IBD Literature Report
Coverage: September 04, 2026 - September 11, 2026
119
Papers This Week
17
Categories
Papers by Category
Click a category to expand. Click a paper title to read its abstract.
Microbiome & Immunology (20 papers)
The Association Between Attention-Deficit Hyperactivity Disorder and Gastrointestinal Symptoms: A Systematic Review and Meta-Analysis. Journal of attention disorders | 2026-09-10
Attention-Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental condition with rising prevalence worldwide. Although alterations in the gut-brain axis have been implicated in its pathophysiology, underlying mechanisms remain unclear. An increase of gastrointestinal (GI) symptoms is well documented in autism spectrum disorder, but the extent of GI involvement in ADHD has not yet been systematically evaluated. To determine whether individuals with ADHD exhibit a higher prevalence of GI symptoms compared with neurotypical controls. Following PRISMA 2020 guidelines (PROSPERO: CRD42024602363) (Blake et al., 2024), we searched MEDLINE, Embase and APA PsycInfo (all via Ovid) up to 12 May 2026. We included primary studies involving participants of any age with a DSM- or ICD-defined ADHD diagnosis and reporting GI symptoms. Studies involving formally diagnosed organic GI disease (e.g., IBD) were excluded. Two independent reviewers conducted screening and quality appraisal using Joanna Briggs Institute (JBI) tools. Where appropriate, random-effects meta-analyses were performed for individual and composite GI symptoms. From 9,613 records, 23 studies met inclusion criteria, representing over 1.9 million participants. ADHD was associated with increased odds of every GI symptom investigated, including total GI symptoms (OR 1.48, 95% CI [1.35, 1.62]), irritable bowel syndrome (OR 1.58, 95% CI [1.39, 1.78]), constipation (OR 1.97, 95% CI [1.49, 2.61]) and encopresis (OR 4.32, 95% CI [2.50, 7.47]). ADHD is associated with a substantial increase in functional GI symptoms, distinct from organic gastrointestinal disease. Possible mechanisms include gut microbiome dysbiosis, vagal dysregulation and behavioural contributors. Future research should differentiate intrinsic biological pathways from medication-related effects to improve clinical management.
Blake S, Cannon H, Shantikumar S
Microplastics and inflammatory bowel disease: dissecting the evidence from observational links to potential causal mechanisms.Review Intestinal research | 2026-09-10
Inflammatory bowel disease (IBD) has surged globally, and environmental factors such as microplastics (MPs) have emerged as potential contributors alongside a complex interplay between altered gut microbiota and dysregulated immune response in genetically susceptible individuals. While current evidence linking MPs to intestinal inflammation remains largely associative, a causal relationship between MP exposure and IBD in humans has yet to be confirmed. Therefore, this review aims to summarize current evidence regarding the occurrence, detection, and potential pathogenic roles of MPs in IBD. Emerging evidence suggests that MPs disrupt gastrointestinal integrity and immune homeostasis through multiple pathological mechanisms. MPs physically compromise the intestinal barrier by downregulating key tight junction proteins such as ZO-1 and claudin-1, altering endocytosis, and inducing oxidative stress. Concurrently, MPs induce gut microbial dysbiosis, often reflected by a reduced Firmicutes/Bacteroidetes ratio, depletion of commensal taxa, and overgrowth of proinflammatory bacteria, including Escherichia coli, Bilophila wadsworthia, and Ruminococcus gnavus. These changes trigger proinflammatory cascades and exacerbate mucosal damage, processes that are closely linked to the pathophysiology of IBD. Current detection of MPs in stool and colon tissue samples from individuals with IBD commonly relies on a combination of microscopic (e.g., optical microscopy) and spectroscopic (e.g., Fourier-transform infrared spectroscopy or Raman spectroscopy) approaches. These approaches enable the identification and characterization of MPs within biological matrices. In summary, this review explores the potential pathogenic mechanisms linking MPs to IBD, providing insights that support a possible causal relationship and highlighting a novel, underexplored environmental factor in disease onset and progression.
Soong WS, Gew LT, Chew J, Mokhtar NM, See HH, Raja Ali RA
Inflammatory Bowel Disease and Interleukin-17 Inhibitors in Hidradenitis Suppurativa: A Systematic Review and Meta-Analysis. JAMA dermatology | 2026-09-09
Interleukin (IL)-17 inhibitors have emerged as effective therapies for moderate to severe hidradenitis suppurativa (HS), but concerns remain regarding their potential association with inflammatory bowel disease (IBD). It is known that there is an increased risk of IBD in HS populations, but it remains unclear whether IL-17 inhibition increases the IBD risk or unmasks underlying disease. To evaluate the incidence of IBD in patients with HS treated with IL-17 inhibitors and to compare IBD event rates between treatment and placebo groups. PubMed, Embase, and the Cochrane CENTRAL were searched from inception through November 2025. Randomized clinical trials (RCTs), nonrandomized studies, and case reports reporting IBD outcomes in patients with HS treated with IL-17 inhibitors were included. Of 1467 records identified, 24 studies met inclusion criteria (10 RCTs, 11 nonrandomized studies, and 3 case reports). Extracted variables included study design, IL-17 inhibitor, study duration, dosing regimen, sample size, patient age, sex, baseline personal or family history of IBD, new-onset IBD, relapse of preexisting IBD, IBD subtype and clinical features, and time to IBD onset. Incidence of IBD event, defined as new-onset or worsening Crohn disease or ulcerative colitis during IL-17 inhibitor treatment in a patient with HS. For RCTs, pooled risk differences were calculated using a common effects Mantel-Haenszel model. For nonrandomized studies, a single group meta-analysis of proportions was performed to estimate pooled IBD incidence. Case reports were synthesized qualitatively. Across 10 RCTs, new-onset IBD occurred in 6 of 2572 patients treated with IL-17 inhibitors (0.23%) and in 0 of 1066 patients treated with placebo through week 16. There was no significant difference between groups (risk difference, 0.002; 95% CI, -0.003 to 0.007). In nonrandomized studies, 7 new-onset IBD events occurred among 469 patients (crude incidence, 1.49%), with a pooled incidence of 3.90% (95% CI, 2.30%-6.50%). Across randomized trials, long-term extension studies, and nonrandomized studies, 17 new-onset cases and 4 IBD flares were reported. In this systematic review and meta-analysis, IBD events were rare. No significant increase in IBD risk was observed with IL-17 inhibitors, although low event rates and inconsistent reporting limited interpretation.
