitis pathology and inflammation, partially reverses FAO-related metabolic disruption, and promotes epithelial maturation and barrier integrity. Serum biochemical and protein analyses further support reduced systemic inflammation and improved mucosal homeostasis. These findings define a microbiota-derived spermidine-HADHA axis that supports mucosal homeostasis in ulcerative colitis.
Bai X, Rao X, Tian K, Wang C, Shen H, Li H, Liu P
DsbA-L safeguards T cell mitochondrial redox homeostasis to restrain Th17 differentiation and colitis. Cell death & disease | 2026-06-13
Pathogenic Th17 accumulation drives intestinal inflammation in inflammatory bowel disease (IBD), yet the metabolic mechanisms directing Th17 polarization remain incompletely understood. Here, we identify the mitochondrial matrix protein DsbA-L serves as a critical, cell-intrinsic metabolic checkpoint for Th17 differentiation and intestinal immune homeostasis. In mouse models, dextran sulfate sodium (DSS)-induced colitis downregulated DsbA-L expression and disrupted mitochondrial redox balance in intestinal CD4⁺ T cells. T cell-specific DsbA-L deletion exacerbated colitis and selectively promotes pathogenic Th17 differentiation by increasing mitochondrial reactive oxygen species (mtROS). Pharmacological mtROS scavenging reverses the Th17 bias, establishing mitochondrial redox imbalance as a causal driver of pathogenic polarization. Furthermore, DsbA-L is essential for the therapeutic efficacy of the PPARγ agonist rosiglitazone in colitis. Collectively, our findings position DsbA-L-mediated mitochondrial redox balance as a key regulator of Th17 pathogenicity and intestinal inflammation, offering new conceptual and therapeutic insights for precision intervention in IBD.
Deng J, Wang L, Liu B, Wang J, Li Q, Deng Y, Yan L, Luo H, Meng W, Liu F
Interleukin-8-Driven Monocyte Activation in Primary Sclerosing Cholangitis: Insights from Single-Cell Analysis and Humanized Immune System Mice. JHEP reports : innovation in hepatology | 2026-06-12
Primary sclerosing cholangitis (PSC) is an immune-mediated liver disease with an incompletely understood pathogenesis. Monocyte/macrophage cell dysregulation has been suggested to contribute, although their functional relevance remains insufficiently understood. The main aim of this study was to identify peripheral myeloid cell populations involved in PSC pathogenesis and assess the therapeutic potential of targeting associated inflammatory signalling pathways. Additionally, we sought to enhance translational relevance through the application of a humanized immune system (HIS) mouse model. Peripheral blood mononuclear cells from PSC and ulcerative colitis patients and from healthy controls were profiled using cellular indexing of transcriptomes and epitopes by sequencing. Inflammatory signalling via the IL-8:CXCR1/2 axis was further evaluated in both conventional and HIS mouse models of cholestatic liver disease. Our data show that PSC patients exhibit a population of circulatory CXCL8+CD14+ monocytes with upregulated proinflammatory signalling. Serum concentrations of the proinflammatory cytokine IL-8, encoded by CXCL8, were increased in PSC patients (p<0.001) and associated with poor prognosis. PSC patients with high IL-8 concentrations (≥ 27.8 pg/mL) at baseline had a significantly worse transplant-free survival in comparison to patients with low IL-8 concentrations (logrank hazard ratio 6.12, 95% CI 1.68-22.33). Intrahepatic IL-8+ macrophages were expanded during disease progression (p<0.05). Pharmacologic Cxcr1 antagonism in conventional rodent immune system and antibody-mediated IL-8 neutralization in HIS mice reduced cholestatic liver injury. A circulatory CXCL8+CD14+ monocyte subset and intrahepatic IL-8+ macrophages were identified as potential contributors to PSC pathogenesis. HIS mouse models could mark a significant advance in translational research on human immune responses. Targeting the IL-8:CXCR1/2 axis may represent a promising therapeutic strategy and urges further investigation.
Heyerick L, De Vos Z, Baekelandt A, De Muynck K, Matthys R, Morren L, Gökce E, Meese T, Van Der Linden M, Hoorens A
Paeoniflorin as a Promising Therapeutic Candidate in Intestinal Diseases: Experimental Evidence, Mechanistic Insights, and Translational Perspectives.Review Drug design, development and therapy | 2026-06-09
Intestinal diseases, including inflammatory bowel disease, functional bowel disorders, stress-related enteropathy, colorectal cancer, and colitis-associated colorectal cancer, share overlapping pathological processes such as epithelial barrier disruption, immune dysregulation, microbiota imbalance, oxidative stress, and inflammation-driven tissue injury. Paeoniflorin, a major monoterpene glycoside derived from Paeonia species, has attracted increasing attention because of its anti-inflammatory, antioxidant, immunomodulatory, anti-apoptotic, and barrier-protective properties. This review summarizes experimental evidence and mechanistic findings regarding the therapeutic potential of paeoniflorin in intestinal diseases. Current preclinical studies suggest that paeoniflorin can alleviate colitis, improve epithelial barrier integrity, promote mucosal repair, modulate microbiota-metabolite interactions, reduce visceral hypersensitivity, and suppress inflammation-associated colorectal tumorigenesis. Mechanistically, these effects involve coordinated regulation of inflammatory signaling, immune-cell balance, epithelial regeneration, gut-brain axis-related pathways, and oncogenic inflammatory cascades. Recent advances in colon-targeted delivery, pharmacokinetic modulation, compatibility-dependent exposure, and derivative development further support its translational potential. However, existing evidence remains largely based on in vitro and animal studies, with limited clinical data, heterogeneous models and dosing regimens, insufficient PK/PD validation, and unresolved druggability challenges. Future research should integrate mechanistic validation, optimized delivery systems, exposure-response evaluation, and clinically relevant disease stratification to support its progression from a bioactive natural compound to a viable intestinal therapeutic candidate.
Chang C, Xue J, Xu Z, Hou G
Histologic signatures as predictors of intestinal barrier impairment in inflammatory bowel disease: integration with endoscopic and molecular markers.★ Journal of Crohn’s & colitis | 2026-06
Intestinal barrier impairment (BI) is a hallmark of inflammatory bowel disease (IBD), driving immune activation, neutrophil-mediated injury, and chronic mucosal damage. While endoscopy and molecular profiling provide insight into epithelial and vascular assessment, the combined prognostic role of histology and BI remains insufficiently defined. This study aimed to determine the association between histology-derived signatures and BI, and identify outcome predictors by integrating histologic, advanced imaging, and molecular data. IBD patients underwent in vivo epithelial and vascular barrier assessment using probe-based confocal laser endomicroscopy and endocytoscopy. Biopsies were collected for histologic and protein expression analysis. Epithelial (ZO-1, Claudin-2, E-cadherin) and vascular-barrier proteins (CD31, PV-1) were analyzed using confocal microscopy and automated quantification with QuPath. Correlation among histology, advanced imaging, and protein expression was assessed, together with the ability to predict outcome at 12 months of follow-up. Eighty-eight IBD patients (52 Crohn’s disease [CD] and 36 ulcerative colitis [UC]) were included. BI was identified in 35/52 (67%) CD and 28/36 (78%) UC patients. Epithelial and lamina propria neutrophils correlated strongly with epithelial BI (r = 0.6). Chronic inflammatory infiltrate correlated significantly with vascular BI (r = 0.5) and PV-1 expression (r = 0.3) in CD. Finally, CD patients with both barrier alterations (advanced imaging + PV-1) and inflammatory infiltrate showed a higher rate of adverse outcomes than those with single alterations. Histologic signatures correlate significantly with BI in IBD. Multimodal evaluation combining histology, advanced imaging, and molecular profiling improves outcome prediction beyond single-modality assessment and may identify patients with subclinical disease persistence, supporting accurate risk stratification and personalized management.
Lo Bello A, Zammarchi I, Pugliano CL, Majumder S, Hughes R, Crotty R, Hayes B, Burke L, Ghosh S, Iacucci M
Mesenteric Adipose Tissue as a Modulator of Intestinal Inflammation: Mechanistic Insights and Model Systems in Crohn’s Disease.Review European journal of immunology | 2026-06
Inflammatory bowel disease, including Crohn’s disease (CD) and ulcerative colitis, is becoming increasingly prevalent. Obesity, specifically visceral adiposity, has been identified as a significant risk factor for disease recurrence and complications. A hallmark of CD is the development of “creeping fat”, which is characterized by adipocyte hyperplasia and increased adipokine secretion. Under homeostatic conditions, adipose tissue plays a key role in immune regulation through the secretion of adipokines, such as leptin and adiponectin, which modulate JAK/STAT, AMPK, and NF-kB pathways in immune and epithelial cells. However, in obesity and under metabolic stress, mesenteric adipose tissue undergoes immune remodelling marked by macrophage polarization, Th1/Th17 differentiation, and fibroblast reprogramming driven by TNFα, IL-6, and TGF-β1. These changes promote sustained cytokine production, extracellular matrix deposition, and fibrostenotic remodelling of the intestinal wall. This review highlights current evidence linking mesenteric adipose tissue and creeping fat immunometabolism to intestinal inflammation in CD. We outline key cellular and signalling mechanisms that connect mesenteric adipose to mucosal immune dysregulation and discuss emerging experimental models.
Omar T, Weidinger C, Siegmund B
Surgery & Complications (15 papers)
Sexual Distress Is Common in Long Term Follow-up After Pelvic Pouch for Ulcerative Colitis: A Cross-Sectional Study. Diseases of the colon and rectum | 2026-06-19
Sexual dysfunction is common following pelvic pouch surgery for ulcerative colitis. Despite this, little work has been done to explore the degree of sexual distress this causes in patients. To determine the proportion of patients with ulcerative colitis who experience sexual distress following pelvic pouch surgery and to explore the effects of social demographics, age, bowel function, anxiety, and depression on sexual distress. A cross-sectional survey that was emailed to patients. A large tertiary care teaching hospital. Patients who underwent pelvic pouch surgery for ulcerative colitis from 1980-2022. Validated questionnaires included the 13-item Sexual Distress Scale, Hospital Anxiety and Depression Scale, and Colorectal Functional Outcome questionnaire. The primary outcome was the proportion of patients meeting established thresholds for sexual distress. Multivariable regression was used to evaluate associations between sexual distress and operative factors, age, sex, income, education, ethnicity, sexual orientation, and relationship status. Of 1830 eligible patients, 497 responded and were included in the analysis. Overall, 194 patients (39%) screened positive for sexual distress. Women were disproportionately affected, with more than half reporting clinically significant distress (141/243, 57.8%). Female gender was the only independent preoperative predictor of sexual distress on multivariable analysis (odds ratio = 4.796, 95% CI: 3.119, 7.374, p < 0.001). Poor bowel function, anxiety, and depression were all significantly more prevalent among patients with sexual distress (all p < 0.001). Cross-sectional design limits causal inference. Selection and response bias are possible. Sexual distress is common following pelvic pouch surgery for ulcerative colitis, particularly among women, and is strongly associated with bowel dysfunction, anxiety, and depression. These findings highlight the importance of holistic pre- and postoperative counselling and consideration of psychological screening in follow-up care. Further research is needed to elucidate underlying mechanisms and develop targeted interventions. See Video.
Johnson G, Hart TL, Brar MS, Schmocker S, Pooni A, Vernon J, Kennedy E
Adjunctive GLP1 Receptor Agonists in Patients with Inflammatory Bowel Diseases and Obesity and/or Diabetes: A Target Trial Emulation.★ Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association | 2026-06-17
We conducted a target trial emulation study to examine the effect of two glucagon-like peptide-1 receptor agonists (GLP1RAs) (semaglutide and tirzepatide) on clinical outcomes in patients with inflammatory bowel diseases (IBD) with obesity and/or diabetes. We emulated a target trial of GLP1RAs in eligible, stable patients with IBD (no steroid use, no IBD-related hospitalization or surgery and stable dose of IBD therapy for >6 months) with comorbid obesity and/or diabetes using observational data from an administrative claims database (OptumLabs Data Warehouse) between 2018-23. We created two separate cohorts: (cohort 1) background 5-ASA or no IBD-directed medications; (cohort 2) background advanced therapies and/or immunomodulators. We compared 1-year risk of relapse (composite of IBD-related hospitalization, surgery or prednisone use) and safety with GLP1RA initiation vs. non-initiation, after 1:1 propensity score matching. (Cohort 1) In 2028 patients initiated on GLP1RAs (63±11y, 63% female, 71% with UC) matched 1:1 to GLP1RA non-initiators, there was no difference in risk of relapse (7.9% vs. 7.9%; RR,1.01 [95% CI,0.82-1.24]) or safety outcomes (7.0% vs. 7.9%; RR,0.88 [0.71-1.10]); 36% patients discontinued GLP1RAs within 1 year. (Cohort 2) In 346 patients initiated on GLP1RAs (59±12y, 62% female, 43% with UC) matched 1:1 to GLP1RA non-initiators, no significant difference was observed in the risk of relapse (12.4% vs. 15.6%; RR,0.80 [0.55-1.15]) or safety outcomes (5.5% vs. 6.6%; RR,0.88 [0.48-1.58]); 33% patients discontinued GLP1RAs within 1 year. Adjunctive treatment with semaglutide or tirzepatide does not improve outcomes in patients with stable IBD on advanced therapies and/or IMM and/or 5-ASA.
Yeh KH, Ahuja D, Patel SB, Xu R, Park SK, Gold S, Ramos GP, Malik T, Kaur M, Bering J
Neurofeedback as a non-pharmacological strategy for pain and gut-brain axis disorders: clinical relevance in inflammatory bowel disease. Minerva gastroenterology | 2026-06-17
Inflammatory bowel diseases (IBD), including Crohn’s disease and ulcerative colitis, are chronic conditions associated with gastrointestinal inflammation and a wide range of extraintestinal manifestations. While conventional treatments primarily address intestinal inflammation, many patients continue to experience chronic pain, psychological comorbidities, and functional gastrointestinal symptoms, highlighting the need for integrated therapeutic strategies. This narrative review explores the potential of neurofeedback (NFB) as a non-invasive therapeutic approach for managing symptoms frequently observed in IBD, including musculoskeletal pain, anxiety, depression, post-traumatic stress symptoms (PTSS), and gut-brain axis dysfunction. In the absence of direct evidence on neurofeedback in IBD populations, we examined data from clinical trials conducted in conditions that are frequently comorbid with or symptomatically overlap with inflammatory bowel disease, including fibromyalgia, irritable bowel syndrome (IBS), chronic pain syndromes, and affective or trauma-related disorders. We focused on outcomes related to chronic pain, psychological well-being, and gastrointestinal function, examining NFB protocols primarily targeting alpha, theta, and sensorimotor rhythms, which have shown promising results in improving symptom severity and autonomic regulation. These findings support the rationale for investigating NFB as a potential adjunctive therapy in IBD, particularly for patients with residual or refractory extraintestinal symptoms. However, as none of the available studies specifically involve patients with IBD, the evidence base remains indirect. Moreover, current findings are limited by small sample sizes, heterogeneous methodologies, and variable outcome measures in the studied populations, making it difficult to draw definitive conclusions regarding the efficacy of NFB in this context. Future research should include large-scale, randomized controlled trials conducted directly in IBD cohorts, along with protocol standardization and individualized approaches based on neurophysiological profiles. Clarifying the therapeutic potential of NFB in this population could open new avenues for non-pharmacological, patient-tailored interventions within integrative care frameworks.
Spagnolo G, Ferrarese D, DI Vincenzo F, Iaccarino J, Murgiano M, Vecchione M, Puca P, D’Onofrio AM, Natalello G, D’Agostino MA
End-to-Side Ileocolonic Anastomosis after Ileocecectomy for Crohn’s Disease is a Safe Option with Low Recurrence. Diseases of the colon and rectum | 2026-06-17
The recent advent of the Kono-S anastomosis has raised the question of the impact of anastomotic configuration on recurrence following ileocecectomy for Crohn’s disease. Determining if there is a superior configuration is an opportunity for improvement in optimization in surgical care for Crohn’s disease patients. At the University of Chicago, we perform a variety of anastomotic configurations, including side-to-side, end-to-end, end-to-side, side-to-end and Kono-S. Determine if there is a difference in recurrence between anastomotic configurations following ileocecectomy for Crohn’s disease at a high volume IBD center. Retrospective chart review. The University of Chicago Medical Center. Two hundred thirty-nine patients who underwent ileocecectomy for Crohn’s disease from January 1, 2018, through December 31, 2022. Endoscopic recurrence rate for each anastomotic configuration. 239 patients with Crohn’s disease who underwent ileocecectomy were included. The anastomotic configurations were similar in terms of patient characteristics. The end-to-side anastomoses were associated with lower blood loss and shorter OR times. On multivariable analysis, elective surgery and end-to-side anastomotic configuration were associated with lower recurrence of Crohn’s disease at an average follow-up of 32 months. Study is retrospective in nature and conducted at a single institution. End-to-side anastomosis configuration is a safe, technically easy to perform reconstruction method that may reduce the rate of disease recurrence. See Video Abstract.
Kinford CW, Tijerina M, Nordgren RK, Rubin DT, Hurst RD, Shogan BD, Shaffer VO, Olortegui KS
Segmental versus extended colectomy for colonic Crohn’s disease in advanced therapy era: a systematic review and Bayesian meta-analysis.Review Techniques in coloproctology | 2026-06-16
The optimal extent of resection for colonic Crohn’s disease (CD) remains controversial. Segmental colectomy (SC) may preserve bowel and avoid permanent stoma but has been historically associated with higher recurrence than extended colectomy (EC). In the advanced therapy era, contemporary data and Bayesian methods may refine this risk-benefit balance. PubMed, Embase, and Cochrane Library were searched from inception to December 1, 2025. The primary outcome was surgical recurrence; secondary outcomes were reoperation, permanent stoma, overall postoperative complications, and mortality. Frequentist random-effects models (restricted maximum likelihood) were used to pool odds ratios (ORs) with 95% confidence intervals (CIs), with heterogeneity assessed by I2 and leave-one-out analyses. Bayesian random-effects meta-analyses (bayesmeta) were performed for surgical recurrence, reoperation, and permanent stoma using vague priors and empiric Turner priors for heterogeneity, with additional models incorporating historical evidence from the advanced therapy era. Five observational studies (1095 patients; 501 SC, 594 EC) were included. Surgical recurrence did not differ significantly between SC and EC (OR 1.15; 95% CI 0.53-2.50; I2 = 74%). Reoperation (OR 1.36; 95% CI 0.71-2.61; I2 = 68%), permanent stoma (OR 0.22; 95% CI 0.03-1.39; I2 = 87%), and overall complications (OR 0.75; 95% CI 0.40-1.40; I2 = 64%) were also not significantly different. Mortality was reported in one study (1 SC vs 5 EC). Bayesian models suggested a higher probability of surgical recurrence and reoperation after SC but with wide credible intervals and substantial heterogeneity, whereas SC showed a consistently high probability of reducing permanent stoma risk (posterior OR ~ 0.23; P[OR ≤ 1] > 0.95 in primary models; reinforced by historical priors). Leave-one-out analyses identified influential studies for some outcomes but did not materially alter the overall interpretation. All studies had a moderate risk of bias, mainly due to confounding and selection. In contemporary observational evidence, SC and EC show broadly comparable outcomes for surgical recurrence, reoperation, complications, and mortality, while SC is strongly favored with respect to permanent stoma avoidance. Operative decision-making should weigh a probable increase in recurrence risk after SC against the clinically meaningful functional benefit of stoma preservation, recognizing the limitations imposed by observational designs, heterogeneity, and sparse data.
Delgado LM, Pompeu BF, Peñaranda LM, Martins GHA, Viana P, Theis C, de Figueiredo SMP, Formiga FB
Inflammatory bowel disease outcomes among hospitalized homeless individuals. BMC gastroenterology | 2026-06-16
There is a paucity of outcome data among homeless individuals with inflammatory bowel diseases (IBD). We reported rates of homelessness among inpatients with Crohn’s disease (CD) and ulcerative colitis (UC) and examined inpatient outcomes. The Healthcare Utilization Project (HCUP) State Inpatient Databases from New York, Arizona, Massachusetts and Florida for 2013 and 2014 were used to identify adults ≥ 18 years admitted with IBD identified by ICD-9 codes. Homeless patients were propensity score matched using a one-to-ten greedy nearest-neighbor approach to non-homeless patients to balance the distribution of baseline covariates. Differences in mortality, endoscopy utilization, surgical treatment and post-operative complications were reported as odds ratios with 95% confidence intervals (CI). A total of 115,008 IBD hospitalizations were identified of which 61% (n = 70,457) were CD discharges while 39% (n = 44,551) were UC discharges. Homelessness was associated with 0.7% (n = 469) of CD discharges and 0.9% (n = 415) of UC discharges. Mortality and endoscopy utilization rates were comparable between homeless and non-homeless patients with CD and UC. Surgical treatment was also broadly similar except for lower odds of bowel resection among homeless IBD patients with UC compared to domiciled IBD patients with UC (OR: 0.41, 95% CI: 0.20 to 0.84). Post-operative complications were also comparable except for lower rates of venous thromboembolism among homeless patients with CD (OR: 0.61, 95% CI: 0.38 to 0.97) whereas it was higher for homeless patients with UC (OR: 1.58, 95% CI: 1.08 to 2.30). Homeless IBD patients have comparable inpatient outcomes with non-homeless IBD patients.