Cutrona M, Jolkovsky EL, Romanelli S, O’Hagan R, Cices A
Preventive intervention with prebiotic resistant maltodextrin mitigates dextran sulfate sodium-induced colitis in female mice. Bioscience, biotechnology, and biochemistry | 2026-09-08
Ulcerative colitis (UC), an inflammatory bowel disease with a rising global prevalence, may be alleviated by short-chain fatty acids (SCFAs) derived from dietary fiber fermentation. Additionally, preventive fiber intake, rather than therapeutic, reportedly attenuates clinical and inflammatory markers of experimental colitis. To investigate the effects of preventive intake of resistant maltodextrin (RMD), a soluble dietary fiber, on colitis, female C57BL/6 mice received 6% RMD for 28 days before dextran sulfate sodium (DSS) administration. RMD mitigated colitis, as evaluated by reducing disease activity index (DAI), body weight loss, colon shortening. It increased SCFAs, particularly butyrate, before DSS treatment, with butyrate showing a negative correlation trend with DAI and a positive correlation with colon length. RMD tended to increase Fusicatenibacter saccharivorans, known to decrease in active UC, after DSS treatment, which was negatively correlated with DAI. Taken together, preventive RMD intake may attenuate experimental colitis, possibly through increased butyrate and F. saccharivorans.
Yamazaki K, Kanasaki A, Kitagawa M, Sone Y, Kishimoto Y
Structural mechanisms for ATP-mediated inhibition of human NLRP6 inflammasome. Nature structural & molecular biology | 2026-09-08
Inflammasomes ignite innate immune defense in response to infectious pathogens and noninfectious dangers, primarily through sensors composed of nucleotide-binding domain (NBD), leucine-rich repeat (LRR)-containing (NLR) family proteins. NLRP6 is an inflammasome sensor that plays critical roles in regulating intestinal inflammation, and its overactivation is linked to autoinflammatory diseases such as inflammatory bowel disease. However, how NLRP6 is maintained in an inhibited structure is unknown. Here we report two cryogenic-electron microscopy structures of human NLRP6 monomer in the adenosine-5’-triphosphate (ATP)/NBD-bound (twisted conformation) and unbound (extended conformation) states. The ATP-binding event connects and compacts the NACHT subdomains and the LRR domain, thus maintaining NLRP6 in an inhibitory conformation. NBD interacts directly with helical domain 1, winged-helix domain and helical domain 2, further contributing to the autoinhibition. Disruption of ATP binding and NBD interactions unleashes the NLRP6 inflammasome activation in the cellular study. The structural comparison between twisted and extended conformations reveals that the rearrangement of an NLRP6-specific acidic loop modulates NLRP6 activity. Although ATP-binding of NLRP6 and MCC950 (a potent NLRP3 inhibitor)-binding of NLRP3 share a similar interaction location in the structures, MCC950 does not inhibit NLRP6 in cells. Together, our data reveal the ATP-mediated cooperative inhibition mechanism of NLRP6 and provide insight into the therapeutic intervention of NLRP6-related autoinflammatory disorders.
Cui Z, Sheng Q, Son M, Goo YA, Shen C
A functional immune-based platform for donor-recipient matching in faecal microbiota transplantation for inflammatory bowel disease.★ EBioMedicine | 2026-09-07
Faecal microbiota transplantation (FMT) shows variable efficacy in inflammatory bowel disease (IBD), and current donor selection strategies rely primarily on microbiome characteristics, while host immune responses to donor microbiota remain largely unexplored. Here, we investigated whether recipient-specific immune responses to donor microbiota could be leveraged to develop a personalised donor-recipient matching strategy for FMT in IBD. We developed a proof-of-concept (POC) assay, termed Gut Microbiota-Leukocyte Reaction (GMLR), to assess immune compatibility between donor microbiota and recipients with IBD. Lamina propria mononuclear cells isolated from intestinal biopsies were exposed ex vivo to microbiota from healthy donors, and cytokines relevant to IBD pathophysiology were measured. Donor microbiota clustered into distinct groups associated with differential immune signatures, including significant IL-22 induction (p = 0.033), whereas IL-17 showed a non-significant trend toward reduction (p = 0.054) that was not consistently observed across immune cell subsets. However, immune responses were highly individualised across recipients, with substantial inter-patient variability. Based on these responses, we developed an algorithm to generate donor-recipient compatibility scores, providing a framework to prioritise potential donor-recipient pairs. Our findings suggest that donor-recipient immune compatibility is highly personalised and may represent a key determinant of FMT efficacy, challenging the “super-donor” paradigm. This ex vivo proof-of-concept platform may help prioritise donor-recipient pairs and should be prospectively validated against clinical FMT outcomes. This work was supported by the Italian Ministry of Health, Associazione Italiana per la Ricerca sul Cancro (AIRC), the European Union-NextGeneration EU (HEAL ITALIA project), and the Italian Ministry of Education and Research (MUR).
Amoroso C, Strati F, Maragno P, Caridi B, Noviello D, Gilodi M, Muià M, Frazzini S, Perillo F, Vecchi M
β-Glucan alleviates colitis by remodeling the colonic microenvironment and promoting interleukin-33-driven active eosinophil differentiation. Molecular immunology | 2026-09-07
Eosinophils play an essential role in intestinal homeostasis, yet the mechanisms governing their functions in intestine remain poorly defined. β-Glucan, an immunomodulator, has been shown to alleviate colitis, but whether it acts through eosinophils and the underlying mechanisms remains unclear. Here we show that β-Glucan pretreatment significantly attenuated dextran sulfate sodium (DSS)‑induced colitis in wild-type mice but not in eosinophil-deficient mice, indicating an eosinophil-dependent protective effect. β‑Glucan increased the frequency and absolute number of colonic active eosinophils (A-Eos), which correlated with reduced disease severity. Mechanistically, β‑glucan upregulated interleukin-33 (IL‑33) expression in colon tissues. Colon conditioned medium (CM) from β‑glucan‑treated mice directly promoted the differentiation of bone marrow‑derived eosinophils (BM-Eos) into CD80⁺PD‑L1⁺ A‑Eos ex vivo, and this effect was completely reversed by IL-33 neutralization. Our findings identify a novel β-glucan-IL-33-A-Eos axis and provide a mechanistic basis for using β-glucan as an immunomodulatory strategy to prevent inflammatory bowel disease (IBD).
Zhou J, Luo D, Hu S, Zhu H, Li Z, Cui L, Yu Z, Cao X, Wang C
Depleting luminal cysteine with engineered bacteroides vulgatus alleviates experimental colitis by suppressing Th17 differentiation through an ATF6-dependent mechanism. Inflammation research : official journal of the European Histamine Research Society … [et al.] | 2026-09-05
Ulcerative colitis (UC) is a chronic inflammatory bowel disease driven by dysregulated immune responses, particularly the aberrant activation of T helper 17 (Th17) cells. While microbiome-based therapies show promise, wild-type probiotics often lack specific mechanisms to target the metabolic and immunological drivers of inflammation. In this study, we engineered a cysteine-auxotrophic strain of Bacteroides vulgatus (BV1608) by chromosomally integrating the E. coli cyuP gene to enhance cysteine uptake. We evaluated its colonization capability, safety, and therapeutic efficacy in dextran sulfate sodium (DSS)-induced acute and chronic colitis murine models. BV1608 exhibited superior colonization and cysteine assimilation compared to the wild-type strain. Oral administration of BV1608 significantly alleviated colitis symptoms, reduced pro-inflammatory cytokines, and restored intestinal barrier integrity. Mechanistically, BV1608 created a localized cysteine-restricted microenvironment in the gut and suppressed pathogenic Th17 differentiation. Under cystine-restricted conditions, ATF6 was activated in CD4⁺ T cells, and its inhibition partially restored IL-17A⁺ CD4⁺ T cell differentiation, indicating a functional role for ATF6. Meanwhile, cystine restriction was associated with increased BATF2 expression and enhanced ATF6 binding at the BATF2 promoter, suggesting BATF2 as a potential downstream node. Our findings demonstrate that metabolically engineered B. vulgatus BV1608 ameliorates colitis by coupling microbial cysteine sequestration with host immune modulation via the ATF6-dependent suppression of Th17 differentiation, while implicating BATF2-associated transcriptional regulation as a potential downstream mechanism. This study provides a novel synbiotic strategy for treating UC by targeting the immunometabolic interface.
Wang J, Tian ZX, Chen S, Chen GY, Wang YP, Wang P
Effects of paraprobiotic Lactobacillus acidophilus LA-5 on PANoptosis, oxidative stress and inflammation in acetic acid-induced ulcerative colitis. Journal of the science of food and agriculture | 2026-09-04
Ulcerative colitis (UC) is a relapsing inflammatory bowel disease characterised by oxidative stress, inflammation and regulated cell death of the colonic mucosa. Because live probiotics may cause bacteraemia and sepsis in immunocompromised hosts, non-viable (paraprobiotic) alternatives have attracted interest. This study evaluated the antioxidant, anti-inflammatory and PANoptosis-regulating effects of a heat-inactivated paraprobiotic derived from Lactobacillus acidophilus LA-5 in acetic acid (AA)-induced experimental UC, compared to the live probiotic. Forty female Balb/c mice were assigned to four groups (n = 10): healthy control, AA colitis, live LA-5 (AA-PRO) and heat-inactivated paraprobiotic (AA-PARA). Colitis was induced by intrarectal administration of 4% acetic acid, and treatments were given by oral gavage for 7 days. Disease activity, colon histopathology, oxidant/antioxidant biomarkers, serum cytokines, PANoptosis-related proteins (western blot) and caecal short-chain fatty acids were assessed. AA increased the disease activity index, shortened the colon and induced splenomegaly, histopathological damage, oxidative stress and a systemic cytokine surge. Both treatments limited these changes; the paraprobiotic preserved colon length, reversed splenomegaly and regulated interleukin (IL)-6/IL-10 more effectively than the live probiotic (P < 0.05). All elevated PANoptosis markers (NLRP3, c-GSDMD, c-IL-1β, p-RIPK3, p-MLKL, c-caspase-3, c-GSDME and ZBP1) were suppressed by both treatments. ZBP1 was suppressed significantly more by the paraprobiotic (P < 0.05), which also increased butyric and valeric acid. The L. acidophilus LA-5 paraprobiotic exerts protective effects at least equivalent to the live probiotic, supporting its potential as a safe therapeutic candidate for UC. © 2026 The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Yavaş A, Özkıran E, Akan E
Lactiplantibacillus plantarum BF_15 Confers Protection Against Ulcerative Colitis by Orchestrating Gut Microbiota-Barrier-Immune Triad Homeostasis. Food science & nutrition | 2026-09-04
Ulcerative colitis (UC) is a prevalent chronic inflammatory bowel disease globally, driven mainly by immune dysregulation and gut microbiota dysbiosis. This study focused on Lactiplantibacillus plantarum BF_15, an infant-derived strain with potential to alleviate UC. Four experimental groups were established, including the control group, DSS group, BF_15 group, and LGG group. Probiotics were administrated at a dosage of 1 × 109 CFU/mL and 0.1 mL/10 g body weight (BW) for 21 days. The therapeutic effects and mechanisms of BF_15 against UC were explored based on physiological indicators, gut microbiota, and tandem mass tag (TMT)-based quantitative proteomics. The results showed that BF_15 intervention significantly reduced the disease activity index (DAI) from 3.00 ± 0.50 to 1.16 ± 0.36 (p < 0.05) and mitigated UC-related symptoms including body weight loss and colon shortening, with colon length restored from 4.43 ± 0.32 cm to 5.41 ± 0.26 cm (p < 0.05). Meanwhile, BF_15 downregulated the levels of pro-inflammatory factors such as interleukin IL-6 and IL-17A, and upregulated the levels of IL-10 (from 565.92 ± 79.40 pg/mL to 656.84 ± 66.01 pg/mL) and secretory immunoglobulin A (SIgA, from 9.75 ± 1.29 μg/mL to 12.79 ± 1.77 μg/mL) (p < 0.05), with a therapeutic effect comparable to that of LGG. Further, gut microbiota analysis demonstrated that BF_15 restored the relative abundance of Bacteroidetes (from 28.02% to 30.85%) and regulated gut microbiota homeostasis. Finally, TMT-based proteomic analysis indicated that BF_15 regulated 528 differentially expressed proteins (DEPs) and exhibited a superior regulatory effect on the antigen presentation and processing (APC) pathway compared with LGG. The above findings provide potential novel therapeutic targets and probiotic strain resources for the treatment of UC.