Mungle T, Charu V, Okafor PN
HLA-DRB1*01:03 in patients with inflammatory bowel disease: a genotype-phenotype association study.★ The lancet. Gastroenterology & hepatology | 2026-06-15
The association between HLA-DRB101:03 and severe ulcerative colitis has long been recognised. However, the recent discovery of an association with neutralising auto-antibodies against IL-10 raises new questions about whether this haplotype contributes to other subphenotypes of inflammatory bowel disease (IBD). We sought to systematically reappraise the contribution of HLA-DRB101:03 across the full spectrum of IBD subphenotypes, including multiple disease-related adverse outcomes. In this genotype-phenotype association study, we used data from patients with IBD of inferred European ancestry from more than 100 UK hospitals who were recruited into the National Institute for Health and Care Research IBD BioResource or the UK IBD Genetics Consortium cohorts between 2005 and 2025. Associations between HLA-DRB101:03 and IBD phenotypes were examined using logistic or linear regression, and adjusted for sex, smoking, diagnosis, follow-up, genetic principal components, six co-inherited HLA alleles, and other significant associations. Time-to-event analyses were performed using Cox regression models. 43 762 patients with IBD (21 839 with Crohn’s disease and 21 923 with ulcerative colitis or IBD unclassified) were included in our analysis. HLA-DRB101:03 carriage was observed in 2009 (4·6%) patients with IBD and associated with multiple severe outcomes in the adjusted models, including colonic resection in patients with Crohn’s disease (odds ratio 1·35 [95% CI 1·07-1·69]), colectomy in patients with ulcerative colitis or IBD unclassified (1·99 [1·63-2·43]), perianal disease in both patients with Crohn’s disease (1·65 [1·42-1·92]) and patients with ulcerative colitis or IBD unclassified (1·70 [1·27-2·28]), and advanced therapy use in patients with Crohn’s disease (1·33 [1·12-1·58]) and patients with ulcerative colitis or IBD unclassified (2·17 [1·86-2·52]). HLA-DRB101:03 was associated with younger-onset ulcerative colitis or IBD unclassified and older-onset Crohn’s disease. HLA-DRB101:03 also associated with earlier development of perianal Crohn’s disease (hazard ratio 1·61 [95% CI 1·24-2·07]), earlier need for colonic surgery in patients with Crohn’s disease (1·43 [1·13-1·82]), and earlier colectomy in patients with ulcerative colitis or IBD unclassified (1·69 [1·33-2·14]). HLA-DRB101:03 carriers initiated advanced therapy earlier (HR 1·37 [95% CI 1·18-1·59] in patients with Crohn’s disease and 1·82 [1·53-2·16] in patients with ulcerative colitis or IBD unclassified) and had a higher risk of advanced therapy failure across IBD phenotypes (HR 1·23 [95% CI 1·02-1·50]). HLA-DRB101:03 emerges as a genetic determinant of severe disease in both patients with Crohn’s disease and patients with ulcerative colitis. Although further validation is needed, assessing HLA-DRB1*01:03 carriage might help identify patients who could benefit from more intensive monitoring or earlier use of advanced therapies, aiming to modify the disease course to which they are genetically predisposed. Wellcome Trust, the National Institute for Health and Care Research, the Medical Research Council, Open Targets, Crohn’s & Colitis UK, the Helmsley Charitable Trust, Crohn’s in Childhood Research Association, and AstraZeneca’s Centre for Genomics Research.
Zhang Q, Shakweh E, Sharip MT, Zare B, Roberts C, Wyatt NJ, Clough J, Bewshea C, Garwany OE, Lees R
Perioperative risk factors for disease recurrence following ileocecal resection in Crohn’s disease: implications for early immunosuppressive therapy. Updates in surgery | 2026-06-15
Crohn’s disease is a chronic inflammatory bowel disease (IBD) affecting 1.85-10.5 individuals per 100,000 per year. Approximately 30-50% of patients still require surgery during their lifetime. While patients with Crohn’s disease are at increased risk of postoperative complications, ileocecal resection remains a viable alternative to medical treatment for terminal ileitis. However, the optimal timing for initiating immunosuppressive therapy postoperatively, whether as a prophylactic measure or upon disease recurrence, remains a topic of debate. This study aimed to identify perioperative risk factors for disease recurrence to support a more tailored approach to early postoperative immunosuppressive therapy. A retrospective chart review was conducted on all patients who underwent ileocecal resection for Crohn’s disease between January 2006 and March 2023. The primary endpoint was the need for advanced medical therapy for Crohn’s disease within one year postoperatively. Secondary endpoints included clinical and endoscopic recurrence after one year and time to start advanced medical therapy, clinical recurrence and endoscopic recurrence. The following possible prognostic factors were analysed: age, sex, smoking status, BMI, presence of perianal disease, length of resection, advanced medical therapy, previous resection, previous appendectomy, behaviour classification, and disease extent. A total of 129 patients were included, with a median follow-up of 98 months. Higher BMI category was the most robust predictor for advanced medical therapy at one year (OR = 1.88, 95% CI [1.20-2.95], P = .006) and for time to endoscopic recurrence (HR = 1.62, 95% CI [1.21-2.16], P = .001). Previous bowel resection was significantly associated with advanced medical therapy on univariable analysis (OR = 3.25, 95% CI [1.39-7.61], P = .007), with a trend persisting in the multivariable model (OR = 2.49, P = .06). Perianal disease was associated with shorter medication-free survival (HR = 1.64, 95% CI [1.03-2.62], P = .04). Penetrating disease behaviour was linked to earlier start of advanced medical therapy on univariable analysis (HR = 1.60, 95% CI [1.02-2.50], P = .04). Female sex showed a trend toward a protective effect on clinical recurrence (OR = 0.47, P = .08). In this cohort, ileocecal resection was associated with substantial symptomatic improvement. To our knowledge, this study is the first to identify increased BMI as an independent risk factor. Furthermore, it suggests that perianal disease may be associated with increased recurrence risk, while female sex may be associated with lower risk. A more contemporary estimate of surgical reintervention after ileocecal resection for Crohn’s disease may be closer to 12% rather than the historically cited 35%, based on long-term follow-up in this cohort.
Depuydt M, Baert F, Bossuyt E, Gheskiere A, Lissens P, De Loof H, Pattyn P
Mechanisms of Inflammation in Post-Operative Recurrence of Crohn’s Disease.Review Journal of inflammation research | 2026-06-12
Despite advances in guideline-directed surveillance and initiation of biologic therapy after ileocecal resection for Crohn’s disease, many patients still experience post-operative recurrence. There is a growing field of research on the mechanisms of inflammation that are specific to post-operative recurrence after surgical resection and anastomosis. Within the innate immune system, certain genetic risk factors and an imbalance in matrix metalloproteinases have been implicated; however, the roles of specific innate immune cells are still being studied. Within the adaptive immune system, increased T-cell clonal expansion at the time of surgery and specific antibodies may play important roles in inflammation after resection. There are emerging associations to link mitochondrial oxidative stress, specific chemokines and cytokines, and microbial dysbiosis to the processes driving post-operative inflammation.
Greenwood H, Steiner CA, Click B
Anal fistulas: do classification systems predict surgical outcomes? Arquivos brasileiros de cirurgia digestiva : ABCD = Brazilian archives of digestive surgery | 2026-06-12
Anal fistulas remain challenging in colorectal surgery, with recurrence and postoperative incontinence common despite advances in treatment. Multiple classification systems exist, but their predictive value for surgical and functional outcomes is unclear. The aim of this study was to compare Parks, American Society of Colon and Rectal Surgeons (ASCRS), and St. James’s University Hospital (SJUH) MRI-based classifications in predicting surgical outcomes, including continence preservation. Retrospective analysis of 89 patients undergoing definitive surgical treatment for anorectal fistulas at a single referral center (2012-2019). Exclusions included rectovaginal fistulas, Crohn’s disease, or prior pelvic radiotherapy. Fistulas were classified using Parks, ASCRS, and, when available, SJUH (n=49). Outcomes included the number of procedures, type of initial procedure, fistula closure, and closure without continence deterioration. Continence was assessed using the Cleveland Clinic Jorge-Wexner score. Most fistulas were transsphincteric (Parks Type 2, 62%) and complex (ASCRS, 65%). Overall, 86.5% achieved fistula closure, and 73% achieved closure without continence deterioration. Parks and ASCRS were significantly associated with fistula closure with continence preservation (p=0.008 and 0.007, respectively) and type of initial procedure. Parks remained significant when considering closure alone (p=0.005), while ASCRS showed a borderline association (p=0.051). SJUH classification was associated only with procedure selection. Parks and ASCRS classifications were associated with fistula closure with continence preservation and type of initial procedure. Considering closure alone, only Parks remained significant. SJUH was limited to procedure selection. Overall, Parks and ASCRS guide surgical planning and prediction of functional outcomes, with Parks slightly more sensitive. Parks and ASCRS classifications are strongly associated with initial procedure choice and functional outcomes, including fistula closure with continence preservation. SJUH classification predicts only procedure selection. Parks appears slightly more sensitive, highlighting its value for surgical planning and anticipating postoperative function. Accurate classification of anal fistula is essential for guiding surgical strategies and counseling patient effectively. The Parks and ASCRS classification systems help predict which fistulas are likely to close successfully while preserving continence. Understanding the strengths and limitations of each system allows clinicians to select appropriate procedures, set realistic expectations, and facilitate shared decisionmaking. This approach ultimately improves outcomes in the management of complex anal fistulas. Fístulas anais são um desafio na cirurgia colorretal, com recorrência e incontinência pós-operatória frequentes. Diversos sistemas de classificação existem, mas seu valor preditivo para o tratamento e desfechos cirúrgicos ou funcionais permanece incerto. Comparar as classificações Parks, American Society of Colon and Rectal Surgeons (ASCRS) e St. James University Hospital (SJUH), baseada em ressonância magnética, quanto à predição de desfechos cirúrgicos e preservação da continência. Análise retrospectiva de 89 pacientes submetidos a tratamento cirúrgico definitivo de fístula anal (2012–2019). Foram excluídos pacientes com fístula retovaginal, doença de Crohn ou radioterapia pélvica prévia. Fístulas foram classificadas pelos sistemas Parks, ASCRS e SJUH (n=49). Desfechos incluíram número de procedimentos, tipo de procedimento inicial, fechamento da fístula e fechamento sem piora da continência. Continência pré e pós operatória avaliada pelo escore Jorge-Wexner. A maioria das fístulas era transesfincteriana (Parks Tipo 2, 62%) e complexa (ASCRS, 65%). O fechamento da fístula ocorreu em 86,5% e sem piora da continência em 73%. Parks e ASCRS associaram-se ao fechamento com preservação da continência (p=0,008 e p=0,007) e ao tipo de procedimento inicial. Parks manteve significância considerando apenas o fechamento (p=0,005), enquanto ASCRS apresentou associação limítrofe (p=0,051). SJUH associou-se apenas à escolha do procedimento inicial. Parks e ASCRS estiveram associadas ao fechamento da fístula com preservação da continência e ao tipo de procedimento inicial. Considerando apenas o fechamento, apenas Parks manteve associação significativa. SJUH esteve limitada à escolha do procedimento. No geral, Parks e ASCRS orientam planejamento cirúrgico e predição de desfechos, com Parks ligeiramente superior.
Hora JAB, Sobrado LF, Sobrado CW, Horvat N, Marques CFS, Ribeiro Junior U, Nahas SC
Cystic fibrosis-associated inflammatory bowel disease: a case series and literature review. Clinics and research in hepatology and gastroenterology | 2026-06-12
The management of inflammatory bowel disease (IBD) in patients with cystic fibrosis (CF) at risk of respiratory failure and severe lung infection is poorly described. The objective of this study was to describe the phenotype and evolution of IBD associated with CF, as well as the efficacy and tolerance of IBD treatments. A national, multicentre, descriptive, retrospective study was conducted. The study included all adult patients with a confirmed diagnosis of CF and IBD identified across participating GETAID centres. Disease characteristics and outcomes were retrieved from patient charts. A total of 10 cases with IBD associated with CF were identified (six male; median age at diagnosis, 32 years; 10 with Crohn’s disease (CD)). In CF, the DeltaF508 mutation was predominant; nine patients had lung involvement, and all had exocrine pancreatic involvement. Disease location and behaviour at diagnosis were similar to those observed in the general IBD population. During follow-up, four patients underwent surgery (40%), and nine patients were treated with immunosuppressants or biologics, resulting in clinical remission for 50% and 66%, respectively. Two patients with severe CF co-colonised with Pseudomonas Aeruginosa and Staphylococcus aureus experienced severe lung infection. Patients with CF are more likely to have CD than ulcerative colitis. In patients with advanced CF, the potential infectious risks associated with IBD therapies require individualised assessment.
Rochereau A, Treton X, Bourrier A, Abitbol V, Serrero M, Nancey S, Kervégant AG, Belleguic C, Bouguen G
Endoscopic Management of Pouch Volvulus as a Complication of Ileal Pouch Anal Anastomosis in Patients With Ulcerative Colitis.Case report ACG case reports journal | 2026-06-11
Pouch volvulus is a rare but potentially morbid complication after total proctocolectomy with ileal pouch anal anastomosis, typically managed surgically. Evidence for definitive endoscopic therapy is limited. We report 2 patients with ulcerative colitis who developed pouch volvulus after ileal pouch anal anastomosis and were poor surgical candidates due to medical complexity. Both underwent successful endoscopic detorsion; 1 required adjunctive endoscopic decompression with temporary tube placement. Symptoms resolved without ischemia, and no recurrence occurred through 6 months of follow-up. These cases suggest endoscopic detorsion can be a safe, diagnostic, and definitive management option for complex patients with viable pouch mucosa.
Kareddy V, Ioannou S, Deshpande AR
Advanced phenotypes and favorable 1-year outcomes with accelerated step-up strategy in newly diagnosed inflammatory bowel disease in a tuberculosis-endemic, resource-constrained setting. Therapeutic advances in gastroenterology | 2026-06-09
The incidence of inflammatory bowel disease (IBD) is rising across Southeast Asia, yet real-world data on clinical phenotypes, treatment strategies, and outcomes in tuberculosis (TB)-endemic, resource-constrained settings remain scarce. To characterize disease phenotypes, treatment utilization, and 1-year outcomes in a Vietnamese inception cohort of newly diagnosed IBD patients in a tuberculosis-endemic, resource-constrained setting. Single-center, hybrid retrospective-prospective inception cohort study. Consecutive adults diagnosed with Crohn’s disease (CD) or ulcerative colitis (UC) at a tertiary referral center in Ho Chi Minh City, Vietnam, between June 2019 and June 2024. A Baseline Cohort (N = 126) was analyzed for phenotypic characterization. Patients completing ⩾12 months of follow-up comprised the Outcome Cohort (N = 66) for assessment of treatment patterns and clinical, biochemical, and endoscopic outcomes. Treatment followed an accelerated step-up strategy with originator anti-tumor necrosis factor (TNF) agents (infliximab/adalimumab) after mandatory TB screening. Among 126 patients (80 CD, 46 UC), CD was characterized by substantial diagnostic delay (median 12 months), with 57.6% presenting stricturing or penetrating behavior and 25.0% having undergone intestinal resection before IBD confirmation. Extensive colitis (E3) predominated among UC patients (63.0%), and 78.3% had moderate-to-severe disease. Anti-TNF utilization increased from 13.6% within the first 2 months after diagnosis to 45.5% at 1 year. In the Outcome Cohort (N = 66), steroid-free clinical remission was achieved in 63.6%, and mucosal healing was documented in 62.3% of endoscopically evaluated patients. Serious infections occurred in 9.1%, with TB reactivation in 4.5%. IBD in Vietnam presents with diagnostic delays, complicated phenotypes, and high surgical rates at initial presentation. Despite these challenges, an accelerated step-up strategy with early anti-TNF escalation was associated with favorable 1-year steroid-free remission and mucosal healing rates. These findings suggest that treat-to-target care with early biologic escalation may be feasible in selected patients in TB-endemic, resource-constrained settings, provided that structured TB monitoring is implemented. Successful one-year treatment of severe, newly diagnosed inflammatory bowel disease in Vietnam using early, strong medications despite high tuberculosis risks Inflammatory bowel disease (IBD) is becoming more common in Southeast Asia, including Vietnam. However, diagnosing it is difficult because its symptoms are very similar to intestinal tuberculosis (TB), a common infection in the region. Because of this confusion, patients often suffer for a long time—sometimes up to a year—before finding out they have IBD. By the time they are properly diagnosed, their disease is often severe, and some even require surgery before receiving the correct diagnosis. In this study, we looked at 126 adults newly diagnosed with IBD at a major hospital in Vietnam. We wanted to see if treating them quickly with strong, advanced medications (known as biologics) would be safe and effective. We found that this treatment approach was associated with encouraging one-year outcomes. After one year of treatment, about 64% of the patients felt completely well without needing to take steroid medications. Furthermore, tests showed that the inside of the intestines had healed completely in 62% of the patients. However, because these strong medications can lower the body’s immune defenses, we carefully tested everyone for TB before starting treatment. Even with negative initial TB tests, 4.5% of patients still developed TB later. This highlights that ongoing monitoring for tuberculosis may be important throughout the course of biologic treatment, rather than relying solely on a single test before starting therapy.
Dinh TH, Dang LM, Nguyen CD, Vo DT, Huynh TM, Vo TD, Bui HH, Quach DT
A systematic review of the methodological quality of randomised trials in IBD surgery.Systematic review Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland | 2026-06
This systematic review aimed to evaluate the design, statistical robustness and real-world applicability of randomised controlled trials in IBD surgery. A systematic review of RCTs involving adult patients with IBD undergoing surgical interventions was conducted. Databases and registries were searched from 2005 to 2025. Dual screening and extraction were performed. Trials were appraised using RoB-2, PRECIS-2 and fragility index. The study was registered with PROSPERO (CRD420251058758). From 5803 abstracts, 18 published RCTs and 26 registered but unpublished trials were identified. Published RCTs had a median planned sample size of 102 participants (IQR 80-143) and recruited a median of 89 (IQR 55-114), with frequent under-recruitment (7/18, 39%) and early termination (5/18, 28%). Methodological appraisal revealed that most studies (12/18, 67%) had some concern for bias on RoB-2 assessment. PRECIS-2 evaluation showed a tendency towards pragmatic designs. The median fragility index was 3 (IQR 1-6). Of registered, unpublished trials, median planned sample size was 155 (IQR 93-196), with the largest study having a planned enrolment of 550 participants. Surgical RCTs in IBD face challenges across design and delivery, such as modest sample sizes, under-recruitment and statistical fragility. The findings from this review highlight the importance of larger, multicentre and collaborative trials to strengthen the evidence base in IBD surgery.
Aimar K, Gaur A, Peirson M, Walshaw J, Pinkney TD, Lee MJ
Authors’ reply: Therapeutic management and risk of colectomy in patients with acute severe ulcerative colitis and previous exposure to anti-tumor necrosis factor drugs: a comparative study of GETECCU.Editorial★ Journal of Crohn’s & colitis | 2026-06
Abstract not available.
Mesonero F, Zabana Y, Gutiérrez A
Quality of Life & PROs (11 papers)
Membranous nephropathy secondary to very early-onset inflammatory bowel disease in a 3-year-old boy: case report.Case report CEN case reports | 2026-06-19
Membranous nephropathy (MN) is uncommon in children overall, but secondary MN is relatively common in younger children. Inflammatory bowel disease (IBD) can be complicated by kidney disease, but IBD complicated by MN is rarely reported. A 3-year-old boy diagnosed with very early onset IBD (VEO-IBD) a year earlier was incidentally found to have proteinuria via urine screening system. Laboratory tests revealed nephrotic syndrome with microscopic hematuria and signs of ongoing inflammation associated with IBD activity. Kidney biopsy showed mesangial cell proliferation and dense subepithelial immune complex deposits, along with negative PLA2R staining, which supported a diagnosis of secondary MN. Oral steroid therapy was initiated for its potential benefit for both nephrotic syndrome and the underlying VEO-IBD. As a result, four months later, proteinuria and hematuria had resolved, and kidney function remained stable. This is the youngest reported patient with MN associated with IBD. Routine urinalysis is suggested by this case to be useful for detecting kidney complications of IBD, including MN. Moreover, steroid therapy is likely to be useful for MN secondary to IBD. Our report suggests that potential kidney complications should also be considered in patients with VEO-IBD.
Aoyama S, Yamamura T, Horinouchi T, Kimura Y, Inoki Y, Sakakibara N, Nagano C, Ishimori S, Kameoka Y, Kajihara K
Associations of dietary habits and meal regularity with gastrointestinal symptoms, depression, and quality of life in patients with inflammatory bowel disease: a cross-sectional study. BMC gastroenterology | 2026-06-17
Inflammatory Bowel Disease (IBD) is a chronic and recurrent gastrointestinal disorder that adversely affects patients’ quality of life. The influence of daily dietary behaviors and meal regularity on gastrointestinal symptoms and quality of life remains under-investigated. The study aimed to evaluate dietary intake, dietary habits, and meal patterns of the IBD patients and based on this data, to determine their gastrointestinal symptoms, quality of life, and depression status. This cross-sectional study was conducted at Istanbul University Cerrahpaşa Medical Faculty Hospital and included adults aged 18-75 years with a confirmed diagnosis of IBD attending routine outpatient follow-up visits. Data were collected using a sociodemographic and clinical data form, a 24-Hour Dietary Recall, IBD Quality of Life Questionnaire (IBD-QoL), Beck Depression Inventory II (BDI-II), Gastrointestinal Symptom Rating Scale (GSRS). A total of 50 patients with IBD were included (30 Crohn’s disease and 20 Ulcerative colitis). The mean age was 39.5 ± 13.49 years and the mean BMI was 24.82 ± 5.39 kg/m². Most patients (82%) reported consuming foods that worsened their symptoms, primarily legumes (21%), milk (14.3%), and raw vegetables (10.9%). Conversely, 50% identified foods that alleviated symptoms, mainly yogurt (18.2%) and cooked vegetables (18.2%), cooked meat (7.6%). Dietary analysis revealed intake below recommended levels for fiber, vitamins B1, B2, B6, C, folate, potassium, calcium, magnesium, and iron. Meal skipping was reported by 20% of patients with Ulcerative colitis and 40% with Crohn’s disease. Patients who skipped meals had higher gastrointestinal symptom scores than those with regular meal patterns. Additionally, higher depression scores were associated with lower quality of life and more severe gastrointestinal symptoms. The study found that dietary intake and meal patterns in individuals with IBD are associated with their quality of life and gastrointestinal symptoms. A balanced and regular diet may be associated with reduced gastrointestinal symptoms and improved quality of life in IBD patients.
Özen EN, Hatemi Aİ
Mediating effect of health anxiety in patients with inflammatory bowel disease between disease perception and self-management behavior. Scientific reports | 2026-06-16
This study aimed to examine the mediating role of health anxiety in the relationship between illness perception and self-management behavior among individuals with inflammatory bowel disease(IBD). A total of 326 patients with IBD who were treated at our hospital between June 2023, and June 2025 were enrolled. Data were collected using a general information questionnaire, the Brief Illness Perception Questionnaire (BIPQ), the Short Health Anxiety Inventory (SHAI), and the IBD Self-Management Behavior Scale. Among the 326 participants, the mean BIPQ, SHAI, and self-management scores were 47.31 (SD = 12.71), 28.89 (SD = 8.81), and 67.79 (SD = 20.48), respectively. Self-management scores were significantly lower among patients older than 60 years and those with a disease duration of more than five years, whereas higher scores were observed among patients with a monthly income greater than 5,000 yuan (all P < 0.05). BIPQ scores were negatively correlated with self-management behavior (r = -0.660) and positively correlated with SHAI scores (r = 0.417). SHAI scores were negatively correlated with self-management behavior (r = -0.501). Mediation analysis showed that the BIPQ scores had both a direct negative association with self-management behavior (coefficient = -1.180, accounting for 82.69% of the total effect) and an indirect association mediated through health anxiety (coefficient = -0.246, accounting for 17.31% of the total effect). The 95% bias-corrected bootstrap confidence interval for the indirect effect did not include zero. Patients with IBD in this cohort exhibited predominantly negative illness perceptions, elevated health anxiety, and suboptimal self-management behaviors. The findings suggest that illness perception is associated with self-management behavior both directly and indirectly through the mediating role of health anxiety. These cross-sectional findings suggest the potential value of integrating psychological assessment and intervention into routine IBD care to improve patient self-management and long-term health outcomes. However, causal inferences cannot be drawn from the present data.
Wang R, Wang Y, Zhou X, Liu J
Corrigendum to “Exploring the mechanism of Sinisan in the treatment of ulcerative colitis with depression based on UPLC-Q-Orbitrap-MS combined with network pharmacology, molecular docking, and experimental validation” [J. Ethnopharmacol. (2025) (347) 119696]. Journal of ethnopharmacology | 2026-06-16
Abstract not available.
Zheng M, Liu H, Zhang R, Guo X, Shao Q, Zhang J, Li L, Wang J, Miao S, Shi X
Caregiver contribution to patient self‑care and quality of life among informal carers of adult patients with inflammatory bowel disease: a cross‑sectional study.Multicenter study Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation | 2026-06-15
Informal caregivers play a critical role in the management of adult patients with inflammatory bowel disease (IBD), yet the association between their contribution to patient self-care and their own health-related quality of life (HRQoL) remains underexplored. This study aimed to examine the cross-sectional association between caregivers’ contribution to patient self-care and caregivers’ physical and mental HRQoL. A multicentre cross-sectional study was conducted across nine IBD centres in Italy. Caregiver contribution to patient self-care was assessed using the Caregiver Contribution to Self-Care of Chronic Illness Inventory (CC-SC-CII), including Maintenance, Monitoring, and Management domains. HRQoL was measured using the 12-Item Short Form Survey, yielding Physical Component Summary (PCS-12) and Mental Component Summary (MCS-12) scores. Generalized Additive Models were used to estimate potential non-linear associations between CC-SC-CII domains and HRQoL. The study included 275 informal caregivers. No statistically supported associations were observed between CC-SC-CII Maintenance, Monitoring, or Management and PCS-12. For MCS-12, only CC-SC-CII Maintenance showed a statistically supported non-linear association (edf = 4.34, F = 2.21, p = 0.018; adjusted R2 = 0.272; deviance explained = 38.1%). The model-estimated MCS-12 difference between the 75th and 25th percentiles of CC-SC-CII Maintenance was 6.58 points (95% CI 1.50-11.70). No statistically supported associations were observed for CC-SC-CII Monitoring or Management and MCS-12. Caregiver contribution to patient self-care maintenance was associated with caregivers’ mental, but not physical, HRQoL. The findings should be interpreted as exploratory associations and require confirmation in longitudinal dyadic studies including both caregiver- and patient-reported outcomes.
Napolitano D, Gonzalo MFM, Cascio AL, Benedetti F, Povoli A, Sanità T, Suriano V, Lorenzon G, Luongo A, Zaetta D
In vitro modeling of inflammatory bowel diseases using a newly developed immunocompetent colon epithelial monolayer co-culture model. npj biomedical innovations | 2026-06-15
Clinical treatment of inflammatory bowel diseases (IBD) remains challenging due to the complex interplay between the epithelial barrier, immune system, and gut microbiota. While in vitro models are pivotal for studying barrier dysfunction, developing a standardized and functionally relevant system for IBD remains challenging. To overcome this, we established an immunocompetent murine colon epithelium monolayer to model IBD-like conditions. Colons from wild-type mice were digested into single cells and seeded onto Matrigel-coated transwells. Within seven days, monolayers showed strong barrier properties and displayed epithelial cell lineage, including goblet, stem, and enteroendocrine cells. However, exposure to pro-inflammatory cytokines as well as infection with pathogenic bacteria, including Clostridium rodentium and Salmonella Typhimurium, disrupted epithelial integrity. To better reflect the in vivo state, polarized T cells and macrophages were co-cultured with the epithelium. Pro-inflammatory Th1 and Th17 cells impaired barrier function, while M0 and M2 macrophages maintained it, representing both homeostatic and disrupted conditions of the gut. Upon Salmonella Typhimurium infection, M1 macrophages produced IFN-γ, and M2 macrophages secreted IL-10 and enhanced ZO-1 expression. Overall, our model presents a promising platform to study epithelial barrier dysfunction, immune-epithelial cross-talk, and host-pathogen interactions, offering valuable insights into IBD mechanisms and potential therapeutic approaches.
Larafa I, Zogorean R, Buehler A, Günther C, Wirtz S, Neurath MF, Thoma OM, Waldner MJ
[Gly2]-GLP-2(1-5)：An Ultra-Short GLP-2 Peptide for Intestinal Mucosal Protection in Inflammatory Bowel Disease. Peptides | 2026-06-12
Inflammatory bowel disease (IBD) is a disorder characterized by defective intestinal barrier function, aberrant over-apoptosis of intestinal epithelial cells, and constitutive activation of pro-inflammatory signaling pathways. Glucagon-like peptide-2 (GLP-2), an endogenous gastrointestinal hormone, is known to exert protective effects against IBD by repairing the intestinal barrier and suppressing inflammatory responses. This study used molecular docking and molecular dynamics simulations to discover that [Gly2]-GLP-2(1-5) has a high binding affinity and strong binding stability with GLP-2R. In DSS-induced colitis mouse model, treatment with [Gly2]-GLP-2(1-5) can effectively reverse weight loss in mice, reduce disease activity index, increase colon length, and alleviate inflammatory damage in colon tissues; it also upregulates the expression of tight junction proteins, inhibits epithelial cell apoptosis and release of inflammatory factors, and enhances the regenerative ability of organoids. In LPS-stimulated intestinal epithelial cells, [Gly2]-GLP-2(1-5) can promote intestinal epithelial cell migration, maintain the integrity of tight junctions, and inhibit cell apoptosis. These findings suggest that [Gly2]-GLP-2(1-5) may be the shortest active short peptide of GLP-2 and is expected to be an effective peptide for the treatment of inflammatory bowel disease.
Liu H, Li W, Ni C, Jing S, Liu J, Zhao Y
ROS-Triggered Self-Aggregation of a β-Elemene Olefin-Rich Nanoemulsion for Mitochondrial-Targeted Metabolic Reprogramming and Colitis Inflammation Alleviation. International journal of nanomedicine | 2026-06-08
Inflammatory bowel disease (IBD) is a chronic condition driven by pro-inflammatory macrophages. Although natural compounds with carbon-carbon double bonds (C=C bonds), such as β‑elemene, exhibit anti-inflammatory properties, their precise subcellular targets and mechanisms remain elusive. This study aimed to develop a targeted nanomedicine to elucidate the anti-inflammatory mechanism of β‑elemene and establish a novel therapeutic strategy for colitis. We engineered a reactive oxygen species (ROS)-responsive β‑elemene nanoemulsion (ELE-NE) for targeted drug delivery. Its therapeutic efficacy and mechanism were evaluated in a murine model of dextran sulfate sodium (DSS)-induced colitis. A mitochondria-targeted, ROS-activatable near-infrared probe was also developed for in vivo imaging tracking of inflammatory foci and assessment of therapeutic efficacy. In DSS-induced colitis mice, ELE-NE preferentially accumulated in inflamed colon tissue and effectively alleviated disease pathology. Mechanistically, upon reaching inflammatory macrophages, ELE-NE utilized the pathological ROS surge to undergo spatially confined aggregation at mitochondrial sites. This nano-aggregation directly disrupted the electron transport chain (ETC), potently suppressing oxidative phosphorylation and reprogramming cellular energy metabolism. Consequently, this mitochondria-focused metabolic intervention attenuated M1 macrophage polarization, reduced pro-inflammatory cytokine secretion. This is the first report demonstrating that β‑elemene acts via ROS‑triggered mitochondrial aggregation and metabolic reprogramming. We deciphered the mechanism of β-elemene, revealing that its olefinic (C=C) functional group enables bioresponsive mitochondrial aggregation and metabolic reprogramming, thereby proposing the concept of “olefinic drugs” as a distinct therapeutic class. Furthermore, we established a novel theranostic paradigm for treating inflammatory diseases using olefinic nanomedicines, enabled by a companion imaging tool for non‑invasive detection of inflammatory foci and dynamic monitoring of the treatment process.
Luo Z, Jia L, Tang Y, Huang Y, Ma Z, Li Y, Zhang X, Zhang P, Xie T
Gut microbiota alterations associated with anxiety and depression in inflammatory bowel disease: a systematic review of prospective cohorts and randomized trials.Systematic review Frontiers in microbiology | 2026-06-02
Anxiety and depression are highly prevalent among patients with inflammatory bowel disease (IBD) and are closely associated with reduced quality of life and poor treatment adherence. The gut-brain axis has been proposed as a key mechanistic framework, with the gut microbiota playing a central role. However, findings from clinical studies remain inconsistent, and a comprehensive synthesis of the evidence is lacking. This systematic review aimed to integrate evidence from randomized controlled trials (RCTs) and prospective cohort studies to evaluate the associations between gut microbiota characteristics, microbiota-targeted interventions, and symptoms of anxiety and depression in patients with IBD. A systematic search was conducted in PubMed, Embase, the Cochrane Library, Web of Science, EBSCOhost, and Scopus. The search covered records from database inception to October 17, 2025. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A descriptive synthesis approach was used to summarize the findings. Study quality was assessed using the Critical Appraisal Skills Programme (CASP) checklist. Ten studies were included, comprising six prospective cohort studies and four RCTs. These studies included a total of 1,040 patients with IBD. Cohort studies consistently showed that anxiety and depressive symptoms were associated with reduced microbial α-diversity, enrichment of pro-inflammatory taxa, and depletion of short-chain fatty acid (SCFA)-producing bacteria. These associations persisted after adjustment for inflammatory markers. They were also observed when analyses were restricted to patients in remission. This suggests that the associations may not be fully explained by disease activity. Evidence from RCTs showed that microbiota-targeted interventions, including probiotics and fecal microbiota transplantation, modulated microbial composition and reduced anxiety and depression scores. Studies combining psychological interventions with microbiota profiling also suggested potential effects on gut microbial composition. However, the findings remain heterogeneous. Current evidence supports a close and potentially bidirectional association between gut microbiota dysbiosis and anxiety and depression in patients with IBD. Both microbiota-targeted interventions and psychological therapies may represent promising strategies for managing psychological comorbidities in IBD. Future large-scale, standardized longitudinal studies and randomized controlled trials are warranted to clarify directionality, test causal hypotheses, and develop personalized intervention approaches. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD420251166542.
Zhang T, Wang L, Ren Z, Man R, Cheng X, Wang L, Wang J, Bu X, Yu Y
Gastrointestinal symptom-specific anxiety is associated with disability in inflammatory bowel diseases independent of general anxiety and self-reported disease activity: evidence from a large cross-sectional patient study.★ Journal of Crohn’s & colitis | 2026-06
Gastrointestinal symptom-specific anxiety (GSA) is increasingly recognized as an important construct in the disease experience of inflammatory bowel diseases (IBD). However, it remains unclear to what extent GSA overlaps with general anxiety in the IBD population, and whether it is associated with disability beyond general anxiety and other clinical and demographic variables. First, we examined how many patients with elevated GSA do or do not experience general anxiety, and vice versa. Second, we assessed the unique contribution of GSA to variance in IBD-related disability, keeping general anxiety, disease activity, and other variables constant. In a cross-sectional survey study, over 1000 IBD patients completed questionnaires on general anxiety (the anxiety subscale of the Hospital Anxiety and Depression Scale [HADS]), GSA (the Visceral Sensitivity Index [VSI]), IBD-related disability (the IBD Disk), and self-reported clinical disease activity (Patient-Reported Outcomes [PRO] and Manitoba IBD Index [MIBDI]) alongside a set of general demographic and clinical questions. GSA and general anxiety frequently co-occurred, but 38.0% of patients reported GSA without general anxiety. Additionally, GSA was significantly associated with IBD-related disability (P < .001) even when general anxiety, disease activity, and other variables were controlled for. Although general anxiety showed the strongest association with disability (β = .27), the association for GSA (β = 0.22) was stronger than for clinical disease activity (β = .18) and other demographic and clinical variables. Overall, this highlights the clinical significance of GSA beyond general anxiety and disease activity in IBD.
Van den Borren S, Guadagnoli L, Teugels A, van den Eijnden I, Keersmaekers B, Ferrante M, Van Diest I
Inflammatory bowel disease must be a policy priority after the 2025 United Nations declaration on non-communicable diseases and mental health.★ Journal of Crohn’s & colitis | 2026-06
The 2025 United Nations Political Declaration on non-communicable diseases (NCDs) and mental health provides a critical opportunity to recognize inflammatory bowel disease (IBD) as part of the global NCD agenda. Once confined to the West, IBD now affects over 7 million people worldwide, with the steepest rise in South Asia, Latin America, and Africa. Its early onset, chronic relapsing course, psychosocial burden, and economic cost align it closely with major NCDs. Yet, policy recognition remains limited, particularly in low- and middle-income countries, where diagnostic delays, inequitable access to advanced therapies (biologics and small molecules), and catastrophic healthcare costs persist. Integrating IBD into national NCD frameworks, universal health coverage schemes, and essential drug lists would advance Sustainable Development Goals. The Declaration’s emphasis on mental health is especially relevant, as anxiety and depression affect nearly 40% of IBD patients, influencing disease activity and outcomes. Embedding psychosocial care, primary care training, and research equity into IBD programs will foster patient-centered, resilient health systems. Recognizing IBD within the NCD continuum is both a moral and policy imperative, essential to achieving equitable, integrated, and sustainable chronic disease care in the 21st century.
Singh A, Bhardwaj A, Midha V, Sood A
Pathogenesis & Basic Science (8 papers)
Oridonin ameliorates ulcerative colitis by regulating the PI3K/AKT/mTOR signaling pathway to activate autophagy. International journal of molecular medicine | 2026-06-19
The present study aimed to investigate the therapeutic effects and underlying mechanism of oridonin (ORI) in ulcerative colitis (UC) using the lipopolysaccharide (LPS)‑induced macrophage inflammatory model in vitro and the dextran sulfate sodium (DSS)‑induced mouse UC model in vivo. Cell Counting Kit‑8 assay was used to determine the appropriate drug concentrations for the in vitro experiments. Western blotting and reverse transcription‑quantitative polymerase chain reaction were performed to evaluate the expression levels of proteins and mRNAs related to signaling pathways, autophagy and inflammatory cytokines. The autophagy inhibitor 3‑methyladenine was applied to verify the role of the PI3K/AKT/mTOR pathway. In vivo, the disease activity index (DAI) was recorded and colon tissue damage was assessed by hematoxylin and eosin staining. Serum inflammatory cytokines were measured using an enzyme‑linked immunosorbent assay. Network pharmacology based on GeneCards and Traditional Chinese Medicine Systems Pharmacology databases, along with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis, predicted involvement of the PI3K/AKT/mTOR pathway in the pathogenesis of UC, which was further validated by the immunohistochemistry, immunofluorescence and western blotting of colon tissues. The results indicated that ORI significantly reduced the expression of pro‑inflammatory cytokines and increased the anti‑inflammatory cytokine interleukin‑10 in LPS‑stimulated macrophages. In DSS‑induced colitis mice, ORI treatment alleviated body weight loss, decreased DAI scores, improved colon shortening and upregulated the expression of intestinal tight junction proteins. Mechanistically, ORI inhibited the PI3K/AKT/mTOR pathway and altered autophagy‑related molecular markers, as evidenced by increased levels of autophagy‑related (ATG)13, beclin‑1, ATG12, ATG7 and ATG5 as well as decreased expression of p62. In conclusion, ORI alleviates inflammatory responses in vitro and mitigates UC‑related pathological changes in vivo, which may be associated with suppression of the PI3K/AKT/mTOR pathway and modulation of autophagy‑associated protein markers.
Miao Z, Liu B, Zhou X, Lu M, Jia N, Zhang H, Qi Y, Tan X, Zhang Q
An Attention-Enhanced ViT-HLNN Hybrid Ensemble Framework for Multi-Class Gastrointestinal Disease Classification. Scientific reports | 2026-06-19
Gastrointestinal (GI) diseases such as polyps, esophagitis, and ulcerative colitis pose significant diagnostic challenges due to subtle visual patterns. Early, accurate, and scalable diagnostic tools are essential for improving outcomes and streamlining care. In this study, we propose a hybrid deep learning framework for multi-class GI disease classification that integrates a Vision Transformer (ViT) with a Hierarchical Long-Short-Term-Memory Neural Network (HLNN), further enhanced through ensemble learning using Bagging and Stacking. This hybrid architecture captures both global dependencies and local spatial-temporal features in endoscopic imagery, enabling precise multi-class classification. The model was trained and validated on the Kvasir-v2 dataset, comprising over 8000 labelled endoscopic images across eight GI disease classes. The proposed method achieved up to 99.99% accuracy on the test set and 99.96% mean accuracy across tenfold cross-validation, with macro F1-scores exceeding 0.999, and Cohen’s kappa of 0.994, indicating excellent agreement. Test set performance was evaluated on a fixed, class-stratified held-out test set (100 images per class) and reported as the mean across multiple training runs with different random seeds, ensuring statistical robustness. In comparative analysis, we demonstrated that the proposed hybrid model outperforms established baselines, including ViT-only, MobileNet-V2, EfficientNet-B0, ResNet-101, and NASNet-Large. Controlled ablation studies validate the individual and combined contributions of HLNN and ensemble strategies. Robustness was further confirmed under Gaussian noise, motion blur, and illumination shifts, with accuracy consistently above 96%. Zero-shot external evaluation on the independent GastroVision dataset and class-holdout testing on the held-out Polyps class further demonstrate generalization beyond the Kvasir-v2 training distribution. Robustness of Grad-CAM explanations was validated through a sanity check, correlation r = 0.91, and focused attention entropy 0.32, confirming stability under perturbations. These results highlight the potential of the proposed framework for robust and interpretable GI image classification.
Abdullah, Ather MA, Fatima Z, Rodríguez JLO, Sánchez-Mejorada CG, Téllez RQ, Ruiz MJT
Betulinic Acid Enema Alleviates Colitis by Targeting Vitamin D Receptor to Protect the Intestinal Mucosal Barrier and Modulate Mucosa-Associated Microbiota. Phytotherapy research : PTR | 2026-06-18
Ulcerative colitis (UC) is a chronic inflammatory disease of the colon with limited effectiveness and safety of current drug therapies. Betulinic acid (BA) is a naturally occurring pentacyclic triterpenoid present in traditional Chinese medicines used clinically as retention enemas for UC, but its direct effects and mechanisms remain unclear. This study evaluated the therapeutic impact of BA enema in dextran sulfate sodium (DSS)-induced colitis by monitoring disease activity index (DAI), colon length, and histopathology, and by assessing inflammatory cytokines, mucosal tight junction, and mucin-2 (MUC2) expression. Colonic mucosa-associated microbiota were profiled by 16S rRNA gene sequencing. Potential BA targets were predicted using Swiss Target Prediction and validated by molecular docking, molecular dynamics simulations, cellular thermal shift assay, and biolayer interferometry. The functional relevance of the vitamin D receptor (VDR) was examined using a VDR antagonist in vivo and in vitro, and transcriptomic datasets from UC patients were analyzed to define VDR expression patterns. BA enema markedly attenuated DSS-induced colitis, such as reducing the DAI, inhibiting colonic damage, and improving colon length shortening. The BA also significantly restored the tight junction proteins, associated mucin proteins, and mucin-2 (MUC2). The BA reduced potentially pathogenic bacteria in the colonic mucosa. In addition, BA significantly restored the VDR proteins, and the VDR antagonist weakened the effects of BA in vivo and in vitro. The binding site between VDR and BA was Trp286. Transcriptomic analyses confirmed VDR downregulation in UC. These findings indicate that BA enema alleviates experimental colitis in part by targeting VDR to protect the intestinal mucosal barrier and modulate mucosa-associated microbiota, supporting BA as a promising candidate for UC treatment.