Zhang N, Liu H, Li D, Li C, Ge X, Kang H, Wang M, Tian H, Miao X
Cyanidin-3-O-glucoside ameliorates DSS-induced colitis in mice by modulating the PI3K-Akt pathway and preserving intestinal barrier function. Food & function | 2026-09-04
Anthocyanins, naturally occurring pigments in fruits and vegetables, have gained attention for their potential health benefits, including anti-inflammatory and gut-protective properties. In this study, we investigated the protective effects and underlying mechanisms of cyanidin-3-O-glucoside (C3G), a major dietary anthocyanin, in a dextran sulfate sodium (DSS)-induced murine model of inflammatory bowel disease (IBD). Oral administration of C3G significantly alleviated disease activity, attenuated body weight loss, reduced colon shortening, and suppressed systemic and colonic inflammation. C3G treatment restored intestinal barrier integrity by upregulating mucin 2 (MUC2) and key tight junction proteins, including occludin, claudin-1, and ZO-1. Integrated transcriptomic and network pharmacology analyses identified the PI3K-Akt signaling pathway and apoptosis as key targets of C3G. Experimental validation showed that C3G reduced TUNEL-positive cells in the colon and modulated apoptosis-related proteins by increasing Bcl-2 expression and decreasing cleaved caspase-3 levels. These findings indicate that C3G ameliorates experimental colitis, potentially through modulation of the PI3K-Akt pathway and suppression of epithelial apoptosis, supporting its potential as a functional food component for intestinal health.
Du G, Li J, Xu Y, Fozi V, Mehanni AE, El-Shemy HA, Nejad Ebrahimi S, Chen W
Probiotic-Derived Extracellular Vesicles as Potential Nano-Immunotherapeutic Platforms in IBD: A Clinician’s Perspective.Review International journal of nanomedicine | 2026-09-03
Inflammatory bowel disease (IBD) is a chronic, relapsing inflammatory disorder driven by complex interactions. Despite therapeutic advances, achieving sustained remission remains difficult, underscoring the need for safer and more durable treatment strategies. Increasing evidence highlights the pivotal role of the gut microbiota in IBD pathogenesis, prompting growing interest in microbiome-based interventions. Probiotic-derived extracellular vesicles (probiotic-derived EVs), a subset of bacterial EVs (BEVs), have emerged as promising cell-free mediators of host-microbe communication. These nanoscale vesicles can deliver bioactive cargo, modulate immune responses, and influence epithelial barrier function, thereby offering a potential strategy to regulate intestinal homeostasis while potentially avoiding some limitations associated with live microbial therapies. This review provides a comprehensive overview of probiotic-derived EVs, including their biogenesis, classification, and molecular composition. It further examines their biological functions and mechanisms of action in IBD, with a focus on barrier regulation, immune modulation, and microbial homeostasis. Recent advances in engineering strategies to enhance therapeutic efficacy are also summarized. Key challenges for clinical translation, including standardization, safety concerns, and limited clinical validation despite promising preclinical findings, are discussed. Together, these mechanistic and translational perspectives help delineate the current evidence, remaining limitations, and future directions regarding the development of probiotic-derived EVs as nanotherapeutic platforms for IBD.
Jeon HJ, Choe AR, Kim SE
Speedy delivery: EV-derived fungal antigens establish oral-gut Th17 crosstalk.Comment Immunity | 2026-09
Candida albicans induces Th17 cells, but their origins remain unresolved. In this issue of Immunity, Martini et al. show that the mouth is a reservoir for fungal Th17 cells that adopt pathogenic signatures in the gut during Crohn’s disease.
E Konkel J, Gaffen SL
Traditional Chinese Medicine-derived berberine-loaded herbzyme ameliorates ulcerative colitis by regulating IL10 and TMAO. Materials today. Bio | 2026-08-27
Ulcerative colitis (UC) is a common inflammatory bowel disease. The traditional Chinese medicine (TCM) formula Zanglian Wan has demonstrated promising therapeutic effects in clinical practice, yet the synergistic mechanisms among its active components remain to be fully elucidated. Inspired by this formula, this study successfully constructed a novel nanocomplex, BLCDs, through the self-assembly of Sanguisorba officinalis L.-derived carbon dots (LCDs) and berberine (BBR) via electrostatic interactions and hydrogen bonding. Characterization results showed that LCDs possessed a uniform size distribution and were rich in oxygen-containing functional groups (carboxyl, hydroxyl, carbonyl) on their surface. Their SOD-like activity was dependent on these groups and was retained after BBR conjugation. In LPS-stimulated NCM460 cells, RNA-seq identified IL10 as the most significantly upregulated gene upon BLCDs treatment. Mechanistically, BLCDs promoted the phosphorylation of STAT3 (p-STAT3), which transcriptionally upregulated IL10 expression, leading to inhibition of the NLRP3 inflammasome pathway and its downstream inflammatory cytokines. In DSS-induced mouse model, BLCDs significantly ameliorated intestinal inflammation, oxidative stress, and barrier dysfunction. This therapeutic advantage was attributed to enhanced intestinal retention conferred by their larger particle size and charge switching properties. 16S rDNA sequencing indicated that BLCDs increased gut microbiota abundance and diversity, suppressed the growth of harmful bacteria such as Klebsiella, and reduced the generation of trimethylamine N-oxide (TMAO). Colorectal normal organoids (CNOs) experiments further confirmed that BLCDs reversed TMAO-induced inflammatory lesions through an IL10-dependent mechanism. Both in vitro and in vivo safety evaluations demonstrated that BLCDs possess good biocompatibility. Taken together, this study successfully constructed BLCDs nanocomplexes integrating the antioxidant activity of LCDs and the anti-inflammatory properties of BBR. By modulating p-STAT3-IL10-NLRP3 pathway and the Klebsiella-TMAO axis to ameliorate UC, this work establishes a foundation for the development of nanomedicines based on active TCM components.
Luo T, Li M, Zhang A, Wang L, Huang Q, Wang Z, Ding K
Global research trends in enteric nervous system and gut microbiota: a bibliometric analysis (2005-2025).Systematic review Frontiers in cellular and infection microbiology | 2026-08-26
The crosstalk between the enteric nervous system (ENS) and gut microbiota, along with their roles in disease, has garnered increasing scientific attention. However, a comprehensive and objective analysis of the field’s current status and evolutionary trajectory remains lacking. We retrieved and screened relevant publications from the Web of Science Core Collection and Scopus database. Bibliometric and visual analysis were performed using CiteSpace, VOSviewer, R-studio, Origin and Excel 365. A total of 759 relevant articles and reviews published from 2005 to 2025 were included. The annual publication volume exhibited a discernible three-phase growth trajectory, culminating in a peak output in recent years. Collaboration network analysis revealed the United States as the most influential country. Leading institutions, based on publication output and centrality metrics, included University College Cork (Ireland), McMaster University (Canada), the University of Melbourne (Australia) and Baylor College of Medicine (the US). Key journals publishing in this field included the International Journal of Molecular Sciences and Neurogastroenterology and Motility. Author cooperation analysis highlighted John F. Cryan (Ireland) as the most influential scholar, with his seminal review “The Microbiota-Gut-Brain Axis” being the highly cited reference. Furthermore, keywords and co-cited reference analysis revealed that current research primarily centers on specific disorders such as irritable bowel syndrome, inflammatory bowel disease, Parkinson’s disease and Alzheimer’s disease. The pivotal role of neuroinflammation and neuro-immune interactions was consistently identified as a core pathological mechanism. Importantly, modulation of the gut microbiota via probiotics and microbial metabolites like short-chain fatty acids emerged as predominant potential therapeutic targets. Research on the gut microbiota and the ENS elucidates the mechanisms and potential therapeutic directions for a spectrum of disorders, including irritable bowel syndrome, inflammatory bowel disease, Parkinson’s disease, and Alzheimer’s disease. Fostering international collaboration and interdisciplinary exchange is crucial to accelerate the translation of high-quality research into clinical applications.