Dong L, Gao Y, Li Q, Chen G, Yang D, Zhao L, Liu X, Lin S
Timing-dependent protective and therapeutic effects of ethyl pyruvate in trinitrobenzene sulfonic acid-induced experimental colitis. Experimental physiology | 2026-06-17
Ulcerative colitis (UC) involves excessive inflammation, extracellular matrix remodelling and oxidative stress. Ethyl pyruvate (EP) exhibits anti-inflammatory effects, but the comparative efficacy of prophylactic versus therapeutic administration and timing-dependent molecular responses remains unclear. The objective of this work was to evaluate timing-dependent protective and therapeutic effects of EP in trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis, focusing on inflammatory mediators, matrix metalloproteinases (MMPs), oxidative status and gene expression. Rats were randomly assigned to Control, EP, Colitis, Pre-colitis (EP before TNBS) and Post-colitis (EP after TNBS) groups. Colonic injury was assessed macroscopically and histopathologically. Tissue levels of matrix metalloproteinase (MMP)-2, MMP-9, interleukin (IL)-1, IL-17, IL-10, nuclear factor-κB (NF-κB), inducible nitric oxide synthase (iNOS) and total antioxidant capacity (TAC) were measured using ELISA kits. Gene expression of MMP-9, cytokines, NF-κB, high mobility group box 1 (HMGB1), iNOS and interferon-γ was analysed by quantitative real-time PCR. TNBS induced severe colonic injury with upregulation of pro-inflammatory cytokines, NF-κB signalling, MMP-2/9 and oxidative imbalance (P < 0.01). EP attenuated tissue damage in both prophylactic and therapeutic settings. Post-colitis (therapeutic) EP administration produced greater suppression of MMP-2, MMP-9, NF-κB, HMGB1 and iNOS, along with superior restoration of TAC (P < 0.05), indicating timing-dependent modulation of inflammatory and matrix degradation pathways. EP exerts both preventive and therapeutic effects in TNBS-induced colitis by suppressing inflammatory signalling, regulating extracellular matrix remodelling and enhancing antioxidant defences. Therapeutic administration is more effective than prophylactic treatment, highlighting the importance of timing in optimizing EP’s efficacy in inflammatory bowel disease.
Yorulmaz H, Yorulmaz E, Özkök E, Küçük SH, Sünger E, Ebrahimi A, Yılmaz B, Altınay S
Corrigendum to “Oleanolic acid 28-O-β-D-glucopyranoside alleviates TNBS-induced ulcerative colitis in rat by regulating Nrf2/x-CT/GPX4-mediated ferroptosis” [Journal of Ethnopharmacology 353 (2025) 120369]. Journal of ethnopharmacology | 2026-06-16
Abstract not available.
Wang C, Li Z, Liu L, Jia W, Geng X, Liu H, Wang C, Wu Y, Lin H, Liu J
Enhancing the Efficacy of Ulcerative Colitis Treatment by Inhibiting LCN2-Mediated Pyroptosis Through Traditional Processing Techniques: With the rhizome of Atractylodes macrocephala Koidz. as an Example. Journal of ethnopharmacology | 2026-06-16
Atractylodes Macrocephala Rhizome (AMR), the dried rhizome of Atractylodes macrocephala Koidz (family Asteraceae), is a commonly used Chinese herbal medicine for treating ulcerative colitis (UC) and has extensive applications in both Traditional Chinese Medicine (TCM) and modern medicine. The therapeutic effects of its distinctive processed variety, rice-washed water processed Atractylodis Macrocephalae Rhizoma (Migan Shui Piao Baizhu, R-AMR), have yet to be reported, and its potential mechanisms of action require further exploration. This study aims to compare the therapeutic effects of R-AMR and raw AMR on UC mice and further explore their mechanisms of action, thereby providing insights into the processing mechanism of AMR using rice-washed water. Firstly, a DSS-induced mouse UC model was established in vivo. The efficacy of treatment with rice-washed water processed AMR in improving UC was evaluated by DAI scores, histopathological changes, serum inflammatory cytokines, tight junction proteins (ZO-1, Claudin-1), and mucin (MUC2) levels. Then, bioinformatics, machine learning, and molecular docking were integrated to identify core disease targets and explore the mechanism of R-AMR in treating UC. Nextly, an LPS-induced UC cell model was established using NCM460 cells, and LCN2 siRNA-transfected cell experiments were conducted. The biological effects and mechanisms of action of key targets were validated in vitro through immunofluorescence, WB, and RT-qPCR techniques. Finally, we validated the roles of the above-identified pathways in the treatment of UC with AMR through in vivo experiments. In in vivo efficacy experiments, both R-AMR and raw AMR effectively reduced DAI scores and histopathological scores in UC mice. They downregulated proinflammatory factors and upregulated anti-inflammatory factors while increasing tight junction protein expression (ZO-1, Claudin-1) to restore damaged intestinal epithelial mucosal barriers. R-AMR demonstrated superior therapeutic effects compared to raw AMR. Bioinformatics and machine learning results indicate that Lipocalin 2 (LCN2) and Tissue inhibitor of metalloproteinase 1 (TIMP1) is a key target in UC, with the NOD-like receptor signaling pathway being one of its representative pathways. Molecular docking results reveal that Atractylenolide I (Atr I) has a strong affinity for LCN2 and is one of the active components enhancing the efficacy of R-AMR. In vitro experiments demonstrate that Atr I restores tight junctions between LPS-induced NCM460 cells. Targeted inhibition of LCN2 reduces NLRP3 inflammasome, Caspase 1 activation, and GSDMD-N expression, decreases proinflammatory factor release (IL-1β, IL-18, TNF-α, IL-6), and alleviates UC inflammatory responses. In vivo experiments verified that the therapeutic effect of AMR on UC is associated with the LCN2/NLRP3/ Caspase 1/GSDMD pyroptosis pathway. Both raw AMR and R-AMR exhibit protective effects against UC, with R-AMR displaying superior therapeutic outcomes. Its bioactive constituent Atr I attenuates pyroptosis through targeted inhibition of LCN2, leading to preservation of the intestinal epithelial mucosal barrier and subsequent amelioration of UC symptoms.
Zhang A, Wen R, Zheng H, Liu Z, Wang J, Xue J, Yu H, Li C
Noninvasive Assessment of Colitis Activity by Targeted Imaging of Neutrophil Elastase with [68Ga]Ga-POL6014. Molecular pharmaceutics | 2026-06-15
Effective management of IBD necessitates ongoing evaluation of disease activity. Molecular imaging of neutrophil elastase (NE) could address this urgent need as it mechanistically targets the early event of intestinal inflammation. In this study, based on macrocyclic peptide POL6014, [68Ga]Ga-POL6014 was developed for noninvasive assessment of colitis activity and treatment response through targeting of NE. [68Ga]Ga-POL6014 exhibited high specificity and affinity for NE with the KD of 14.81 nM and IC50 of 3.02 nM. In PET imaging, [68Ga]Ga-POL6014 could quickly visualize inflammation sites with colon uptake of 3.15 ± 0.63%ID/g and colon/muscle ratio of 4.92 ± 0.74 at 30 min p.i.. The specificity of [68Ga]Ga-POL6014 was demonstrated by the dose-response blocking studies with POL6014. Furthermore, [68Ga]Ga-POL6014 PET was used to evaluate treatment response to 5-ASA. The treatment significantly inhibited colon uptake of [68Ga]Ga-POL6014 (1.71 ± 0.21 %ID/g), accompanied by a decrease in imaging contrast (2.81 ± 0.26). Immunofluorescence revealed the preservation of mucosal barrier integrity and a remarkable decrease in NE positive cells after 5-ASA treatment. Moreover, there were good correlations between PET quantification with NE expression and DAI score, indicating the reliability of [68Ga]Ga-POL6014. Additionally, [68Ga]Ga-POL6014 was widely distributed and cleared rapidly from nonspecific organs and blood pool, and was excreted through urinary system, suggesting its favorable pharmacokinetics. In conclusion, [68Ga]Ga-POL6014 is a promising tracer that enables in vivo globally mapping of neutrophil-mediated inflammation in the entire gastrointestinal tract for early diagnosis, assessment of disease activity and evaluation of anti-inflammatory treatment response.
Wang X, Niu M, Guo Y, Wang J, Ou H, Xin K, Xing T, Ma T, Wang J, Ye J
TREM-1-dependent macrophage infiltration mediates visceral hypersensitivity via vlPAG GABAergic neuron activation in a mouse model of inflammatory bowel disease. Cellular & molecular biology letters | 2026-06-14
Visceral pain is a common symptom of inflammatory bowel disease (IBD). Although triggering receptor expressed on myeloid cells-1 (TREM-1) has been shown to induce infiltration of peripheral immune cells into the central nervous system, the specific contribution of peripheral monocytes/macrophages (Mo/MΦ) to visceral pain in IBD remains elusive. This study aimed to investigate the effect of TREM-1-dependent macrophage infiltration in the periaqueductal gray (PAG) on visceral pain and the underlying mechanisms in IBD. Male C57BL/6 J or Trem1-/- mice were fed 2% dextran sodium sulfate (DSS) for 7 days to induce colitis. Flow sorting, flow cytometry, and western blot were employed to isolate, transfer, and detect immune cells as well as TREM-1 expression. Immunofluorescence and in vitro brain slice electrophysiology were used to assess the activity of GABAergic neurons. Visceral pain was evaluated using the abdominal withdrawal reflex (AWR) score, visceral pain threshold, and electromyography (EMG). Peripheral Mo/MΦ infiltration into the PAG played a dominant role in enhancing ventrolateral PAG (vlPAG) GABAergic neuronal activity in mice with acute colitis, compared with the relatively minor contributions of resident microglia and peripheral neutrophils. This promoted acute visceral pain during intestinal inflammation with visceral pain persisting into the remission phase. To validate the role of peripheral TREM-1-expressing Mo/MΦ in visceral pain, microinjection of Ly6C⁺ monocytes into the vlPAG led to activation of vlPAG GABAergic neurons and an increase in visceral pain sensitivity. Pharmacological inhibition and gene knockout of TREM-1 both reduced Mo/MΦ infiltration, leading to decreased vlPAG GABAergic neuronal activity and mitigatory visceral pain. Our study identifies peripheral Mo/MΦ TREM-1 as a mediator promoting visceral pain via vlPAG GABAergic neuron activation. This finding presents a promising therapeutic approach for treating acute intestinal inflammation and visceral pain in colitis, while also offering a potential target for managing chronic visceral pain that persists in patients with IBD.
Zhou ZM, Song W, Guo MM, Chu YQ, Wang LB, Cheng P, Huang JW, Su T, Huang XF, Zhang YM
Epidemiology & Outcomes (7 papers)
Prevalence and Clinical Correlates of Avoidant/Restrictive Food Intake Disorder (ARFID) Among Patients with Inflammatory Bowel Disease: A Systematic Review.Review Journal of clinical psychology in medical settings | 2026-06-19
Avoidant/restrictive food intake disorder (ARFID) is an eating disorder characterized by inadequate or restricted food intake unrelated to body image or weight concerns. ARFID is frequently observed in patients with gastrointestinal disorders. Given the growing clinical interest, we conducted this systematic review to synthesize evidence, assessment approaches regarding ARFID-like symptomatology in adult patients with inflammatory bowel disease (IBD). A systematic search of MEDLINE, Scopus, Web of Science, PsycInfo was conducted in July 2025, yielding seven studies on ARFID in IBD. This review followed the framework outlined by Page (2021). Prevalence rates, assessment tools, associations with clinical, psychological factors were synthesized. Reported prevalence of ARFID-like behaviors ranged from 10.2 to 51.3%, reflecting differences in screening tools, cut-offs. Studies applying lower cut-offs (≥ 24) for the Nine Item ARFID Screen (NIAS) showed a weighted mean prevalence of 24, 2%, whereas stricter cut-offs (≥ 28) resulted in a a prevalence of 18, 6%, in line with the results from the Pica, ARFID, Rumination Disorder Interview-ARFID Questionnaire (PARDI-AR-Q). Higher ARFID levels were consistently linked to symptom-based clinical activity. Despite limited evidence, in some patients with normalized inflammatory markers, restrictive eating may persist, suggesting functional mechanisms beyond inflammation. Psychological distress, particularly anxiety, gastrointestinal-specific anxiety, was strongly associated with ARFID-like behaviors. The interplay between ARFID, symptom activity, psychological distress underscores the need for an integrated approach addressing gastroenterological, psychological, nutritional factors, aiming to improve ARFID screening, management in patients with IBD.
Caruso A, Latella G, Di Giacomo D, Galli F
GLP-1 receptor agonists and clinical outcomes in adults with Crohn’s disease and obesity: a propensity score-matched real-world cohort study. Scientific reports | 2026-06-19
Obesity affects 15%-40% of adults with Crohn’s disease (CD) and is associated with worse outcomes. GLP-1 receptor agonists (GLP-1RAs) have pleiotropic anti-inflammatory effects, yet their clinical impact in CD with comorbid obesity is incompletely characterized. We evaluated whether GLP-1RA initiation was associated with mortality, health care utilization, and TNF inhibitor use as a proxy measure of treatment intensity. Retrospective new-user cohort study using the TriNetX Global Collaborative Network (162 organizations, 2015-2024). Adults (≥ 18 years) with CD and obesity without prior GLP-1RA exposure were included. Nonusers received calendar-time-matched index dates to minimize immortal time bias. Propensity score matching (1:1) incorporated > 30 covariates including comorbidities, CD treatment intensity proxies, and inflammatory markers. Outcomes were assessed at 1 year (days 1-365 post-index) and 5 years (days 1-1,825 post-index); both time windows were analyzed as fixed horizons under an intention-to-treat framework using separate TriNetX query runs. Patients were censored at last recorded EHR encounter or study end (2024). Due to database constraints, detailed longitudinal exposure data (adherence, discontinuation, agent switching) were not available. Among 10,550 GLP-1RA users and 108,944 nonusers, 9,766 pairs were matched at 1 year and 9,320 at 5 years (the latter representing a subset of the base population with sufficient follow-up). After matching, covariates were well-balanced (all SMDs < 0.1 except BMI by design). At 1 year, GLP-1RA initiation was associated with lower mortality (0.7% vs. 4.2%; RR 0.17, 95% CI 0.13-0.22), hospitalization (10.0% vs. 24.7%; RR 0.40, 95% CI 0.38-0.43), ED visits (18.9% vs. 25.3%; RR 0.75, 95% CI 0.71-0.79), and TNF inhibitor use (7.1% vs. 10.9%; RR 0.65, 95% CI 0.60-0.72); corticosteroid rates were similar (RR 1.00, 95% CI 0.96-1.03). At 5 years, all utilization associations were sustained; corticosteroid use was modestly lower (RR 0.91, 95% CI 0.89-0.94). E-value for 1-year mortality upper CI: 8.56; healthy-user bias cannot be excluded. In adults with CD and obesity, GLP-1RA initiation was associated with lower health care utilization and lower TNF inhibitor use at 1 and 5 years; the latter should not be interpreted as evidence of reduced treatment escalation given inability to distinguish new initiation from continuation. The observed mortality difference is unlikely to reflect a true causal effect and should be treated as hypothesis-generating. These findings support GLP-1RA metabolic safety in this population and warrant prospective evaluation.
Ganju N, Ssebambulidde K, Gupta S, Adidam SR, Michael M, Kibreab A, Aduli F
Teclistamab for treatment-refractory autoimmune diseases: a multicentre case series. Annals of the rheumatic diseases | 2026-06-19
This study aimed to evaluate the safety and efficacy of teclistamab, a T cell-redirecting bispecific antibody targeting B-cell maturation antigen, in a case series of severe autoimmune diseases. Data were retrospectively collected from patients with treatment-refractory systemic sclerosis (SSc), idiopathic inflammatory myopathies (IIMs), systemic lupus erythematosus (SLE), undifferentiated connective tissue disease (UCTD), or IgG4-related disease (IgG4-RD) who received 1 cycle of teclistamab at 5 European centres. Eighteen patients (72% women, median age 48.5 years, 10 SSc, 4 IIM, 2 SLE, 1 UCTD, and 1 IgG4-RD) with a median of 5 prior therapies and a median cumulative dose of 6.36 mg/kg teclistamab were included. The median follow-up was 5.1 months (range, 0.8-21.2 months). A total of 22 cytokine release syndrome episodes (16 grade 1 and 6 grade 2) occurred in 12 patients (67%). All patients developed severe hypogammaglobulinaemia, and 5 (28%) experienced severe infections. Two patients developed an inflammatory bowel disease-like colitis. Two patients with severe SSc-associated cardiac involvement died, 1 due to sudden cardiac death and the other following diffuse alveolar haemorrhage and heart failure. B-cell depletion was observed in all patients, accompanied by significant reductions in autoantibody levels. Teclistamab was associated with major clinical responses in 11 (61%) and minimal-to-moderate responses in 4 (22%) patients, despite discontinuation of immunosuppressive therapy. Teclistamab demonstrated the potential to induce treatment-free responses in refractory autoimmune disease, but clinically relevant safety events, including infections and fatal outcomes in patients with advanced cardiac involvement, highlight the need for careful patient selection and monitoring.
Albach FN, Phithak E, Biesen R, Kleyer A, Siegert E, Minopoulou I, Algharably E, Casteleyn V, Beenken AE, Schneider U
Letter: Does the Association Between Mild Endoscopic Activity and Adverse Outcomes Justify Treatment Escalation in Older Adults With Inflammatory Bowel Disease?Letter★ Alimentary pharmacology & therapeutics | 2026-06-19
Transcatheter Aortic Valve Replacement Outcomes in Patients with Chronic Inflammatory Systemic Diseases. The American journal of cardiology | 2026-06-18
The clinical impact of performing transcatheter aortic valve replacement (TAVR) in patients with chronic inflammatory systemic diseases (CIDs) is not well reported. Hence, we designed this study to evaluate whether coexistence of CIDs in TAVR patients leads to worse clinical outcomes. We retrospectively studied TAVR patients at our institution between 11/21/2011 and 03/29/2024. Patients diagnosed with chronic inflammatory diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), scleroderma, Sjögren’s syndrome, inflammatory bowel disease, or other related diseases were identified using International Classification of Diseases codes. Clinical outcomes during inpatient and at one-year were compared between CIDs and no-CID patients. Our study included 2,880 TAVR patients with mean age of 79±9 years, 45% were female, and 78% were Caucasian. CIDs patients comprised 6.4% (n=185) of the total cohort. The CIDs cohort had a higher proportion of females (61.6 vs. 43.9%, p<0.001), immunosuppressive therapy (5.9 vs. 2.9%, p=0.02), NYHA class III or IV symptoms (51.9 vs. 40%, p=0.04), and higher STS score (4.1 vs. 3.4; p=0.04). In-hospital mortality (0.0 vs. 1.7%; p=0.08) was similar between the CIDs and no-CIDs groups; however, vascular complications (10.3% vs 6.1%, p=0.036) and unplanned vascular interventions (5.4 vs. 1.9%; p=0.003) were more common in CIDs patients. Survival analysis showed no difference in one-year mortality (8.9 vs. 8.91%, log-rank p=0.73) between the two groups. In conclusion, TAVR in CIDs patients is safe and has comparable immediate and one-year adverse outcomes compared to non-CIDs patients, however these patients are more prone to vascular access complications and may require more unplanned vascular interventions.
Verma BR, Sadeghpour A, Hani FB, Ahmed S, Waksman O, Sawant V, Rappaport H, Arguli AA, Galo J, Cellamare M
Inflammatory Bowel Disease Self-Management: An Underappreciated Means to Improve Patient Outcomes.Editorial Digestive diseases and sciences | 2026-06-17
Abstract not available.
Zhang X, Conley S, Kamp K
Medical and surgical therapies for patients with inflammatory bowel diseases and prior or coexisting cancer: a Danish nationwide cohort study.★ Journal of Crohn’s & colitis | 2026-06
As a result of an aging population and the rising incidence of inflammatory bowel diseases (IBD) across all age groups, more patients with IBD are being diagnosed with cancer both before and after their IBD diagnosis. We describe the treatment of patients with IBD with prior or coexisting cancer relative to patients with IBD and no cancer. Danish national registers were used to identify incident and prevalent patients with IBD, drug exposure, and cancer status, from 1996 to 2022. Cox regressions were used to compare medications and the risk of surgery among patients with and without cancer. In total 59 494 patients with IBD (20 551 Crohn’s disease [CD; 34.5%], 38 943 ulcerative colitis [UC; 65.5%]) were included. Of those, 2675 (4.5%) had been diagnosed with cancer prior to IBD. Of the remaining 56 819 patients with IBD, 6636 (11.7%) had their first cancer develop after their IBD diagnosis. Prior cancer was associated with reduced immunomodulator use for CD and UC, and increased anti-tumor necrosis factor (anti-TNF) use in UC. Furthermore, patients with CD and UC and a history of cancer had an increased risk of undergoing IBD-related surgery during follow-up. Patients who developed cancer during the course of their IBD largely had their anti-TNF and immunomodulator therapy discontinued following a cancer diagnosis. Patients with IBD and prior or coexisting cancer were treated differently from patients with no history of cancer. We observed greater caution around initiating immunosuppressants for patients with prior cancer, while more patients required IBD-related surgery. Greater caution was observed around reinitiating immunosuppressants for patients diagnosed with cancer.
Plovgaard J, Wewer MD, Bendtsen F, Burisch J
Genetics & Genomics (7 papers)
Combined acetaldehyde metabolism burden modifies IBD susceptibility to alcohol consumption.★ Gut | 2026-06-17
The effect of alcohol consumption on IBD remains inconclusive, potentially due to the overlooked role of alcohol metabolism. We aimed to investigate the potential modifying role of alcohol metabolic capacity in the associations. A prospective cohort study (n=455 417) was used for association analysis between alcohol consumption and IBD risk using Cox proportional hazards regression. An acetaldehyde burden score, using genetic variants of alcohol dehydrogenase and aldehyde dehydrogenase validated by expression quantitative trait loci and proteomic data, was constructed to test effect modification. Genetic and metabolomic analyses, along with mice and human-derived colonic organoid experiments, were conducted to strengthen causal inference. The inverse association between alcohol and IBD risk was mainly attributable to red wine. Among individuals with low burden, reflecting low acetaldehyde generation and high acetaldehyde metabolism, per SD increase in red wine consumption (equivalent to 59.4 g/week of pure alcohol intake) was associated with a 20% (95% CI 7% to 31%) reduced Crohn’s disease risk, whereas a 38% (95% CI 13% to 70%) increased risk among those with high burden. Genetic and metabolomic analyses further revealed harmful effects of acetaldehyde and protective effects of acetate. In vivo and in vitro experiments further confirmed these effects and showed that modulation of aldehyde dehydrogenase activity significantly altered colitis outcomes. Acetaldehyde metabolism burden modifies susceptibility to alcohol-related IBD and emphasises the importance of considering individual differences in alcohol metabolism when developing precision prevention strategies for IBD.
Chen J, Guo Y, Hu J, Ye S, Yao J, Yanai H, Jairath V, Peyrin-Biroulet L, Dan L, Li X
Faroese whole genomes provide insight into ancestry and recent selection. eLife | 2026-06-16
The Faroe Islands are home to descendants of a North Atlantic founder population with a unique history shaped by both migration and periods of relative isolation. Here, we investigate the genetic diversity, population structure, and demographic history of the islands by analyzing whole genome sequencing data from 40 participants in the Faroe Genome Project. This represents the first whole genome sequencing panel of this size from the Faroe Islands. We observed numerous putatively functional private alleles, including stop gain variants and high impact missense variants in the cohort. Faroese individuals had a higher proportion of their genomes contained in long runs of homozygosity than other European groups, including Finnish, suggesting a more recent or stronger bottleneck in the Faroese population. Signals of positive selection were identified at loci containing genes that play roles in vitamin D and dietary fat absorption and DNA repair, while increased diversity on lactase persistence haplotypes was observed. Fine-scale analysis of haplotype structure in present-day and ancient European genomes revealed genetic affinities with ancient Iron Age individuals from the North and West of Europe, providing evidence for potential contributions to the Faroese gene pool from Celtic and Viking populations as well as information about the temporal order in which these events happened. This study highlights the impact of evolutionary processes, such as ancient admixture, founder events, and positive selection, on the present-day genetic architecture of North Atlantic founder populations like the Faroe Islands. Our DNA contains a wealth of information about our ancestors. By examining the DNA of present-day populations, researchers can infer aspects of their history, including migration patterns, interactions with other groups, changes in population size, and adaptation to local environments. When a small group of “founders” settles a new location, they carry only a subset of the larger population’s genetic diversity. As a result, their descendants often exhibit reduced genetic diversity and elevated frequencies of certain genetic variants, some of which may influence health, disease, or adaptation. The Faroe Islands, a remote North Atlantic archipelago, were settled around the 9th century CE, primarily by people from Scandinavia and the British Isles. Today’s population of approximately 54,000 Faroese descends from this relatively small founding group. This distinctive demographic history – characterized by mixed ancestry, geographic isolation, and a limited number of founders – is likely reflected in the genomes of present-day Faroese individuals. To investigate the genetic diversity, ancestry, and evolutionary history of the Faroese population, Hamid et al. conducted whole-genome sequencing on 40 individuals selected to represent the geographic diversity of the islands. Previous studies of the Faroese population were limited either to small sample sizes (fewer than 10 individuals) or to specific regions of the genome, leaving substantial gaps in our understanding of the population’s full genetic landscape. The Faroe Islands also have elevated rates of several diseases, including inflammatory bowel disease and type 2 diabetes, compared with other European populations. Understanding the unique genetic architecture and demographic history of the Faroese population may therefore provide important insight into the genetic basis of these health disparities. The analyses revealed that Faroese individuals carry numerous rare and potentially disease-associated genetic variants that are absent from mainland European populations, including variants predicted to disrupt gene function. Compared with other European groups –including Finns, another well-known founder population – Faroese genomes contain longer runs of homozygosity (long, identical DNA segments), reflecting extensive segments of identical DNA inherited from common ancestors. This pattern suggests a stronger or more recent population bottleneck in the Faroese population. Hamid et al. also identified signatures of natural selection in genes involved in vitamin D metabolism and dietary fat absorption (SLC10A1), as well as DNA repair (POLQ), which may reflect adaptation to the Faroese environment and traditional diet. Comparisons with ancient European genomes indicated that the Faroese derive approximately equal ancestry from Iron Age “West European” (Celtic-related) and “North European” (Viking-related) populations. Importantly, the data suggest that this genetic mixing likely occurred before the settlement of the islands rather than afterwards. These findings have direct relevance for the Faroese population because they identify genetic variants enriched in the islands that may contribute to conditions such as glycogen storage disease, ankylosing spondylitis, and other disorders. In the future, this knowledge could help inform disease prevention strategies and clinical care in the Faroe Islands. However, the study of Hamid et al. represents only a pilot phase. A greater ongoing effort, the FarGen project, aims to integrate genomic data with detailed health records to better understand the relationship between genetics and disease in the Faroese population. More broadly, the Faroe Islands provide an important model for studying how historical isolation and founder effects shape genetic diversity and disease risk in human populations worldwide.
Hamid I, Mortensen Ó, Refoyo-Martínez A, Lydersen LN, Emde AK, Hendershott M, Apol KD, Andorsdóttir G, Meisner J, Wasik KA
Single-cell RNA sequencing of terminal ileal biopsies identifies signatures of Crohn’s disease pathogenesis. Nature genetics | 2026-06-15
Crohn’s disease (CD) is a chronic inflammatory bowel disease exhibiting substantial heterogeneity in clinical presentation and response to therapy. To explore its molecular basis, we developed IBDverse, a large single-cell RNA sequencing (scRNA-seq) dataset of terminal ileal biopsies, profiling over 1.1 million cells from 111 patients with CD and 232 healthy controls. This resource integrates discovery and replication cohorts for the robust identification of CD-associated cell types, genes and pathways. We uncovered epithelial changes marked by interferon-driven upregulation of major histocompatibility complex class I molecules that persisted in progenitor cells after macroscopic inflammation resolution. ITGA4+ macrophages were identified as key inflammatory drivers, showing enriched JAK-STAT signaling and cytokine expression (interleukin-6 (IL-6), IL-12 and IL-23). Heritability analysis linked inflammatory monocytes and macrophages to CD susceptibility, implicating resident and recruited immune cells in pathogenesis. These findings establish a comprehensive cellular and molecular framework for CD, offering insights into disease mechanisms and therapeutic opportunities.
Krzak M, Alegbe T, Taylor DL, Jones GR, Ghouraba M, Strickland M, Harris BT, Satti R, Arestang K, Ramirez-Navarro L
Cross-trait mapping of shared susceptibility across inflammatory bowel disease and spondyloarthropathies. Journal of translational medicine | 2026-06-13
Inflammatory bowel diseases (IBDs) and spondyloarthropathies (SpAs) frequently co-occur, yet the subtype-specific genetic architecture and effector tissues that implement this gut-joint coupling remain poorly defined. We integrated European-ancestry GWAS summary statistics for IBD, Crohn’s disease, ulcerative colitis, ankylosing spondylitis, psoriatic arthritis, reactive arthritis and enteropathic arthritis, covering 22.21 million variants across 1,263,767 individuals. We quantified genome-wide and local sharing (S-LDSC/LDSC, ρ-HESS), identified pleiotropic loci (MTAG, CPASSOC) in trait pairs with significant genome-wide genetic correlation, and prioritized shared loci by integrating local-correlation evidence with GWAS-PW and GCTA-COJO, mapped signals to tissues/cell types (LDSC-SEG, gsMap), prioritized effector genes (UTMOST, FUSION, SMR, immune-cell scPrediXcan), and assessed directionality using bidirectional Mendelian randomization. IBD showed 16.4% liability-scale SNP heritability (CD 21.5%; UC 15.2%), whereas SpA subtype heritability ranged from 2.4% (ReA) to 62.9% (AS). Genetic correlations were positive but heterogeneous, with the strongest sharing observed for EnA-related pairs. Local genetic analyses indicated structured but uneven regional sharing across subtype pairs, with the most robust local support concentrated in PsA- and EnA-related comparisons. Tissue and cell-type analyses converged mainly on immune- and barrier-related contexts, including blood, synovial fluid, spleen, lung, and lymphoid tissues, as well as T-lineage and myeloid immune compartments. Complementary gsMap projection suggested a developmentally informed gut-immune spatial scaffold rather than a uniform anatomical pattern. Pair-specific transcriptomic integration further prioritized recurrent candidate effectors across the IBD-SpA axis, while bidirectional Mendelian randomization supported a predominantly forward component from intestinal inflammatory liability to selected SpA phenotypes. These results provide a multi-layer genetic and biological framework for gut-joint comorbidity, implicating shared immune and barrier niches and supporting a gut-first component in the IBD-SpA axis.
Wang L, Li F, Wang J, Wang H, Gong L, Wang Y
Glycoproteomic and genetic analysis of N-glycosylation of complement component C3 reveals immune pathway regulation. Genome biology | 2026-06-12
Post-translational modifications represent a critical layer of protein regulation, yet their genetic control and population variation remain poorly characterized. Here we present a comprehensive analysis integrating population-scale glycoproteomics with genome-wide association study (GWAS) to uncover genetic regulatory networks controlling N-glycosylation of complement component C3. Through LC-MS glycopeptide analysis of 816 Croatian adults, we characterize site-specific N-glycosylation at two C3 sites (N63 and N917), confirming an unusual phenotype consisting of exclusive high-mannose structures rather than complex glycans typical of secreted proteins. GWAS identifies six genetic loci significantly associated with C3 N-glycosylation patterns, including genes encoding proteins involved in maintenance of the protein secretory pathway, proteins involved in the complement pathway or regulation of complement, and regulators of gene expression. Using colocalization analysis, we discover shared causal variants between C3 glycosylation and immune diseases, particularly rheumatoid arthritis and inflammatory bowel disease, suggesting glycosylation as a mechanistic link between genetic variation and disease susceptibility. C3 N-glycoprofiling reveals significant associations with sex, age, and metabolic parameters, indicating integration of genetic and environmental factors. Structural modeling provides mechanistic insights, revealing how protein architecture constrains glycan processing and enables functional glycan-mediated interactions. Our multiomic approach establishes a framework for understanding how genetic variation shapes post-translational modifications at population scale, demonstrating C3 N-glycosylation as both a genetically and environmentally regulated checkpoint in complement activation with implications for precision medicine approaches in immune and metabolic diseases.
Šoić D, Rudman N, Grant OC, Vučković F, Frkatović-Hodžić A, Gazaway E, Pociot F, Wilson JF, Polašek O, Woods RJ
Multi-Cohort Transcriptomics Combined with Mendelian Randomization Identifies PPARGC1A, NAAA and GIPC2 as NLRP3 Inflammasome-Related Key Genes in Ulcerative Colitis. Journal of inflammation research | 2026-06-10
Ulcerative Colitis (UC), a subtype of inflammatory bowel disease with unclear specific pathogenesis, was associated with recurrent inflammatory infections, genetics, and immunodeficiency. This study aimed to analyze the potential pathogenesis of NLRP3 inflammasome (NLRP3-INF)-mediated UC via transcriptomics combined with Mendelian Randomization (MR), explore the causal relationship between NLRP3-INF, related target genes and UC, and provide insights for mining UC therapeutic targets. Gene expression data (GSE87473 as training set, GSE75214 as validation set, GSE87466 as external validation set) were obtained. Differential expression analysis and Weighted Gene Co-expression Network Analysis (WGCNA) were performed to screen differentially expressed genes (DEGs) and NLRP3-INF related genes (NLRP3-RGs) related module genes. Candidate genes were obtained by intersecting DEGs with module genes. MR analysis was conducted between candidate genes and UC. Receiver Operating Characteristic (ROC) analysis and expression validation were used to confirm key genes; immune infiltration drug prediction; and molecular dynamics (MD) simulation analyses were carried out, and the expression of key genes was further verified in the UC mouse model. A total of 942 DEGs were screened. WGCNA identified eight modules, with the MEyellow module (813 genes) highly correlated with NLRP3-RGs. A total of 307 candidate genes were obtained. Nine candidate key genes were screened through MR analysis; after validation, PPARGC1A (Peroxisome proliferator-activated receptor gamma coactivator 1-alpha), NAAA (N-acylethanolamine acid amidase), and GIPC2 (GIPC PDZ domain containing family member 2) (significantly downregulated in UC) were confirmed as key genes. They were correlated immune cells such as M0 macrophages and activated CD4+ T cells; Molecular docking revealed a binding free energy of -8.7 kcal/mol between PPARGC1A and Rosiglitazone, indicating favorable binding affinity. Molecular dynamics simulations confirmed the binding conformation remained stable over 100 ns Animal experiments confirmed lower expression of the three key genes in the model group. PPARGC1A, NAAA, and GIPC2 were identified through bioinformatics analyses as key genes for NLRP3-INF-mediated UC, which could serve as potential biomarkers and provide a basis for UC pathogenesis research and therapeutic target development.
Cheng J, Huang Y
Crohn’s Disease Enteritis: Pathophysiological Mechanisms and Therapeutic Approaches.Review Scandinavian journal of immunology | 2026-06
Crohn’s disease (CD) is a chronic, relapsing-remitting inflammatory condition of the gastrointestinal tract. This review provides a comprehensive analysis of the underlying pathophysiological mechanisms, highlighting the interplay between intestinal epithelial cells, dysregulated immune responses, gut microbiota and environmental triggers in CD. Key genetic susceptibilities (e.g., NOD2, ATG16L1, IL23R) and dysregulated T-cell signalling, particularly involving T-helper 1 (Th1) and T-helper 17 (Th17) pathways, are central to CD pathogenesis. The progression of the disease is driven by complex cytokine and chemokine networks (e.g., TNF-α, IL-6, IL-17), epithelial barrier dysfunction and microbial dysbiosis, all of which contribute to chronic inflammation and mucosal damage. Advanced models, including organoids and patient-derived xenografts, have elucidated these mechanisms, aiding in biomarker discovery and drug development. Diagnostic advancements such as capsule endoscopy, magnetic resonance enterography, faecal calprotectin and molecular assays enable precise characterization of CD phenotypes and activity. Therapeutic strategies now encompass targeted biologics that neutralize key cytokines, small-molecule Janus kinase (JAK) inhibitors that interrupt intracellular inflammatory signalling and emerging modalities targeting epithelial repair and microbiome restoration. Despite significant progress, challenges persist in managing refractory CD, including loss of response to biologics and fibrostenotic or fistulizing complications. Personalized approaches based on immunological profiling, microbiota composition and molecular diagnostics hold promise for more effective interventions. This review underscores the complexity of intestinal inflammation in CD and advocates for integrated, personalized strategies to improve patient outcomes.
Jia L, Wang H
IBD-associated Neoplasia (7 papers)
Exploring associations between epidemiological risk factors and colorectal cancer in Oman: a case-control study. BMJ open | 2026-06-19
To identify risk factors and examine associations between colorectal cancer (CRC) status and modifiable and non-modifiable risk factors among patients diagnosed in Oman, considering the existence and increase of incidence and prevalence of these risk factors. A multicentre case-control study. Sultan Qaboos University Hospital and the Royal Hospital in Muscat, Oman. Patients diagnosed with CRC (n=166) and controls (n=166). A questionnaire adapted from the Colon Cancer Family Registry and other previously published studies was used to collect data on sociodemographic characteristics, modifiable and non-modifiable CRC risk factors and coexisting morbidities. Univariable and multivariable logistic regression analyses were performed to examine associations between CRC status and independent variables. Multivariable analysis demonstrated significant associations between CRC status and several risk factors. Smoking was associated with a fourfold increased risk of CRC (adjusted OR (aOR): 4.35, 95% CI 2.26 to 8.36). Higher body mass index was also associated with increased CRC risk (aOR: 2.42, 95% CI 1.23 to 4.76), while individuals with a family history of CRC, including first-degree relatives (biological parents, siblings and children) and second-degree relatives (grandparents, uncles and aunts) had more than double the risk (aOR: 2.10, 95% CI 1.15 to 3.82). Also, polyps had double the risk (aOR 2.61, 95% CI 1.40 to 4.84) In addition, CRC was more common among patients with diabetes (aOR 2.70, 95% CI 1.52 to 4.80), hypertension (aOR 4.13, 95% CI 2.03 to 8.42) and inflammatory bowel disease (aOR 3.48, 95% CI 1.13 to 10.67). Considering the existence of non-modifiable risk factors and the increase in incidence and prevalence of modifiable risk factors of CRC in Oman, the findings of this study underscore the need for targeted awareness initiatives, risk-based screening and early surveillance, particularly among high-risk groups. The results also support integrating smoking cessation, weight management and optimal control of chronic diseases into national CRC prevention programmes to reduce the overall CRC disease burden.
Rehman S, Shalaby A, Al-Busafi SA, Chan MF, Khabouri SA, Al Hinai M, Al Zaabi A, Al Masqari M, Qureshi A, Al Sumri H
An epithelial mesenchymal transition associated gene signature stratifies risk of ulcerative colitis associated colorectal cancer. Discover oncology | 2026-06-19
Patients with long-standing ulcerative colitis (UC) are at increased risk of developing colitis-associated colorectal cancer (UC-CRC). However, the molecular transition from chronic inflammation to neoplasia remains incompletely defined, and biomarkers for high-risk disease are still lacking. Transcriptomic datasets from UC and CRC cohorts were analyzed independently to identify reproducible transcriptional alterations. Differential expression and pathway enrichment analyses were followed by stepwise prioritization of candidate genes based on expression in UC-associated neoplasia, prognostic relevance in CRC, and classification performance. Receiver operating characteristic analysis and composite z-score modeling were used to evaluate signature performance, whereas gene co-expression analysis and single-sample gene set enrichment analysis were used to examine its biological context. Epithelial-mesenchymal transition (EMT) emerged as a consistently enriched pathway among upregulated genes in UC and CRC. Intersection of EMT-associated genes identified 24 shared candidates, of which 14 were significantly upregulated in UC-associated neoplasia compared with quiescent UC and showed consistent upregulation across independent active UC datasets. These genes showed strong discriminatory performance (AUC > 0.85), and Random Forest analysis further refined a seven-gene panel (FAP, TIMP1, COL12A1, CALU, INHBA, SPP1, and CTHRC1). A composite z-score derived from this panel distinguished neoplastic from quiescent UC and showed a stepwise increase across disease states. Functional analyses linked the signature to EMT, hypoxia, angiogenesis, coagulation, and inflammatory signaling. This study identified a seven-gene EMT-associated signature linked to UC-associated neoplastic transformation. The signature may support molecular risk stratification in UC and provides a framework for future validation in surveillance settings.
Belder N
Brominated Flame Retardants: UQCRC1 and NR3C2 as Potential Targets in IBD and CRC. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association | 2026-06-18
Brominated flame retardants (BFRs) are persistent pollutants with health concerns, yet their molecular mechanisms in the inflammatory bowel disease (IBD) and colorectal cancer (CRC) are unclear. We employed an integrated approach combining computational toxicology, bioinformatics, and molecular docking to identify core molecular targets linking BFR exposure to IBD/CRC. The prognostic and immunological significance of key genes was validated using TCGA data and functional assays in human CRC (HT29) and normal colon epithelial (NCM460) cells. We identified 12 core targets, notably UQCRC1 and NR3C2, which stably bind BFRs. Low expression of UQCRC1 and NR3C2 predicted poor patient prognosis and exhibited consistent positive correlations with anti-tumor immune cell infiltration. In vitro experiments demonstrated that BFR (TBBPA and HBCD) exposure markedly promoted the proliferation, viability and cell cycle progression of HT29 CRC cells, accompanied by significant downregulation of UQCRC1 and NR3C2 expression. In normal NCM460 colon epithelial cells, BFR treatment induced cytotoxicity, inhibited cell proliferation, triggered the upregulation of pro-inflammatory cytokines, and disrupted intestinal barrier function by suppressing the expression of intestinal tight junction proteins. BFR exposure was accompanied by altered expression of UQCRC1/NR3C2 and phenotypic changes in colon cells. Dysregulation of the two genes was significantly correlated with clinical prognosis and tumor immune microenvironment in IBD and CRC patients.