Tao W, Yu Y, Huang X, Huang J, Wang N, Shangguan X, Yu R, Xiao F
Gut microbiota-derived metabolites and IL-22 signaling in inflammatory bowel disease: context-dependent regulation of mucosal repair and inflammation.Review Frontiers in immunology | 2026-08-25
Inflammatory bowel disease (IBD), comprising Crohn’s disease (CD) and ulcerative colitis (UC), arises from complex interactions among host susceptibility, microbial dysbiosis, altered metabolite profiles, and dysregulated mucosal immune responses. Interleukin-22 (IL-22), a cytokine that acts primarily on non-hematopoietic cells, contributes to epithelial antimicrobial defense, survival, and tissue repair, but may also amplify inflammation under specific chronic or co-inflammatory conditions. This review evaluates the evidence linking major microbiota-associated metabolites-including short-chain fatty acids (SCFAs), bile acids (BAs), tryptophan (Trp) -derived metabolites, and the trimethylamine (TMA)/trimethylamine N-oxide (TMAO) pathway-to IL-22 production, bioavailability, and function in IBD. Relatively direct mechanistic support is available for SCFA-mediated and Trp-Aryl hydrocarbon receptor (AhR) -dependent regulation of IL-22, whereas bile acid effects appear metabolite-, receptor-, and context-dependent. In contrast, the proposed relationship between TMA/TMAO and IL-22 is currently supported mainly by indirect evidence and should be considered an emerging hypothesis. We further incorporate IL-22-binding protein (IL-22BP) as a determinant of local IL-22 bioavailability and distinguish upstream regulation of IL-22 production from downstream signaling initiated through the epithelial IL-22R1/IL-10R2 receptor complex. Particular attention is given to canonical JAK1/TYK2-STAT3 signaling and its context-dependent interactions with NF-κB, PI3K-AKT-mTOR, and MAPK pathways. We propose that the duration and magnitude of IL-22 exposure, its cellular source, the IL-22/IL-22BP balance, epithelial target-cell state, concurrent inflammatory signals, and disease context collectively determine whether IL-22 promotes mucosal repair or contributes to inflammatory amplification. By separating established mechanisms from associative, extrapolated, and hypothesis-generating evidence, this review provides a more evidence-calibrated framework for investigating the microbiota-metabolite-IL-22 network in UC and CD.
Shi P, He X, Zhao L, Pan W, Zhou M, Zhang T
A novel Bacillus megaterium/ω-3 PUFA synbiotic attenuates colon inflammation and promotes a pro-resolving macrophage profile ex-vivo. Frontiers in immunology | 2026-08-25
Nutritional supplementation with ω-3 polyunsaturated fatty acids has shown potential benefits in inflammatory bowel disease, although clinical responses remain inconsistent. This may be partly due to the limited conversion of ω-3 PUFAs into specialized pro-resolving mediators under physiological conditions. We investigated whether fermentation of ω-3 PUFA lysine salt with Bacillus megaterium DSM 32963 enhanced its anti-inflammatory and pro-resolving activity. The resulting formulation was evaluated in ex vivo colon biopsies obtained from patients with ulcerative colitis (UC) and healthy subjects. Inflammatory cytokine expression and macrophage-associated markers were assessed using qPCR, Western blotting and immunofluorescence. The B. megaterium/ω-3 PUFA formulation modulated the inflammatory response in ulcerative colitis biopsies, reducing the expression of selected pro-inflammatory cytokines and promoting a macrophage profile associated with resolution of inflammation. These findings provide preliminary evidence that microbial conversion of ω-3 PUFAs can enhance their pro-resolving activity in human colonic tissue. This synbiotic approach may represent a promising nutritional adjunct for ulcerative colitis, although further in vivo and clinical investigations are required.
Prete V, Picone F, Abate AC, Speckmann B, Berngruber T, Iside C, Venturini E, Vecchione C, Ciacci C, Carrizzo A
Hesperetin alleviates DSS induced colitis by inhibiting TLR2/NF-κB and restoring intestinal barrier. Biochemical and biophysical research communications | 2026-08-25
The pathogenesis of ulcerative colitis (UC) is closely associated with excessive intestinal inflammation and epithelial barrier disruption. Hesperetin possesses natural anti-inflammatory properties, but its protective mechanisms remain unclear. A DSS-induced murine UC model was established. Mice were divided into normal control, DSS model, mesalazine positive control, and low- and high-dose hesperetin groups. Colon length was measured, and histopathological evaluation was performed via hematoxylin and eosin (HE) staining. Body weight, disease activity index (DAI), TLR2/NF-κB pathway, inflammatory cytokines, tight junction proteins, ER stress and autophagy markers, and MHC II antigen presentation genes (H2-aa and H2-ab) were assessed. Additionally, AB-PAS staining was used to evaluate goblet cell abundance, and serum D-lactate (D-LA) level was detected to reflect intestinal permeability and barrier function. Hesperetin attenuated body weight loss, DAI scores and colon shortening, and dose-dependently inhibited TLR2/NF-κB overactivation, downregulated pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and iNOS, while upregulating the anti-inflammatory cytokine IL-10. Hesperetin effectively restored the expression of tight junction proteins ZO-1 and occludin, reduced the elevated serum D-LA level induced by DSS, and alleviated DSS-triggered goblet cell loss confirmed by AB-PAS staining. Moreover, hesperetin suppressed aberrant expression of ATF6 and SQSTM1, and reversed the upregulation of MHC II antigen presentation genes (H2-aa and H2-ab1). The high-dose hesperetin exhibited therapeutic efficacy comparable to mesalazine. Hesperetin alleviates DSS-induced colitis through multiple pathways, representing a promising natural candidate for UC prevention and treatment.