Wu J, Li H, Wu C, Wu Y, Yu H, Chen Z
Regulatory mechanism of the RNF168-SCCA1-MYH9 signaling axis in the response of ulcerative colitis. Journal of gastroenterology | 2026-06-17
The potential function of E3 ubiquitin ligase RNF168 in inflammatory processes remains largely unexplored. Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) characterized by chronic inflammation and epithelial damage of the intestinal mucosa. The pathophysiology of UC is complex, and its mechanisms remain incompletely understood. This study explores the role of RNF168 in the pathogenesis of experimental colitis. RNF168-knockout murine models were employed. The functional impact of RNF168 was determined by assessing colitis severity and susceptibility in these mice through a comprehensive evaluation of disease activity index, histological scoring, and pro-inflammatory cytokine levels. The molecular mechanism was explained using co-immunoprecipitation combined with mass spectrometry to identify and confirm downstream effectors. We identified RNF168 as a susceptibility gene for colonic inflammation in mouse models and cell lines. RNF168 downregulation in colonic inflammation reduces SCCA1 ubiquitination, leading to SCCA1 accumulation. Increased SCCA1 contribute to inflammation by suppresses the MYH9-p53 signaling pathway, subsequently reduces the expression of p53 and phosphorylated p53 (p-p53), thereby exacerbating the inflammatory response. Administration of the small-molecule SCCA1 inhibitor 1-PPA alleviated colonic inflammation pathology. Our findings reveal a novel ubiquitination-dependent pathway and identify SCCA1 as a promising therapeutic target for colonic inflammation. Our findings reveal a novel ubiquitination-dependent pathway in experimental colitis pathogenesis and identify SCCA1 as a promising therapeutic target for colitis. Elucidating these mechanisms opens avenues for developing therapies targeting inflammatory responses in UC.
Zhang X, Zhu J, Wei F, Bu L, Xing Y
Identification of Immune-Related Genes in Predicting the Progression of Colitis-Associated Colorectal Cancer: An Integrated Bioinformatics and Experimental Validation Study. Journal of inflammation research | 2026-06-11
Immune infiltration plays an important role in the pathogenesis of both ulcerative colitis (UC) and colorectal cancer (CRC). Our aim is to explore the significance of immune cell-related genes in colitis-associated colorectal cancer (CAC). Datasets related to UC and CRC were sourced from public databases. Key immune cell-related CAC genes (IC-CACs) were obtained by using WGCNA, differential expression and elastic net logistic regression analyses. Their diagnostic performance was assessed via ROC curves. Single-cell RNA sequencing (scRNA-seq) data were analyzed using the AUCell algorithm. Prognostic signatures were developed from differentially expressed genes between AUCell score-high and -low groups using Cox and LASSO regression. Moreover, the expressions of IC-CACGs were examined by RT-qPCR using clinical samples. We obtained 13 key IC-CACGs correlated with neutrophils and dendritic cells. ROC curves revealed that key IC-CACGs had the good ability to distinguish UC or CRC patients from controls. scRNA-seq analysis revealed enrichment of interferon response, inflammation, and PI3K-Akt-mTOR signaling in AUCell scorehigh groups, while glycolysis and EMT were enriched in scorelow groups. A 20-gene prognostic signature was constructed and validated, with low-risk patients showing better overall survival. Key IC-CACGs correlated strongly with prognostic genes, and high-risk patients exhibited higher TIDE scores, suggesting poorer immunotherapy response. CD69, CXCR4, and SAMSN1 were highly expressed in T cells and natural killer T cells, and their expressions were significantly increased in CAC samples. Our results provide the evidence for the promising role of immune cell-related genes in the development of CAC and new ideas for CAC prevention and treatment.
Chi C, Liu C, Wang B, Han W, Zhang Y, Chen J, Gao S
Chimeric antigen receptor technology: an emerging translational immunotherapy in nonneoplastic diseases.Review Frontiers in immunology | 2026-06-03
One of the most significant recent advancements in cancer immunotherapy is the development of chimeric antigen receptor (CAR) technology. More recently, this approach has been gradually modified for the research associated with various treatment-resistant nonneoplastic diseases by engineering immune cells to provide precise targeting. This narrative review discusses two primary therapeutic approaches the use of CAR technology in the treatment of nonneoplastic diseases. One strategy involves the elimination of specific pathogenic cell populations. Specifically, by engineering T cells, macrophages, or natural killer (NK) cells, pathogenic cells can be eliminated in autoimmune disorders, infectious diseases, and fibrotic lesions. The second approach aims to restore immune homeostasis by using engineered regulatory T cells (Tregs) to control augmented immune effector responses. This strategy has been shown to promote transplant tolerance and has therapeutic potential for inflammatory bowel disease and type 1 diabetes. Furthermore, this review addresses major issues concerning the persistence, safety, and manufacturing accessibility of CAR cells and discusses some emerging technological approaches that could be used for focused refinements of this technology. The precision medicine platform for CAR technology has advanced beyond oncology by integrating targeted cell destruction with the management of immune homeostasis. As future possibilities with frontier cell engineering and interdisciplinary approaches are explored, CAR cell therapy is likely to evolve into a more adaptable, refined, and clinically viable immunotherapy technology, with its therapeutic potential expanded to a broad range of diseases.
Zhou S, Li Y, Zhao J, Zhan W, Zhou C, Zou Y, Li X, Cui J, Wu J, Xia J
The Aging Microenvironment Shapes Angiogenic Remodeling in IBD-Associated Colorectal Carcinogenesis.Review★ Aging cell | 2026-06
Chronic intestinal inflammation establishes a pro-senescent microenvironment that fuels the stepwise evolution from inflammatory bowel disease (IBD) to colorectal cancer. Although cellular senescence initially functions as a tumor-suppressive barrier, the persistent accumulation of senescent cells can promote disease progression through the senescence-associated secretory phenotype (SASP). Key SASP mediators, including VEGF, IL-8/CXCL8, and matrix metalloproteinases (MMPs), reprogram endothelial and stromal compartments, driving aberrant neovascularization, vascular leakiness, extracellular-matrix remodeling, and tissue hypoxia that further reinforce inflammation and genomic instability. Emerging evidence also highlights marked heterogeneity among senescent epithelial, stromal, endothelial, and immune-cell populations within the inflamed intestinal mucosa, suggesting that distinct senescent subsets may differentially shape angiogenesis and malignant transformation. This review synthesizes current evidence linking inflammation-induced senescence to vascular dysfunction and the transition from IBD to colitis-associated colorectal cancer, and discusses therapeutic opportunities targeting the senescence-angiogenesis axis. By clarifying how the aging microenvironment reshapes intestinal angiogenesis, we propose a mechanistic framework for early intervention and cancer prevention in colitis-associated neoplasia.
Duan R, Chen Q, Xu Y, Yan Y, Jiang S
Nutrition & Lifestyle (7 papers)
Unique causes of exocrine pancreatic insufficiency: When to consider pancreatic enzyme supplementation: A narrative review.Review Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition | 2026-06-19
Exocrine pancreatic insufficiency (EPI) is a clinically significant disorder characterized by inadequate secretion or activity of pancreatic digestive enzymes, leading to maldigestion, malabsorption, and adverse nutritional and metabolic consequences. The causes of EPI can be divided into loss of pancreatic parenchyma, inhibition or inactivation of pancreatic secretion, and postcibal pancreatic asynchrony. Although most associated with intrinsic pancreatic diseases such as cystic fibrosis, chronic pancreatitis or pancreatic cancer, EPI is increasingly recognized in a range of other conditions including diabetes, inflammatory bowel disease, celiac disease, hypersecretory states, gastrointestinal surgeries, small intestinal bacterial overgrowth, drug side effects and aging. This narrative review summarizes the diagnosis and treatment of EPI along with a focused review of the pathophysiology, clinical consequences, diagnostic approaches, and treatment principles of EPI for a variety of conditions.
Williams V, Funk S
Beyond Inflammation - A Multidisciplinary Approach to Managing Obesity and Cardiometabolic Risk in Inflammatory Bowel Disease.Review Current diabetes reports | 2026-06-18
Adults with inflammatory bowel disease (IBD) demonstrate a high prevalence of obesity, metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiometabolic comorbidities. Cardiovascular disease (CVD) is a leading cause of mortality in IBD. This review examines cardiometabolic and obesity screening, and management within IBD models of care to optimise chronic disease management. Obesity prevalence in IBD has increased to 40%. Chronic systemic inflammation driven by visceral adiposity, proinflammatory cytokine production, insulin resistance and vascular endothelial dysfunction represent a unifying mechanism linking IBD, MASLD and CVD. Proactive management of cardiometabolic risk is not prioritised within traditional IBD service models. Therapeutic approaches to manage obesity and lower CVD risk in this cohort with concurrent optimisation of IBD control include dietary and lifestyle intervention through to anti-obesity pharmacotherapy and bariatric procedures. Integrated multidisciplinary models of care that leverage existing infrastructure and shared-care partnerships with primary care, proactive risk identification and management strategies should be adopted within specialist IBD services. As obesity, MASLD and CVD emerge as major contributors of morbidity and mortality in IBD, failure to systematically address cardiometabolic risk represents a critical gap in contemporary IBD care. Embedding proactive screening and multidisciplinary management within existing IBD infrastructure offers immediate actionable opportunity to improve long-term outcomes beyond inflammatory control.
Plush SL, Litwin P, Han S, Bryant RV, Kumar S, Kaazan P, Day AS
Ultra-processed food intake and risk of inflammatory bowel disease in the adult population ‒ A systematic review and meta-analysis. Revista espanola de enfermedades digestivas | 2026-06-18
The incidence of inflammatory bowel disease has risen in recent years. Although its pathophysiology remains unclear, evidence suggests that dietary factors, especially ultra-processed foods, may play a role. A systematic review was performed according to PRISMA guidelines. MEDLINE, SCOPUS and EMBASE were searched systematically from 2019 to 2025. Quality assessment was performed using the Newcastle-Ottawa score. This review aims to evaluate the association between ultra-processed food consumption and the development of inflammatory bowel disease among adults, by summarizing methodological features and key findings of prospective cohort studies and comparing inflammatory bowel disease risk between high and low ultra-processed food dietary patterns. A dichotomous meta-analysis was performed for overall inflammatory bowel disease, Crohn’s disease and ulcerative colitis. Pooled effect analysis was conducted using a random-effects model. Dichotomous variables were pooled as odds ratios. 7 studies were included in the systematic review, comprising 1,534,155 participants without inflammatory bowel disease. The median Newcastle-Ottawa was 7 [range 6-8]. A high intake of ultra-processed food was significantly associated with an increased risk of Crohn´s disease (OR 1.985, 95 % confidence Interval [CI]: 1.230-3.204; p = 0.005] and overall inflammatory bowel disease (OR 1.495, 95 % CI: 1.028-2.174; p = 0.035), but not in the case of UC (OR 1.324; 95 % CI: 0.893 - 1.962; p = 0.163) Conclusion: Ultra-processed food consumption appears to be associated with an increased risk of IBD, with a more consistent association observed for Crohn’s disease, which may partly explain the overall association observed for IBD, while no significant association was found for ulcerative colitis.
Mendoza-Rodríguez R, Gutiérrez-Garrido Á, Jiménez-Rosales R, Valverde-López F, Fernández-García R, Redondo-Cerezo E
Tasty&Healthy exclusive whole food diet in asymptomatic children and young adults with biologically active Crohn’s disease: the TASTI-E randomized controlled trial.★ Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association | 2026-06-17
Tasty&Healthy is an exclusive whole food diet designed to reduce inflammation in Crohn’s disease (CD) without the need for formula. This TASTI-E randomized-controlled trial compared the effect of Tasty&Healthy versus habitual diet on subclinical inflammation in CD (NCT#04239248). Clinically quiescent patients with CD, 6-40 years of age, with Mucosal Inflammation Non-invasive (MINI) index >8 reflecting bowel inflammation, were randomized to an 8-week Tasty&Healthy intervention or to continue their regular diet. Thereafter, the habitual group was offered an 8-week open-label Tasty&Healthy intervention. The primary outcome was >50% decline in calprotectin. The study was terminated early due to COVID-19-related challenges. Of the 46 randomized patients (mean age, 18.2±7.6 years; median disease duration, 9.01 months [IQR 2.9-17.1]), 19 were allocated to Tasty&Healthy and 27 to habitual diet. Calprotectin response was greater in the Tasty&Healthy (53%) versus habitual arm (7%, relative risk=3.23 [95%CI 1.15-9.01], p=0.028). Among 15 patients who crossed-over to Tasty&Healthy, the rates of calprotectin<250 μg/g (53% vs. 7%, respectively, p=0.045) and MINI <8 (93% versus 20%, p=0.002) were higher at week 16 versus week 8. Adherence to Tasty&Healthy was 77% based on self-reported questionnaires and 71% by fecal gluten. Micronutrient and macronutrient consumption was similar between the groups, except for higher fiber intake with Tasty&Healthy. The Tasty&Healthy intervention resulted in a unique serum metabolic signature. The Tasty&Healthy diet may reduce calprotectin levels in patients with CD with subclinical inflammation. Its flexible structure, free of formula, likely explains the high adherence among asymptomatic individuals.
Plotkin L, Aharoni-Frutkoff Y, Pollak D, Azulay A, Shavit Z, Focht G, Livovsky J, Lev-Tzion R, Koslowsky B, Boneh RS
Update on Diet and Nutritional Therapies in Patients with Inflammatory Bowel Disease.Review Digestive diseases and sciences | 2026-06-17
While the exact cause of inflammatory bowel disease (IBD) remains unclear, interactions among several complex mechanisms are thought to contribute to its pathogenesis. One such factor is diet, which has recently been investigated for its role in both IBD pathogenesis and treatment. This review examines the evidence regarding diet, nutrition support, and dietary supplements for managing IBD. The diets discussed include low fiber/residue, Crohn’s Disease exclusion, Specific Carbohydrate, Mediterranean, Anti-Inflammatory, Autoimmune Protocol, low FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols), lactose-free, and gluten-free diets. Nutrition support options include enteral nutrition, partial enteral nutrition, and parenteral nutrition. These modalities can be considered in specific situations, such as perioperative nutrition, protein-calorie malnutrition, and induction of remission. Dietary supplements studied for managing IBD include prebiotics, probiotics, vitamin D, omega-3 fatty acids, polyphenols, and aloe vera, which may be beneficial in managing IBD. Some challenges to consider in the dietary management of IBD include food avoidance, food insecurity, and cultural practices. When contemplating initiating one of these options, input from a multidisciplinary gastroenterology team should be considered.
Baniqued MR, Shah ND, Dominguez J, Parian AM
C3 glomerulopathy associated with anti-factor H autoantibodies in a child with inflammatory bowel disease. Pediatric nephrology (Berlin, Germany) | 2026-06-16
Complement dysregulation may occur secondary to systemic immune activation, but its relationship with inflammatory bowel disease (IBD) remains poorly defined. We report a 10-year-old boy presenting with severe anemia and newly diagnosed IBD who developed acute kidney injury with microscopic hematuria and proteinuria. Complement studies showed markedly reduced C3 and CH50 with normal C4. Kidney biopsy demonstrated diffuse proliferative glomerulonephritis with dominant C3 deposition and subendothelial immune complexes, consistent with C3 glomerulopathy. Additional complement testing revealed factor H depletion, high titers of anti-factor H autoantibodies, and elevated soluble C5b-9, while C3 nephritic factor and genetic testing of complement genes were negative. Multiple systemic autoantibodies were simultaneously present. Treatment with glucocorticoids resulted in rapid clinical improvement with normalization of kidney function, complement parameters, and disappearance of anti-factor H antibodies during follow-up. This case illustrates how transient systemic immune activation associated with intestinal inflammation may induce acquired complement dysregulation and trigger C3 glomerulopathy.
Ban M, Matković H, Aničić MN, Ćorić M, Prohászka Z, Lamot L
Crosstalk between circRNAs and the classic signaling pathways in IBD.Review RNA biology | 2026-06-15
Inflammatory bowel disease (IBD), which includes Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disorder of the gastrointestinal tract with a complex aetiology involving genetic, environmental (such as diet/lifestyle), and microbiota factors. The exact pathogenesis of IBD remains unclear, and current therapies show limited effectiveness. Circular RNAs (circRNAs) are a novel class of noncoding RNAs that have been implicated in the regulation of various biological processes. Many circRNAs show specific expression profiles in IBD patients and play important roles in IBD pathogenesis through different signalling pathways, such as the Janus kinase/signal transducer and activator of transcription (JAK/STAT) and nuclear factor-κB (NF-κB) pathways. Although research on circRNAs in IBD is still in its early stages, many circRNAs have emerged as potential diagnostic, prognostic biomarkers, and therapeutic targets for IBD. Here, we summarize the molecular functions and underlying mechanisms of circRNAs in IBD and discuss current challenges and future perspectives for clinical applications.
Jie M, Liao Q, Liu C
Extraintestinal Manifestations (6 papers)
Aberrant p53 overexpression in benign colon biopsies may predict dysplasia risk in patients with primary sclerosing cholangitis and inflammatory bowel disease. Histopathology | 2026-06-19
Patients with primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD), collectively termed PSC-IBD, have an increased risk of developing nonconventional and/or invisible colorectal dysplasia, particularly in the right/proximal colon, compared with patients with IBD alone. PSC-IBD patients are also more likely to exhibit abnormal DNA content (e.g. aneuploidy or an elevated 4N fraction) in the right/proximal colon, often preceding the detection of dysplasia. We therefore hypothesized that PSC-IBD patients who subsequently develop colorectal dysplasia may frequently demonstrate aberrant p53 immunohistochemical staining in histologically benign colon biopsies, particularly from the right/proximal colon, obtained prior to dysplasia detection. p53 immunohistochemistry was performed on 91 benign colon biopsies from 25 PSC-IBD patients obtained during the surveillance colonoscopy immediately preceding the procedure at which dysplasia was detected (mean interval: 20 months) (dysplasia group). As controls, p53 staining was performed on 76 benign colon biopsies from 20 IBD patients (10 PSC-IBD and 10 IBD-only) without a history of colorectal neoplasia. Nuclear staining intensity was graded as weak (1+), moderate (2+) or strong (3+), and staining extent was categorized as negative (<10%), patchy (10%-50%) or diffuse (>50%). Aberrant p53 overexpression was defined as strong nuclear staining in ≥10% of epithelial cells (patchy or diffuse). These results were compared with previously reported DNA flow cytometric findings from the same samples. Aberrant p53 overexpression was significantly more frequent in the dysplasia group than in controls (20% vs. 3% per biopsy, P < 0.001; 36% vs. 5% per patient, P = 0.027). Conversely, weak p53 staining was more common in controls (79% vs. 44% per biopsy, P < 0.001; 65% vs. 28% per patient, P = 0.013). Concordance between abnormal DNA content and aberrant p53 overexpression was 19% at the biopsy level and 42% at the patient level. Both aberrant p53 overexpression (72%) and abnormal DNA content (67%) were more frequently localized to the right/proximal colon. For predicting subsequent dysplasia, aberrant p53 overexpression demonstrated a sensitivity of 36%, specificity of 95%, positive predictive value (PPV) of 90% and negative predictive value (NPV) of 54%. Abnormal DNA content showed a sensitivity of 48%, specificity of 95%, PPV of 92% and NPV of 59%. When both markers were used together, sensitivity increased to 64%, with a specificity of 90%, PPV of 89% and NPV of 67%. PSC-IBD patients who subsequently develop colorectal dysplasia exhibit a significantly higher frequency of aberrant p53 overexpression in benign colon biopsies, particularly from the right/proximal colon, obtained prior to dysplasia detection compared with IBD patients who do not develop dysplasia. These findings suggest that aberrant p53 overexpression in benign colon biopsies may help identify PSC-IBD patients at increased risk for colorectal dysplasia.
Louie JD, Lauwers GY, Choi WT
HIF-1α in macrophage polarization: roles in immunometabolism and autoimmune diseases. Journal of leukocyte biology | 2026-06-18
Hypoxia-inducible factor-1α (HIF-1α) is a central regulator of cellular responses to hypoxia and plays a pivotal role in immune cell activation and functional reprogramming. This review summarizes how HIF-1α modulates inflammatory responses through metabolic regulation and examines its mechanistic involvement in autoimmune diseases. Under normoxic conditions, HIF-1α is rapidly degraded, whereas hypoxia, inflammation, or metabolic stress stabilizes the protein, allowing its nuclear translocation and activation of glycolysis-related genes. This shift drives immune cells from oxidative metabolism to glycolysis, supporting rapid energy production and promoting inflammation-associated functional states. Consequently, HIF-1α enhances the production of inflammatory mediators and forms positive feedback loops with inflammatory signaling pathways, influencing immune cell migration, survival, and function. Aberrant activation of HIF-1α is closely associated with disease activity in autoimmune disorders such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and multiple sclerosis, contributing to immune imbalance and tissue damage. However, its effects are context-dependent; in conditions like inflammatory bowel disease and uveitis, moderate activation may exert protective roles. Therefore, therapeutic strategies require precise, context-specific modulation rather than simple inhibition or activation. Although current drug development targeting HIF-1α focuses mainly on oncology, emerging approaches-including small molecule inhibitors, nanodelivery systems, and gene therapy-highlight its potential in autoimmune disease treatment. Overall, HIF-1α serves as a key link between hypoxia, metabolism, and immune regulation.
Li D, Pan X, He Z, Cui J, Zhu R, Guo D
[A potpourri of diagnoses-Unusual manifestations of a chronic inflammatory bowel disease : Case report]. Zeitschrift fur Rheumatologie | 2026-06-18
Inflammatory bowel diseases (IBD) are frequently associated with extraintestinal manifestations, which usually occur concomitantly with or following onset of an intestinal disease. The presence of multiple autoimmune manifestations preceding the diagnosis of IBD is rare and unusual. We report the case of a 22-year-old woman referred for rheumatological evaluation due to bilateral anterior uveitis. Her medical history included type 2 autoimmune pancreatitis and persistently elevated liver enzyme parameters. Further diagnostic work-up revealed primary sclerosing cholangitis. A few weeks later she developed bloody diarrhea and Crohn’s disease was confirmed histologically. A retrospective review of previous imaging studies showed findings consistent with small bowel inflammation prior to clinical manifestation. This case highlights the importance of interdisciplinary diagnostics in young patients presenting with multiple autoimmune manifestations. An underlying chronic inflammatory bowel disease should be considered even in the absence of gastrointestinal symptoms. HINTERGRUND: Chronisch-entzündliche Darmerkrankungen (CED) sind häufig mit extraintestinalen Manifestationen assoziiert. Diese treten meist im Verlauf oder zeitgleich mit der intestinalen Erkrankung auf. Das Vorliegen mehrerer assoziierter Autoimmunerkrankungen vor der Manifestation einer CED ist hingegen selten und ungewöhnlich. Wir berichten über eine 22-jährige Patientin, die initial wegen einer beidseitigen Uveitis anterior rheumatologisch vorgestellt wurde. In der Vorgeschichte bestanden eine Autoimmunpankreatitis Typ 2 sowie persistierend erhöhte Cholestaseparameter. Im weiteren Verlauf wurde eine primär sklerosierende Cholangitis diagnostiziert. Wenige Wochen später manifestierte sich klinisch und histologisch ein Morbus Crohn. Retrospektiv zeigten sich bereits zuvor bildgebende Hinweise auf eine entzündliche Dünndarmerkrankung. Der Fall unterstreicht die Bedeutung einer interdisziplinären Diagnostik bei jungen Patientinnen und Patienten mit multiplen Autoimmunmanifestationen. Eine zugrundeliegende chronisch-entzündliche Darmerkrankung sollte auch bei initial fehlender gastrointestinaler Symptomatik in Betracht gezogen werden.
Merwald-Fraenk H, Wiesent F, Burmester G, Hoff P
Bimekizumab Long-Term Safety and Efficacy Across the Spectrum of Axial Spondyloarthritis Over 3 Years: Results from Two Phase 3 Studies. The Journal of rheumatology | 2026-06-15
2-year safety and efficacy of bimekizumab, a dual IL-17A and IL-17F inhibitor, has been demonstrated across the full disease spectrum of axial spondyloarthritis (axSpA). We report bimekizumab long-term safety and efficacy over 3 years. Patients completing Week 52 of BE MOBILE 1 (nr-axSpA; NCT03928704) and BE MOBILE 2 (r-axSpA; NCT03928743) phase 3 studies could enter an ongoing open-label extension (OLE; NCT04436640) and continue receiving subcutaneous bimekizumab 160 mg every 4 weeks. Safety outcomes for patients receiving ≥1 bimekizumab dose, and efficacy outcomes for all randomised patients, are reported over 3 years (164 weeks [112-week OLE]). During the overall safety period, 90.4% (519/574) of patients had ≥1 treatment-emergent adverse event. Fungal infection exposure-adjusted incidence rate (EAIR)/100PY was 9.4 (majority Candida infections: 5.3; most mild/moderate, none serious/systemic). Inflammatory bowel disease and uveitis EAIR/100PY were 0.5 and 1.5. No major adverse cardiovascular events or deaths occurred. EAIRs, including for Candida infections, were generally lowest in the third year. 2-year efficacy with bimekizumab was sustained to Week 164. At Week 164, 57.0% achieved ASDAS low disease activity (<2.1), including 28.7% achieving ASDAS inactive disease (<1.3). Bimekizumab treatment also led to sustained improvements in BASFI and HRQoL scores and sustained control of MRI inflammation to Week 164, with 59.4% and 77.8% achieving SPARCC SIJ <2 and Berlin spine ≤2, respectively. Bimekizumab was well tolerated over 3 years, with no new safety signals observed. Across the full disease spectrum of axSpA, patients demonstrated sustained clinical efficacy and inflammation control over 3 years.
Baraliakos X, Deodhar A, van der Heijde D, Van den Bosch F, Magrey M, Maksymowych WP, Tomita T, Xu H, Coarse J, Prajapati C
Tracheobronchial stenosis as a rare extraintestinal manifestation of ulcerativecolitis: a case series with different therapeutic approaches.Case report Frontiers in medicine | 2026-06-03
Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by extraintestinal manifestations in nearly half of patients. Although pulmonary involvement has traditionally been considered rare, with a reported prevalence of less than 1%, recent studies indicate that subclinical airway abnormalities may occur in 40-60% of cases. Tracheobronchial stenosis is an uncommon but clinically significant extraintestinal manifestation that causes considerable diagnostic and therapeutic challenges. This report presents three female patients with UC who developed significant bronchial stenosis, predominantly affecting the left main bronchus. Notably, a temporal dissociation between intestinal and respiratory disease activity was observed; in two cases, airway symptoms developed years after the initial UC diagnosis, and in one case, symptoms appeared following total colectomy during intestinal disease remission. Histopathological examination consistently revealed chronic lymphoplasmacytic infiltrates and mucosal edema. Therapeutic responses varied considerably, ranging from active inflammation to irreversible fibrotic remodeling. One patient, unresponsive to systemic corticosteroids, required rigid bronchoscopy with balloon dilatation to restore airway patency. Another patient experienced rapid improvement with high-dose corticosteroids administered during a UC flare, while the third demonstrated partial improvement with persistent cicatricial stenosis. Early identification of tracheobronchial involvement in UC is important to prevent irreversible pulmonary damage. Given the rarity of this manifestation and the absence of standardized treatment protocols, multidisciplinary management incorporating medical therapy and interventional bronchoscopy is necessary to individualize patient care.
Zanini U, Franco G, Mazzotta SM, Geroli L, Bono F, Paciocco G, Faverio P, Luppi F, Marruchella A
Multi-layered functional genomics prioritizes candidate effectors and regulatory mechanisms of ankylosing spondylitis.Meta-analysis Frontiers in immunology | 2026-06-01
Ankylosing spondylitis (AS) is a chronic inflammatory arthropathy with heritability estimated at approximately 90%, yet the effector genes and regulatory mechanisms beyond the well-established HLA-B*27 association remain incompletely defined. Translating GWAS-identified loci into biological insight requires integration of calibrated association statistics, gene-level prioritization, fine-mapping, molecular prediction, and experimental follow-up. We performed a GWAS meta-analysis of 7,551 AS cases and 1,258,581 controls from the Million Veteran Program, FinnGen, and UK Biobank whole-genome sequencing cohorts. The post-GWAS analysis combined causal transcriptome-wide association study (cTWAS) across four immune-relevant tissues, colocalization, four-method fine-mapping, Geneformer V2 in-silico perturbation, AlphaGenome variant-effect prediction, cross-trait LD-score regression (LDSC), pathway enrichment, structured druggability assessment, and siRNA knockdown in Jurkat T cells. We added LDSC calibration, per-cohort Q-Q plots, heterogeneity summaries, and leave-one-cohort-out sensitivity analyzes for revised quality control. The meta-analysis identified 30 genome-wide significant loci harboring 26,178 significant variants. After LDSC-compatible quality control, the meta-analysis showed lambda_GC = 1.09, LDSC intercept = 1.045 (SE = 0.009), and attenuation ratio = 0.365 (SE = 0.075); per-cohort lambda_GC values were 1.027, 1.080, and 1.018 for MVP, FinnGen, and UKB-WGS, respectively. cTWAS prioritized 64 causal-candidate genes (posterior inclusion probability [PIP] > 0.5), with gene expression explaining 19.5% of AS heritability. Seven genes showed convergent cTWAS and colocalization evidence (TBKBP1, TIMD4, HABP4, XCL1, USP22, ABO, ACTA2). Four-method fine-mapping identified 64 consensus variants, while heterogeneity and leave-one-cohort-out analyzes highlighted cohort-sensitive signals, particularly in the MHC and other high-I2 regions. Cross-trait LDSC showed positive genetic correlations with inflammatory bowel disease and psoriasis, but not rheumatoid arthritis or the available uveitis proxy. siRNA knockdown provided functional support for TBKBP1 and XCL1 in Jurkat T cells, while TIMD4 behaved as a context-specific myeloid/T-cell contrast. This convergent evidence framework prioritizes AS candidate genes and regulatory variants while separating statistical prioritization from experimental support. The revised analyzes strengthen calibration, heterogeneity reporting, cross-disease context, and translational interpretation, nominating immune and regulatory hypotheses for follow-up rather than definitive therapeutic targets.
Meng F, Chen L, Li M, Zhang Q, Wang P, Lin R, Liu J, Yuan Z, Chen K, Li Z
AI & Machine Learning (5 papers)
Machine learning-based identification of a metabolic cell death gene signature for assessing disease activity and immunological landscape in inflammatory bowel disease. Scientific reports | 2026-06-15
Inflammatory bowel disease (IBD) is characterized by a refractory, relapsing inflammatory state driven by a multifaceted and poorly understood interplay between host mucosal metabolic disturbances and immune microenvironment dysregulation. To uncover robust non-invasive diagnostic indicators, this study implemented an integrated analytical framework combining advanced machine learning feature selection, penalized logistic regression modeling, and leave-one-dataset-out cross-validation to construct a novel diagnostic signature derived from metabolic cell death-related genes (MCDRGs). Systematic multiple-testing correction and rigorous data harmonization were applied across all independent discovery and validation cohorts to control for potential batch effects. Through this approach, we successfully identified a core three-gene candidate panel comprising indoleamine 2,3-dioxygenase 1 (IDO1), lipocalin 2 (LCN2), and solute carrier family 6 member 14 (SLC6A14). Methodologically, we demonstrated that the initial near-perfect apparent discrimination within the discovery cohort was mathematically attributable to quasi-complete data separation rather than systemic model overfitting. This identified signature exhibited consistent cross-cohort validation and correlated tightly with the coordinated infiltration and functional states of multiple mucosal immune cell subsets. Furthermore, independent clinical assays substantiated the synchronized elevation of these markers during active clinical phases, while orthogonal single-cell RNA-sequencing confirmed their prominent, cell-type-specific enrichment within the myeloid, epithelial, and stromal compartments of inflamed intestinal mucosa. Collectively, the identified MCDRGs, IDO1, LCN2, and SLC6A14, link metabolic dysregulation, immune infiltration, and regulated cell death, offering insights into IBD pathophysiology and providing a transcriptomic candidate signature with exploratory diagnostic potential for IBD stratification.
Xu F, He Z, Li Q, Chen Y
Investigating Immune Microenvironment of Inflammatory Bowel Disease and the Mitochondrial Metabolism-Related Molecular Mechanisms: Combining a Multiomics Approach and Experimental Validation. Omics : a journal of integrative biology | 2026-06-15
Inflammatory bowel disease (IBD) is a chronic and recurrent gastrointestinal disease, the pathogenesis of which has not been fully elucidated. Increasing evidence suggests that the disorder of mitochondrial metabolism is closely related to the pathogenesis of IBD, but its specific regulatory network and key genes remain to be further investigated. IBD-related transcriptome datasets (GSE3365 and GSE75214) and single-cell sequencing dataset (GSE134809) were obtained from the Gene Expression Omnibus database. Differentially expressed genes and hub genes were identified through differential expression analysis and weighted gene co-expression network analysis, and candidate genes were obtained by intersecting these with mitochondrial metabolism-related genes, followed by functional enrichment analysis. Machine learning algorithms were used to screen key genes and construct risk prediction models. Additionally, analysis of GSE134809 single-cell data identified characteristic cell types and expression distribution of key genes in IBD and explored communication between different cell types. Furthermore, immune cell infiltration, competitive endogenous RNA (ceRNA) network, and transcription factor prediction were performed. Finally, the diagnostic performance of key genes was validated in GSE75214 and reverse transcription-quantitative polymerase chain reaction. Two key genes, mitochondrial ribosomal protein L35 (MRPL35) and MRPL39, were identified, which were downregulated in IBD, and had good diagnostic potential. Single-cell analysis revealed that key genes were predominantly highly expressed in mononuclear phagocyte (MNP) cells. MNP cells communicated with other cells through receptor ligands including MIF-(CD74 + CXCR4), MDK-SDC1, and ITGB2-ICAM2, which are complexly related to mitochondrial metabolism. With the progression of IBD, infiltration levels of resting natural killer cells, naive B cells, M2 macrophages, and naive CD4 T cells decreased, and correlations between different cells continuously changed. A ceRNA network centered on XIST, hsa-miR-103a-3p, and MRPL35 was constructed. Additionally, therapeutic drugs targeting key genes were predicted, including cimetidine, eugenol, chlortetracycline, vincristine, irinotecan, bisacodyl, and sulpiride, with molecular docking validating high affinity between these drugs and key targets. This study constructed a multiomics integrated analysis strategy and identified MRPL35 and MRPL39 as potential markers and therapeutic targets, providing new insights for the diagnosis and treatment of IBD.
Li H, Wu X, Wu Q, Wang J
More than a gut feeling: large language model thematic analysis of social media posts from inflammatory bowel disease patient communities. Clinics and research in hepatology and gastroenterology | 2026-06-15
Inflammatory bowel disease (IBD) morbidity extends beyond gastrointestinal symptoms and complications. We aimed to describe IBD patient experience through an analysis of online patient communities. Thematic analysis of 104,123 posts from three IBD patient groups on the social media platform Reddit between 2015-2024 was undertaken using a large language model (LLM) based on the GPT-4 architecture. The Valence Aware Dictionary and Sentiment Reasoner (VADER) tool was used to assess sentiment analysis. Of 15 core themes identified by LLM analysis, the most prevalent were ‘Diagnosis struggles’ (13.1%), ‘Peer advice’ (12.5%), and ‘Mental health & Coping’ (11.8%). Results were validated using a natural language processing model and human chart review, with concordance of 88.3% and 87.0%, respectively. The themes that generated the most community engagement were ‘Relationships’ (15.3 mean comments), ‘Humor & Embarrassment’ (12.8), and ‘Hope & Remission’ (12.6). ‘Fatigue & Pain’ was associated with the worst sentiment (-0.44), and ‘Hope & Remission’ with the best one (+0.43). Posts by self-identified females were more likely to focus on ‘Mental Health & Coping’ (11.7%vs 10.0%, p = 0.003), while self-identified males were more likely to post on ‘Medication Experiences’ (13.3%vs 11.7%, p = 0.003) and ‘Surgery’ (2.4%vs 1.7%, p = 0.003). Over the years, ‘Surgery’ posts decreased by 50%, while ‘Fear of the Future’ and ‘Diagnosis Struggles’ posts increased by 23% and 21%, respectively. Patient posting and engagement focus on psychosocial and emotional disease burden, rather than on gastrointestinal morbidity. These results can inform healthcare professionals caring for patients with IBD.
Cohen RT, Tov EY, Shepshelovich D
Investigation of the molecular network underlying PET-MPs-induced inflammatory bowel disease via integrated machine learning and molecular docking approaches. Scientific reports | 2026-06-14
Polyethylene terephthalate microplastics (PET-MPs), as environmental contaminants, have raised significant concerns due to their potential toxicity, leading to serious environmental pollution and health issues. However, their impact on inflammatory bowel disease (IBD) remains poorly elucidated. This study aims to investigate the potential molecular mechanisms linking PET-MPs to IBD pathogenesis. Multiple datasets were employed to identify Crohn’s disease (CD)- and ulcerative colitis (UC)-associated targets. Multi-machine learning approaches were combined with molecular docking of a PET-related compound to evaluate potential binding interactions with the identified hub targets. This study delineated 9 putative targets associated with PET-MPs-related CD pathogenesis and 17 potential targets associated with UC pathogenesis. For CD, GBM showed the best performance among all models, with a mean ROC-AUC of 0.862; for UC, RF performed best, with a mean ROC-AUC of 0.806, based on both training and validation sets. Multi-machine learning analysis identified 14 hub genes as candidate key regulatory factors. SHAP analysis highlighted their significant contributions to the model predictions. Molecular docking simulations suggested favorable binding affinities between a PET-related compound and the hub targets. This study suggests that PET-MPs may contribute to IBD pathogenesis by potentially interacting with 14 machine learning-prioritized hub genes. Molecular docking analyses indicated predicted high-affinity binding between a PET-related compound and these targets. Collectively, these findings provide a hypothesis-generating framework for investigating the potential role of PET-MPs in IBD progression.
Ye J, Lu Q, Wang H, Chen Z, Ran S
Prediction of inflammatory bowel disease recurrence risk based on multi-omics integration and machine learning models. Computational biology and chemistry | 2026-06-11
Postoperative recurrence remains a major clinical challenge in inflammatory bowel disease (IBD), while robust molecular predictors with clear biological and causal relevance are still lacking. This study aimed to identify and validate recurrence-associated genes in IBD using an integrative multi-level analytical framework. Two independent postoperative IBD transcriptomic datasets were analyzed to identify recurrence-related differentially expressed genes and co-expression modules. Mendelian randomization (MR) and colocalization analyses were subsequently applied to prioritize genes with potential causal relevance. Key genes were validated by quantitative real-time PCR (qRT-PCR) in independent clinical ileal tissue samples. Machine learning models were constructed and externally validated in a real-world clinical cohort to assess recurrence prediction performance. Integrative analyses identified 253 recurrence-related genes, including 73 shared upregulated genes, 31 shared downregulated genes, and 157 shared module genes. MR analysis identified six candidate genes, among which KLHL24, NPC1, and PSMG1 showed strong colocalization evidence (PP.H4 > 0.95). qRT-PCR validation confirmed that KLHL24 and NPC1 were significantly downregulated, whereas PSMG1 was significantly upregulated in recurrent ileal tissues compared with non-recurrent tissues (all P < 0.001). In the external validation cohort of 178 patients, the logistic regression model showed the highest predictive performance, with an AUC of 0.801 (95% CI: 0.781-0.820), sensitivity of 0.712, and specificity of 0.741, followed by random forest, XGBoost, and decision tree models with AUCs of 0.792, 0.787, and 0.750, respectively. This study delineates molecular features associated with postoperative recurrence in IBD and identifies key genes supported by transcriptomic, genetic, and clinical evidence, providing a robust basis for recurrence risk stratification.
Li H, Cao M, Cao M
Intestinal Ultrasound (IUS) (3 papers)
Development and validation of the SYSU-score for MRI-based transmural healing assessment in Crohn’s disease: a dual-center study. European radiology | 2026-06-19
Standardizing magnetic resonance enterography (MRE)-defined transmural healing (TH) remains challenging in Crohn’s disease (CD) despite its prognostic superiority. We aimed to evaluate seven conventional MRE-defined TH criteria and develop a machine-learning-optimized model for improved TH assessment. In this double-center study, 467 active CD patients with 1263 MRE scans were stratified into three cohorts. Cohort 1 (n = 341) enabled retrospectively dual-metric comparison (attainment rate/prognostic protection) of seven MRE-defined TH criteria. Leveraging their strengths, we developed five machine-learning models for TH assessment to identify the optimal one. Semi-external validation was performed in prospective Ustekinumab (n = 92) and Upadacitinib (n = 34) cohorts. Among seven conventional TH criteria, magnetic resonance index of activity (MaRIA), C-score, and simplified MaRIA (sMaRIA) demonstrated higher attainment rates (23.75%/28.74%/41.64%) and lower disease progression rates (14.81%/18.37%/25.35%). Random forest (RF) model showed the most favorable overall performance across cohorts: Cohort 1 (AUC, 0.82 vs. 0.71-0.81), Ustekinumab (AUC, 0.83 vs. 0.73-0.81), and Upadacitinib (AUC, 0.80 vs. 0.58-0.80) cohorts. Dual-metric evaluation identified the RF model and C-score as clinically applicable tools. Notably, the RF model (namely SYSU-score) was more strongly associated with lower progression risk than C-score: in the Ustekinumab cohort, SYSU-score-defined TH showed lower disease progression risk (HR = 0.07, p < 0.001) than C-score (HR = 0.15, p < 0.001); Upadacitinib cohort validated SYSU-score as the only system significantly associated with lower progression risk (HR = 0.20, p < 0.05). We established a validated machine-learning-derived TH criterion integrating the strengths of conventional MRE-defined systems. SYSU-score-defined TH status was associated with lower progression risk with robust prognostic discrimination, advancing standardized TH assessment for clinical implementation. Question Among available MRI-based transmural healing (TH) criteria for Crohn’s disease (CD), which are the most clinically applicable, and can a new model improve standardized prognostic assessment? Findings MaRIA, C-score, and sMaRIA showed relatively favorable clinical applicability, and the machine-learning-derived SYSU-score demonstrated robust prognostic performance in internal and semi-external validation. Clinical relevance SYSU-score may support more standardized MRI-based assessment of TH and improve risk stratification for disease progression in patients with CD.
Zheng Q, Zhao Q, He W, Huang L, Shen X, Wu L, Ke Y, Zheng W, Wang Y, Chen Y
Complicated Acute Appendicitis Conservatively Treated in Two Patients With Crohn’s Disease: The Role of Intestinal Ultrasound and Contrast-Enhanced Ultrasound.Case report Journal of clinical ultrasound : JCU | 2026-06-17
According to the most recent guidelines, uncomplicated acute appendicitis could be treated conservatively using broad-spectrum antibiotics, but if radiological signs of appendix rupture are present, appendectomy should be considered as first-line treatment. There is limited evidence in literature regarding the non-operative management of complicated acute appendicitis, particularly in the subset of patients with Crohn’s disease. Intestinal and contrast-enhanced ultrasound appear pivotal to both diagnosing complications and promptly identifying the non-responding patients. We describe two cases of complicated acute appendicitis, successfully treated with broad-spectrum antibiotic therapy and tight monitoring with both intestinal and contrast-enhanced ultrasound, in patients with Crohn’s disease.