Xianpeng W, Yuzhou L, Yu Z, Taiyu C, Hongyuan Z, Yong W, Xuegui T
Colon-targeted oral delivery of melatonin for regulating macrophage activity and intestinal barrier in ulcerative colitis. Theranostics | 2026-08-24
Despite its promising therapeutic potential, inefficient site-specific targeting and complex fabrication processes hinder the clinical translation of oral melatonin therapy for ulcerative colitis (UC). Herein, we present Melatonin-Eudragit-Thioketal polymer-based Assembly (META), a dual pH/ROS-responsive oral microsphere for precise melatonin delivery to the inflamed colon and enhanced therapeutic outcomes. META was fabricated via a scalable emulsification process using Eudragit® FS 30 D and a thioketal polymer to enable dual pH- and ROS-responsive release. Its targeting delivery and therapeutic effects were then evaluated in simulated gastrointestinal (GI) fluids, 2D cell models, intestinal organoids, and a murine colitis model. Using cell and animal models, we showed the important role of melatonin in GI health, supporting our strategy for UC treatment. META exhibited controlled melatonin release and better accumulation in the inflamed colon. The targeted delivery helped promote disease recovery by modulating macrophages and improving the intestinal barrier. META delivers melatonin precisely to the colon, which reprograms colonic macrophages and reinforces the epithelial barrier. This study offers a practical, clinically relevant approach for improving the use of endogenous therapeutic molecules in UC and other inflammatory GI diseases.
Nguyen NN, Seo Y, Nguyen TT, Phan KP, Kausar R, Jiang HL, Lee JY, Kweon S, Tung NT, Kim HS
Decoding the power of the microbiome in human health.Review Frontiers in cellular and infection microbiology | 2026-08-21
The human microbiota plays a vital role in maintaining physiological homeostasis and overall health. Microbial communities colonize distinct anatomical sites, including the gut, oral cavity, respiratory tract, and skin, where they engage in symbiotic interactions with the host. These site-specific microbial communities contribute to essential functions such as nutrient metabolism, vitamin and short-chain fatty acid (SCFA) synthesis, immune regulation, and epithelial barrier integrity. Disruption of this balance, known as dysbiosis, is increasingly linked to a wide range of diseases, including inflammatory bowel disease (IBD), obesity, diabetes, and cancer. In this review, we summarize the current understanding of the human microbiota, highlighting its role in vitamin biosynthesis, the gut-brain axis, and immune modulation. We further the role of microbiome alterations in disease pathogenesis and outline emerging microbiome-based therapeutic strategies aimed at restoring microbial homeostasis.
Kumar M, Almohannadi N, Al Khodor S
Surgery & Complications (15 papers)
Appendico-Sigmoid Fistula as a Rare Complication of Chronic or Recurrent Appendicitis: A Case Report.Case report The American journal of case reports | 2026-09-11
BACKGROUND Appendico-colic fistula is a rare condition characterized by an abnormal communication between the appendix and colon, most commonly involving the sigmoid colon (ie, appendico-sigmoid fistula) because of their close anatomical proximity. It is usually associated with chronic or recurrent appendicitis, diverticular disease, inflammatory bowel disease, or malignancy. Preoperative diagnosis is challenging due to nonspecific clinical and radiologic findings. CASE REPORT A 46-year-old woman presented with a 3-month history of lower abdominal pain, which had worsened over the preceding 15 days and was associated with vomiting. Initial contrast-enhanced computed tomography (CECT) suggested sigmoid diverticular perforation with a localized collection. Because of discordant radiologic findings, repeat CECT with rectal contrast was performed, revealing inflammatory changes involving the appendix and sigmoid colon, along with rectal contrast entering the appendiceal lumen; these observations were suggestive of an appendico-sigmoid fistula. Exploratory laparotomy demonstrated a fistulous communication between the tip of the appendix and the sigmoid colon with surrounding inflammatory adhesions. The patient underwent sigmoid colectomy with appendectomy, colorectal anastomosis, and diverting loop ileostomy. Histopathology demonstrated inflammatory changes without evidence of diverticula or malignancy. The postoperative course was uneventful, and ileostomy reversal was performed after 2 months. CONCLUSIONS Appendico-colic fistula is a rare complication of chronic or recurrent appendicitis that can mimic sigmoid diverticular perforation. Careful interpretation of imaging, particularly CECT with rectal contrast, is important for diagnosis. Surgical management should be individualized according to the underlying etiology and intraoperative findings.
Kush S, Jena SS, Yadav A, Nundy S
Short-Term Success, Long-Term Failure: Strain Turnover and Virulence Re-Emergence May Drive Relapse in Pouchitis.★ Gastroenterology | 2026-09-09
Pouchitis, de-novo small intestinal inflammation is the most common complication developing in patients with ulcerative colitis after total large bowel resection and ileal pouch-anal anastomosis (IPAA) reconstruction. While the first line treatment is antibiotics, the microbial properties underlying flare, remission, and relapse remain vague. We aimed to investigate how antibiotic treatment drives microbial shifts that underlie remission and contribute to relapse. Patients after IPAA were prospectively recruited during clinical flare (active pouchitis defined by the pouchitis disease activity index) and received a two-week course of metronidazole with either ciprofloxacin or doxycycline. Longitudinal follow up was conducted during a year. Clinical data were recorded, and fecal samples were obtained during consequent flares, recovery, and relapses. Microbial gene repertoire, strains, and resistance to antibiotics were determined. Metagenomic sequencing was integrated with whole-genome sequencing of Escherichia coli isolates, providing strain-specific virulence and antibiotic resistance profiles. Patients (n=21) recruited provided 130 samples over one-year follow-up. Both antibiotic regimens induced rapid but transient clinical improvement, reflected by a decrease in fecal calprotectin (728 to 265 μg/g, p<.05), and a marked reduction in bacterial exotoxin genes (p<.05), yet both parameters rebounded by 6 weeks post-treatment. Antibiotic resistance gene abundance significantly increased during treatment (p<.05), without expansion of resistance gene diversity, indicating that pre-existing resistant strains increased. Antibiotic-induced remission in pouchitis likely results from a temporary suppression of exotoxin-producing bacteria, enabling resistant, low-virulence strains to transiently dominate; The fact that harmful strains quickly rebound after treatment cessation highlights the need for targeted approaches to achieve sustained microbial control.
Bilinsky L, Shamay T, Reshef L, Rabinowitz K, Vider ED, Ben-Shachar A, Friedenberg A, Pauker MH, Barkan R, Yanai H
Outcomes and Complications of Shoulder Arthroplasty in Patients With Inflammatory Bowel Disease: A Large Insurance Claims Matched Cohort Analysis. Journal of the American Academy of Orthopaedic Surgeons. Global research & reviews | 2026-09-09
Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn disease, is a chronic condition that affects the gastrointestinal tract and is associated with an increased risk of osteoporosis and fractures. With shoulder arthroplasty becoming more common, especially among aging populations, this study investigates the outcomes and complications of shoulder arthroplasty in patients with IBD. A retrospective cohort study using the PearlDiver database analyzed national insurance claims data from patients aged older than 18 years who underwent primary shoulder arthroplasty between 2010 and 2020. Patients with IBD were matched with control subjects by age, sex, and comorbidities. Primary outcomes included rates of revision arthroplasty and rotator cuff repair (RCR) between 2010 and 2020, while secondary outcomes included 90-day postoperative complications, such as infections, emergency department visits, and medical complications including deep vein thrombosis, pneumonia, and IBD-associated sepsis. Statistical significance was assessed using chi-square and multivariate analysis. Of the 8114 patients, 93.9% were older than 50 and 62.7% were female. Patients with IBD had markedly higher rates of 90-day complications, including infections (OR 4.93), ED visits (OR 4.89), pneumonia (OR 6.42), and IBD-associated sepsis (OR 16.9), among others. In addition, patients with IBD were more likely to require rotator cuff repair (OR 1.38) and undergo revision procedures (OR 1.33) compared with control subjects (P-values all < 0.01). Patients with IBD undergoing shoulder arthroplasty face a higher risk of postoperative complications and revision surgeries. These findings highlight the importance of careful preoperative evaluation and tailored postoperative care for this patient group. IV.
Khazi-Syed D, Chang J, Bohn C, Hand C, Gornbein C, Singh H, Mirle V, Gamsarian V, Harkin W, Eilen H
False ileitis: appendiceal phlegmon with fistulization to the terminal ileum mimicking Crohn’s disease. Revista espanola de enfermedades digestivas | 2026-09-09
Appendiceal disease may occasionally mimic inflammatory bowel disease (IBD), particularly when inflammation involves the terminal ileum and cecum. We report a 23-year-old man presenting with right lower quadrant abdominal pain and diarrhea, whose initial imaging findings suggested inflammatory or infectious ileocolitis, with IBD remaining in the differential diagnosis. Ileocolonoscopy revealed fibrinopurulent discharge from an inflamed appendiceal orifice and a focal inflammatory lesion in an otherwise normal terminal ileum, suggestive of fistulization from an adjacent appendiceal process. Subsequent imaging and laparoscopic surgery confirmed complicated acute appendicitis with an appendiceal phlegmon involving the terminal ileum and ileal fistulization. Histopathological examination confirmed acute gangrenous appendicitis. This case highlights the potential of appendiceal disease to mimic IBD and the diagnostic value of recognizing focal ileal abnormalities associated with appendiceal inflammatory findings.
Gabarrón López C, Rocamora Ruiz S, Madrid Sánchez A, Belando Almagro J, Muñoz Almagro E, Hernández Ortuño JE, Sánchez Martínez A, Martínez Crespo JJ
Rapid growth of a giant inflammatory polyp mimicking rectal malignancy in well-controlled Crohn’s colitis: a diagnostic and therapeutic challenge. Proceedings (Baylor University. Medical Center) | 2026-09-08
Inflammatory pseudopolyps are a recognized complication of inflammatory bowel disease (IBD). However, their development in the context of well-controlled IBD is poorly understood. A 73-year-old woman with longstanding ileocolonic Crohn’s disease that had been in endoscopic and histologic remission on sulfasalazine for 8 years developed a rapidly growing, fungating, ulcerated pedunculated rectal lesion, endoscopically indistinguishable from rectal carcinoma, within 1 year of a completely normal surveillance colonoscopy. An en bloc hot snare polypectomy confirmed an inflammatory pseudopolyp on histology, with no dysplasia or malignancy. She was subsequently escalated to vedolizumab after individualized consideration of her advanced liver disease and the agent’s gut-selective mechanism, with sustained clinical improvement. This case highlights that quiescent IBD does not preclude alarming endoscopic findings, that inflammatory polyps can develop rapidly and mimic malignancy, and that even patients with apparent remission may have residual histologic disease activity. Pathologic evaluation remains indispensable, and such lesions should prompt reassessment of therapeutic adequacy. Giant inflammatory pseudopolyps can develop rapidly in Crohn’s colitis and may appear endoscopically indistinguishable from rectal carcinoma, even after recent endoscopic remission.An ulcerated, fungating, or rapidly enlarging colorectal lesion in inflammatory bowel disease requires en bloc resection or adequate sampling with histopathologic evaluation to exclude dysplasia and malignancy.Normal C-reactive protein and fecal calprotectin do not exclude focal histologic activity; persistent inflammation should prompt reassessment of treatment, with therapy individualized for comorbidities such as advanced liver disease.
Nadeem S, Zain M, Deavers M, Schiesser RL
Association of attention-deficit/hyperactivity disorder and autism with inflammatory bowel disease activity. Journal of pediatric gastroenterology and nutrition | 2026-09-08
To estimate the effect of attention deficit hyperactivity disorder (ADHD) and autism on the disease activity of inflammatory bowel disease (IBD) in pediatric and young patients. Patients diagnosed with IBD between the ages of 6 and 24 years were identified in Danish nationwide registries 1996-2022. Cumulative incidences for severe disease activity (defined as advanced therapies, oral corticosteroids, IBD-related surgery and hospitalization) were estimated and compared between patients with IBD with and without ADHD/autism. Cox regression analysis was used to calculate adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) for each of the severe events. A total of 785 patients with IBD and ADHD/autism and 6729 patients with IBD only were included. ADHD and autism were associated with a higher cumulative incidence of severe disease activity (10-year cumulative incidence: 36.2% vs. 33.7%). When investigating each severe event, ADHD and autism were associated with a higher risk of receiving advanced IBD therapies (aHR: 1.2, 95% CI: 1.0-1.3). Patients with ulcerative colitis and ADHD/autism had a higher risk for colectomy (aHR: 1.4, 95% CI: 1.0-1.8), especially those diagnosed with IBD before 18 years of age (aHR: 1.7, 95% CI: 1.1-2.6). ADHD and autism were associated with more severe IBD disease activity in pediatric and young patients. Although mainly smaller effects were observed, the findings may inform targeted efforts for patients with ADHD/autism and IBD to reduce the likelihood of severe disease activity.