Giovanni C, Daniele G, Kim N, Francesco C, Piergiorgio D, Giovanni M
Microcystic lymphatic malformation of the small intestine presenting as acute abdominal pain in a 5-year-old boy: a case report and review of the literature. Journal of medical case reports | 2026-06-15
Lymphatic malformations are rare benign congenital anomalies of the lymphatic system, most commonly affecting the head and neck. Gastrointestinal involvement is uncommon, and lymphatic malformations of the small intestine are particularly rare. Microcystic lymphatic malformations infiltrating the bowel wall may present with nonspecific clinical and radiological features, making preoperative diagnosis challenging. Reporting such cases is important to raise awareness of this rare entity as a potential cause of acute abdominal pain in children. A 5-year-old Vietnamese boy presented with acute onset abdominal pain, vomiting, and fever of 1-day duration. Physical examination revealed mild lower abdominal tenderness without a palpable mass. Abdominal ultrasonography demonstrated a mixed echogenic cystic lesion, while contrast-enhanced computed tomography revealed a segment of small intestine with irregular wall thickening, scattered calcifications, and tortuous intramural vessels. Differential diagnoses included vascular malformation, inflammatory bowel disease, and intestinal infection. Due to the acute presentation and inconclusive imaging findings, exploratory laparotomy was performed. Intraoperatively, a markedly thickened and hypervascularized segment of small bowel with dark purple discoloration was identified and resected, followed by primary end-to-end anastomosis. Histopathological examination revealed numerous small lymphatic channels infiltrating all layers of the intestinal wall with focal intralesional hemorrhage, confirming the diagnosis of microcystic lymphatic malformation. The postoperative course was uneventful, and the patient recovered well without complications. Microcystic lymphatic malformation of the small intestine is a rare but important differential diagnosis in children presenting with acute abdominal pain and localized bowel wall thickening. Because clinical and imaging findings are often nonspecific, definitive diagnosis usually relies on histopathological examination. Complete surgical excision provides both diagnostic confirmation and curative treatment, with excellent short-term outcomes.
Pham TN, Nguyen H, Vu TM, Ban HT
Pediatric IBD (3 papers)
Peripheral Immune Challenge Drives Enteric α-Synuclein and Tau Pathology in LRRK2 G2019S Mice. Aging and disease | 2026-06-12
Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by α-synuclein aggregation and dopaminergic neuron loss. Non-motor symptoms, including gastrointestinal dysfunction, often precede motor onset, suggesting a gut origin of pathology. LRRK2 variants increase susceptibility to both PD and Crohn’s disease, pointing to a potential link between LRRK2 hyperactivity and early intestinal abnormalities; however, it remains unclear how LRRK2 contributes to enteric α-synuclein pathology and co-occurring proteinopathies. In this study, we investigated the interaction between chronic peripheral inflammation and the LRRK2 G2019S variant using a longitudinal mouse model combining ageing and repeated low-dose LPS exposure. We quantified peripheral cytokine levels, colonic immune cell infiltration (CD4⁺ T cells and macrophages), and the temporal progression of enteric α-synuclein and tau pathology across different ages. Our results showed that chronic LPS exposure induced an age-dependent increase in circulating cytokines and colonic immune infiltration in LRRK2 G2019S mice, accompanied by enhanced enteric α-synuclein accumulation and phosphorylation, alongside elevated tau phosphorylation, compared with wild-type controls. Notably, total neuronal counts remained stable, indicating a distinct pre-degenerative stage of pathology. Overall, our findings demonstrate that chronic peripheral inflammation synergizes with LRRK2 G2019S to trigger early intestinal inflammation and α-synuclein/tau co-pathology in the absence of overt neurodegeneration. These results suggest that LRRK2 acts as a critical link between systemic immunity and neuronal protein homeostasis, increasing the vulnerability of the gut to inflammatory stress. Characterizing this early pathological window provides key insights into PD initiation and highlights the gut as a promising target for early therapeutic intervention.
Giachino C, Bertoli F, Tirolo C, Giuliano C, Mearelli M, Jakobi M, Schneiderhan-Marra N, L’Episcopo F, Deleidi M
Stress-induced IL-6 regulation in pediatric bone growth disorders: current insights and therapeutic strategies.Review Frontiers in endocrinology | 2026-06-02
Stress-induced upregulation of interleukin-6 (IL-6) signaling and its downstream pathophysiological consequences have garnered considerable attention in recent years. However, no comprehensive review has specifically examined the association between stress-induced IL-6 and its implications for bone health in children. During childhood, linear growth and peak bone mass acquisition are tightly regulated processes. Hence, this review aims to investigate current evidence on stress-induced IL-6 upregulation and its detrimental effects on pediatric bone health. Findings from animal models, knockout studies, pediatric inflammatory disorders, including juvenile idiopathic arthritis, pediatric systemic lupus erythematosus and inflammatory bowel disease, and models of metabolic stress collectively demonstrate that stress triggers IL-6, thereby impairing skeletal growth and increasing fragility. Data shows that persistent IL-6 upregulation not only disrupts the normal functioning of growth hormone, insulin-like growth factor-1 (GH/IGF-1) axis, enhances receptor activator of nuclear factor kappa-B ligand (RANKL)-mediated osteoclastogenesis, and promotes bone marrow adiposity. Further, stress-induced high levels of IL-6 adversely affect the skeletal, immune, and endocrine systems, thereby compromising skeletal development and bone growth in children. Elevated systemic or local IL-6 levels may exert direct deleterious effects on bone by impairing stem cell differentiation and inhibiting the proliferation and maturation of growth plate chondrocytes, ultimately restricting longitudinal bone growth. Moreover, elevated IL-6 levels may also impair muscle health and crosstalk between muscle and bone, thereby compromising skeletal integrity. Collectively, these findings underscore the need for integrative therapeutic strategies that target inflammation and redox imbalance in bone and other tissues, particularly in children. Better understanding stress-induced IL-6 dysregulation is critical for pediatric bone development and long-term skeletal health.
Sohail Z, Hadi NBA, Rehman A, Asghar M, Zaman F
Intestinal spirochetosis in the modern era: a decade-long clinicopathologic study. American journal of clinical pathology | 2026-06
Intestinal spirochetosis (IS) is infrequently identified in about 1% of human colonic biopsy specimens. On routine sections, it is diagnosed by identifying a thick band of basophilia on the apical surface of colonic mucosa. Intestinal spirochetosis is caused by Brachyspira pilosicoli and Brachyspira aalborgi, but whether it represents a commensalism or a pathogenic process remains debated. We studied 175 cases of IS diagnosed at our institution over a 10-year period. The clinicopathologic features were reviewed using hematoxylin and eosin (H&E)-stained slides, along with the results from histochemical and immunohistochemical analyses. All cases were diagnosed by colonoscopic biopsy, except for 1 case. Indications for colonoscopy were unexplained diarrhea (48.6%), colorectal cancer screening (36%), rectal bleeding (6.3%), abdominal pain (4%), follow-up for ulcerative colitis (4%), Crohn disease (0.6%), and constipation (0.6%). Associated significant clinical conditions included HIV-positive status (14.3%), diabetes mellitus (1.7%), post-liver transplant (0.6%), retroperitoneal liposarcoma (0.6%), prostate cancer (0.6%), and Kaposi sarcoma (0.6%). Pathologic changes in background colonic mucosa included unremarkable (89%), active inflammation (6%), hyperplastic polyp (1.7%), tubular adenoma (1.7%), and Trichuris trichiura infestation (0.6%). On H&E, all cases had the characteristic basophilic hue on the epithelial surface of colonic mucosa. Intestinal spirochetosis in our study had a striking male predominance and affected both immunocompetent and immunosuppressed individuals. Nearly two-thirds of the patients were symptomatic, indicating that IS is likely a pathogenic infection of low virulence. Histologically, IS can involve normal, inflamed, and dysplastic epithelium.
Dhorajiya P, Singal M, Mannan R
Drug Safety & Pharmacovigilance (2 papers)
Microbial metabolites at the front line: Orchestrating gastrointestinal and systemic barrier immunity across the lifespan.Review★ Cell reports | 2026-06-15
Microbiota-derived metabolites are central mediators between commensal microbes and host immune system at mucosal barrier surfaces. Insights from mouse models have revealed precise molecular mechanisms by which numerous metabolites, including short-chain fatty acids, tryptophan catabolites and bile acid derivatives, regulate epithelial integrity, innate immune tone, and adaptive immunity and tolerance. Parallel studies in humans increasingly confirm these pathways and link metabolite dysregulation to diseases, such as inflammatory bowel disease, asthma, and atopic dermatitis. This review synthesizes current understanding of how microbial metabolites orchestrate gastrointestinal barrier immunity, while also integrating emerging insights into the gut-lung and gut-skin axes. Crucially, we examine these interactions through a developmental lens, highlighting how metabolite exposure during critical early-life “windows of opportunity” shapes long-term immune trajectories. We integrate evidence from experimental models and human data to highlight conserved mechanisms, species-specific divergences, and the therapeutic potential of targeting these metabolic pathways as strategies to promote barrier health and durable immune homeostasis.
Koren O, Collado MC, Chassaing B, Silverman MA, Konnikova L
Design, synthesis, and biological evaluation of C-28 carboxyl derivatives of Hederacoside C as anti-inflammatory agents for acute lung injury. Bioorganic chemistry | 2026-06-10
Hederacoside C, a bioactive triterpenoid saponin isolated from the dried roots of the Ranunculaceae plant Pulsatilla chinensis, has demonstrated therapeutic efficacy in murine models of nephritis, acute lung injury, and inflammatory bowel disease. However, its further development as a drug candidate has been hampered by hemolytic toxicity and poor oral bioavailability. Based on published evidence that the free carboxyl group at the C-28 position is closely associated with hemolytic activity, a series of C-28 carboxyl derivatives was rationally designed and synthesized with the aim of attenuating hemolytic liability while preserving or enhancing anti-inflammatory potency. Following in vitro anti-inflammatory evaluation and cytotoxicity assessment, compound HSC-4 was identified as the most promising candidate for further in vivo pharmacological studies. Notably, HSC-4 exhibited significant anti-inflammatory efficacy in both a murine systemic sepsis model and an acute lung injury model. An acute toxicity study further demonstrated that HSC-4 did not cause significant hepatotoxicity or nephrotoxicity in KM mice at doses up to 400 mg/kg over five consecutive days. These findings suggest that HSC-4 represents a promising lead compound for the development of novel anti-inflammatory therapeutics, pending further hemolytic activity assessment and pharmacokinetic characterization.
Meng F, He J, Li H, Li X, Li Z, Zhang J, Li J, Feng Y, Zhu J, Fang Y
Endoscopy & Imaging (non-IUS) (2 papers)
Association analysis of short-chain fatty acid levels and intestinal mucosal healing in ulcerative colitis patients.★ Inflammatory bowel diseases | 2026-06-13
Intestinal mucosal healing is a key indicator for evaluating therapeutic efficacy and predicting long-term prognosis in ulcerative colitis (UC). Short-chain fatty acids (SCFAs) play an important role in maintaining intestinal homeostasis and promoting mucosal repair; however, their quantitative association with UC mucosal healing has not been fully elucidated. This study aimed to investigate the association between SCFA levels and endoscopic mucosal healing in UC patients and evaluate their clinical value as predictive biomarkers. This prospective cohort study enrolled 154 UC patients from January 2024 to March 2025, who were divided into a mucosal healing group (n = 68) and a non-healing group (n = 86) according to Mayo endoscopic scores, with an additional 50 healthy controls. Endoscopic evaluations were independently scored by two experienced gastroenterologists with substantial inter-rater reliability (κ = 0.82). Gas chromatography-mass spectrometry was used to detect fecal SCFA concentrations, and real-time quantitative PCR (PCR stands for Polymerase Chain Reaction, a core molecular biology technique that allows for the rapid and specific amplification of specific DNA or RNA fragments in vitro) was employed to detect the expression levels of SCFA transporter protein SLC16A1 and metabolic enzyme genes in mucosal tissues. The association between SCFA levels and mucosal healing indicators was analyzed using multiple logistic regression adjusted for age, gender, disease duration, disease extent, and current medications. The total fecal SCFA concentration in UC patients was significantly lower than that in healthy controls (P < .001). The butyrate concentration in the mucosal healing group was significantly higher than that in the non-healing group ([16.8 ± 7.3] vs [10.2 ± 4.6] mmol/kg, P < .001). The SLC16A1 mRNA expression level in the mucosal healing group was 2.3-fold higher than that in the non-healing group, while ACSM3 and ACADS expression levels were elevated by 1.8-fold and 1.6-fold, respectively (all P < .001). Fecal butyrate concentration showed a significant negative correlation with Mayo endoscopic score (r = -0.647, P < .001). Multiple regression analysis revealed that fecal butyrate concentration was an independent predictor of mucosal healing (OR = 1.18, 95% CI: 1.09-1.28, P < .001). Receiver operating characteristic analysis demonstrated that butyrate had an area under the curve (AUC) of 0.847 for predicting mucosal healing, with a sensitivity of 76.5% and specificity of 81.4%. A combined model incorporating butyrate, C-reactive protein, and corticosteroid use achieved superior diagnostic performance (AUC = 0.896). The associations remained consistent across different disease extents and medication subgroups. Fecal SCFA levels in UC patients, particularly butyrate concentration, are closely associated with the degree of intestinal mucosal healing. Fecal butyrate concentration can serve as a non-invasive biomarker for assessing mucosal healing status in UC patients, providing objective evidence for individualized therapeutic strategy development. This prospective cohort study included 154 UC patients and 50 healthy controls to explore short-chain fatty acid (SCFAs) association with intestinal mucosal healing. UC patients had lower fecal SCFAs; the mucosal healing group showed higher butyrate and elevated butyrate metabolism-related gene (SLC16A1, ACSM3, ACADS) expression. Fecal butyrate independently predicted mucosal healing (area under the curve [AUC] = 0.847), with a combined model (butyrate + C-reactive protein + corticosteroid use) showing better performance (AUC = 0.896). Conclusion: Fecal butyrate is a non-invasive biomarker for the UC mucosal healing, aiding personalized treatment and reducing endoscopy reliance.
He BQ, Lai XQ, Yang X, Zhou J
Virtual chromoendoscopy with linked color imaging versus dye-chromoendoscopy in the surveillance of patients with long-standing colonic inflammatory bowel disease.★ Journal of Crohn’s & colitis | 2026-06
Surveillance colonoscopy programmes in inflammatory bowel disease (IBD) are associated with reduced colorectal cancer (CRC) incidence. This study aims to compare the performance of virtual chromoendoscopy (VCE) using linked color imaging (LCI) and dye-chromoendoscopy (DCE) with methylene blue for the detection of colonic neoplastic lesions during surveillance colonoscopy in patients with IBD. This single-center retrospective cohort study included patients with colonic IBD undergoing CRC surveillance colonoscopy between June 2018 and December 2024. The primary outcome was the total neoplastic lesions detected in each group. The secondary outcome was the neoplastic lesions detection rate. Propensity-score matching and multivariable Poisson and logistic regression were used to adjust for baseline differences and identify independent predictors. 311 patients were included (112 DCE, 199 LCI). The mean number of neoplastic lesions identified per colonoscopy was 0.116 with DCE and 0.085 with LCI (P = .472). Similarly, the neoplasia detection rate was comparable between techniques (8.03% for DCE vs 7.53% for LCI; odds ratio [OR] 1.07, 95% confidence interval [CI], 0.45-2.54, P = .874). After 1:1 propensity score matching, the chromoendoscopy modality (DCE vs LCI) was not associated with the total number of neoplastic lesions (IRR 0.77; 95% CI, 0.34-1.78; P = .543) and with the neoplastic lesions detection rate (OR 0.58; 95% CI, 0.21-1.65; P = .310). LCI-based VCE provides a neoplastic yield comparable to traditional DCE in patients with long-standing colonic IBD undergoing surveillance colonoscopy. As with other VCE modalities, LCI may be adopted as an alternative to DCE for dysplasia surveillance in IBD.
Gabbiadini R, Franchellucci G, Minini F, Dal Buono A, Privitera G, Spadaccini M, Migliorisi G, Petronio L, Farinola V, Di Martino A
Guidelines & Consensus (2 papers)
Chronic nonbacterial osteomyelitis and inflammatory bowel disease in children: A French national cohort. Journal of pediatric gastroenterology and nutrition | 2026-06-16
Inflammatory bowel disease (IBD) and chronic nonbacterial osteomyelitis (CNO) is a rare association. Its prevalence is probably underestimated due to low awareness among clinicians. The aim of this study was to describe the French pediatric national cohort and to estimate the incidence of CNO among IBD. We retrospectively collected all reports of IBD-CNO association from pediatric gastroenterological and rheumatologic units between 2000 and 2024. We analyzed demographic data; age of the onset; IBD type; CNO localizations; dermatological lesions; explorations results; medications; follow-up. Incidence was estimated using French regional inception population-based cohort EPIMAD data. Thirty-seven patients were identified. Median age at the onset was 13.5 years (interquartile range [IQR] 11.5-14.5). CNO diagnosis preceded IBD in 11 cases, followed it in 13 cases, while 13 IBD-CNO cases were diagnosed simultaneously (median interval 1 year). IBD included 25 Crohn’s disease, 10 ulcerative colitis, 2 IBD-unclassified. Bone localizations predominated in lower limbs and pelvis (75.3%). Fourteen children (37.8%) had dermatological lesions. At last follow-up (median 3 years, IQR 1.25-4.75), 28 patients (75.7%) were in IBD-CNO remission, having mostly anti-tumor necrosis factor (TNF)-α (p = 0.041, 82.1% remission, 44.4% relapse) in monotherapy (60.7%). We estimate the incidence of this association among French pediatric IBD at 1 case for 20,000 patients-year. This study describes a large national cohort of pediatric IBD-CNO association. Gastroenterologist should request a whole body-magnetic resonance imaging when IBD patients present chronic bone pain. Multidisciplinary management involving rheumatologists and dermatologists is recommended. Most patients responded to anti-TNF-α antibodies, which could avoid bone complications.
Bertrand V, Pigneur B, Frémond ML, Coopman S, Leguevaques D, Dusser P, Breton A, Benezech A, Rebelle C, Sabard A
[Expert consensus on endoscopic diagnosis and treatment for inflammatory bowel disease in children (2026)]. Zhonghua er ke za zhi = Chinese journal of pediatrics | 2026-06-16
炎症性肠病（IBD）是一种免疫介导的慢性肠道炎症性疾病，病程迁延、反复发作，可影响患儿生长发育及生活质量，加重家庭的经济负担。消化内镜在其诊断、病情评估、疗效监测及并发症处理中具有关键作用。当前，我国儿童IBD内镜诊疗实践仍存在不规范之处，尚无系统、全面的儿童IBD内镜诊疗专家共识。为此，中华医学会儿科学分会消化学组与中华儿科杂志编辑委员会组织专家制订了“儿童炎症性肠病内镜诊疗专家共识（2026）”，旨在为我国儿童IBD的规范化内镜诊疗提供指导。.
DOI: 10.3760/cma.j.cn112140-20260401-00259 | View on PubMed →
Pregnancy & Reproductive Health (2 papers)
Crohn Disease Presenting as Vaginal Discharge in a Patient With Systemic Lupus Erythematosus. Pediatrics | 2026-06-17
Crohn disease (CD), a subtype of inflammatory bowel disease, may be complicated by extraintestinal manifestations. Although cutaneous findings are among the most frequent, metastatic Crohn disease (MCD), defined as mucocutaneous CD at sites noncontiguous with the gastrointestinal tract, is rare. Children with MCD are more likely than adults to develop genital inflammation. Case reports describe the vulva, scrotum, and penis as common locations of involvement in children with genital MCD. We report a case of a pediatric patient with systemic lupus erythematosus who developed vaginal discharge as a presenting symptom of MCD in the absence of an anorectal-vaginal fistula. We describe an unusual combination of clinical features and intend to improve awareness of uncommon extraintestinal manifestations of CD.
Ries AG, Samalik J, Nocton JJ, Francis J, Arkin LM, Seroogy CM, Young KE, Chiu YE
Medical invalidation and life validation in individuals with Crohn’s disease in Japan: A qualitative study. Patient education and counseling | 2026-06-10
This study examined how medical invalidation and “life validation” are enacted in the narratives of individuals living with Crohn’s disease in Japan, and how these processes shape care trajectories and life possibilities. We analyzed narrative interviews from DIPEx-Japan involving all 35 adults with Crohn’s disease (43% women aged 24-59 years) in the Crohn’s disease module who participated in semi-structured interviews on symptom onset, diagnosis, treatment, and everyday life. Verbatim transcripts were analyzed using reflexive thematic analysis within a critical realist orientation combined with an empathic, interpretive stance, using medical invalidation as a sensitizing concept. Four themes were generated. First, disabling abdominal pain, diarrhea, and anemia were repeatedly psychologized or pathologized as “stress” or “mental problems” that delay diagnosis and erode trust in bodily sensations. Second, efforts to sustain work, study, family roles, and self-care were downplayed as “not important” or “unnecessary visits,” thereby diminishing patients’ social selves. Third, poorly communicated diagnostic uncertainty, lack of access to test results, and inadequate handovers positioned patients to continually “prove” themselves, leading to withdrawal from care. Fourth, relationships in which clinicians, occupational health physicians, and employers started from patients’ hopes regarding work, education, and pregnancy and adjusted treatment and work arrangements accordingly were experienced as “life validation” that sustained autonomy and future-oriented life projects. Medical invalidation in Crohn’s disease extends beyond symptom assessment to everyday roles, diagnostic and treatment trajectories, and future choices, and is shaped by cultural norms and institutional practices. We propose “life validation” as an emergent analytic construct describing relational practices that begin from patients’ life hopes. Supporting life validation-starting from patients’ life hopes, communicating uncertainty with “warm handovers,” and embedding attention to invalidation in organizational routines-should be a central task for health communication in the care of Crohn’s disease and other “invisible” chronic conditions.
Okuhara T, Okada H, Yokota R, Kagawa Y
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