Jansson S, Wewer MD, Burisch J, Fox MP, Benros ME, Rask CU, Wewer V, Malham M
Tizanidine Withdrawal Syndrome: Clinical Manifestations and Management Strategies. Case Series. Journal of pain & palliative care pharmacotherapy | 2026-09-08
Tizanidine, an imidazole derived α2 adrenergic agonist, is widely prescribed for spasticity and chronic musculoskeletal pain. Abrupt discontinuation can precipitate withdrawal syndromes characterized by sympathetic overactivity. Although pharmacologically plausible, this phenomenon is potentially underreported in clinical practice. We describe four patients with diverse comorbidities who developed acute tizanidine withdrawal. All cases were directly observed at a single tertiary care center and identified during routine inpatient clinical practice over a defined timeline. Case 1 was a 24 year old female admitted with empagliflozin induced diabetic ketoacidosis who experienced hypertensive crisis and tachycardia following abrupt cessation of chronic high dose tizanidine. Case 2 was a 29 year old female with Crohn’s disease who developed tremors, anxiety, and autonomic instability after reducing her regimen from 40 mg nightly to 16 mg daily. She had self-discontinued her last dose prior to presentation. Case 3 was a 29 year old female with recurrent pancreatitis, resistant hypertension, and an adrenal incidentaloma who presented with severe hypertension and tremors after discontinuing both tizanidine and diazepam. Symptoms began within approximately 24 h of abrupt cessation. Case 4 was a 42 year old male with asthma, hypertension, anxiety disorder, bariatric surgery, methamphetamine use, and more than ten prior admissions specifically for tizanidine withdrawal, who presented with palpitations, tremors, vomiting, and hypertensive crisis after abrupt dose reduction. In all cases, reintroduction of tizanidine followed by a structured tapering regimen resulted in clinical stabilization. These cases highlight the clinical significance of tizanidine withdrawal, its diverse presentations, and the importance of cautious tapering. Patient education on avoiding abrupt discontinuation is essential, particularly for individuals with psychiatric comorbidities or prior withdrawal episodes. Awareness of this underrecognized syndrome is critical to prevent misdiagnosis and ensure safe prescribing practices.
AlAttar E, AlRawi F, Rafique S
Vitamin C Deficiency: A Nutritional Blind Spot in Colorectal Surgery. The American surgeon | 2026-09-07
BackgroundWhile colorectal surgery quality improvement efforts and ERAS pathways emphasize operative sterility, glycemic control, and fluid optimization, perioperative micronutrient status is rarely assessed. Vitamin C is essential for collagen crosslinking, immune function, and antioxidant activity, and deficiency may plausibly impair anastomotic and wound healing. Patients undergoing colorectal surgery may be at particular risk due to baseline malnutrition, disease related malabsorption, postoperative ileus, and reduced enteral intake. The prevalence of vitamin C deficiency in this population remains poorly characterized.MethodsWe conducted a prospective observational study of adults undergoing elective major colon resections between June 2023 and May 2025. Patients taking vitamin C supplements or undergoing anorectal procedures were excluded. Plasma vitamin C levels were obtained postoperatively.ResultsFifty-one patients were included (mean age 56.8 ± 16.7 years). Most procedures were minimally invasive (84.3%). Indications included cancer (52.9%), diverticulitis (25.5%), and Crohn’s disease (13.7%). The mean plasma vitamin C concentration was 27.8 ± 16.6 μmol/L. Seven patients (13.7%) had vitamin C deficiency, and an additional 17 (33.3%) had hypovitaminosis C, yielding a total of 47.0% with low levels.ConclusionNearly half of patients undergoing elective colorectal surgery demonstrated low vitamin C levels, with 14% meeting criteria for deficiency. These findings suggest an underrecognized micronutrient vulnerability in this population. Micronutrient assessment and optimization are seldom considered in modern ERAS pathways and may be an opportunity for future quality initiatives.
Mlaver E, Galloway L, Shaffer VO, Devin CL
IBD Nurse-Led Clinical Pathways to Optimize Patient Safety in Advanced Therapies: A Narrative Review.Review Digestive diseases and sciences | 2026-09-07
The increasing complexity of advanced therapies in inflammatory bowel disease (IBD) requires structured, safe, and reproducible care pathways. Although international guidelines define standards of care, they provide limited operational guidance for implementation in routine clinical practice. This narrative review aimed to synthesize clinical, organizational, and nursing evidence on the management of advanced IBD therapies and to organize the available evidence into clinically relevant domains of specialist IBD nursing practice. A structured narrative review was conducted to synthesize clinical, organizational, and nursing evidence related to advanced IBD therapy management. Evidence from major databases and international guidelines from the European Crohn’s and Colitis Organization (ECCO), British Society of Gastroenterology (BSG), and American College of Gastroenterology (ACG) was integrated using an interpretative approach to identify key processes and translate them into clinically applicable care domains. The narrative synthesis identified seven interrelated domains of specialist IBD nursing practice: pretreatment assessment, therapy preparation, intravenous infusion management, self-administered therapy management, clinical and laboratory monitoring, critical event management, and core knowledge of biologic and small-molecule therapies. An additional complementary section addresses emerging therapies and special clinical contexts. The identified domains encompass protocol-driven safety processes, patient education, remote monitoring, and predefined escalation pathways relevant to consistent and proactive care. This narrative review provides an evidence-informed synthesis of key nursing activities across the advanced IBD therapy continuum. The identified domains highlight areas relevant to patient safety, monitoring, education, and continuity of care and may inform future development and formal evaluation of structured nurse-led clinical pathways.
Napolitano D, Privitera G, Radice S, Schiavoni E, Lorenzon G, Murgiano M, Parello S, Bezzio C, Fiorino G, Laterza L
Small bowel perforation secondary to swallowed denture impaction at an NSAID-induced ileal diaphragm.Case report Journal of surgical case reports | 2026-09-07
Diaphragm disease of the small bowel is a rare but well-documented complication of prolonged nonsteroidal anti-inflammatory drug (NSAID) use. Characterized by circumferential mucosal diaphragms, the disease often presents as small bowel obstruction but can also lead to perforation. We report a case of small bowel perforation caused by a swallowed partial denture that became lodged at an ileal diaphragm in a patient with a history of long-term NSAID use. The diagnosis was confirmed histologically following a right hemicolectomy with primary stapled anastomosis. This case highlights the importance of considering diaphragm disease in patients on chronic NSAID therapy who present with signs of bowel obstruction or perforation, even when alternative diagnoses, such as Crohn’s disease, are initially suspected.
Sira S, Webster A, Mackay C
Preoperative myopenia is associated with postoperative complications and endoscopic recurrence after ileocolic resection in Crohn’s disease. Therapeutic advances in gastroenterology | 2026-09-06
Low muscle mass is increasingly recognised in patients with Crohn’s disease, particularly among those requiring intestinal surgery. While reduced muscle mass has been associated with adverse early surgical outcomes, its relationship with postoperative endoscopic recurrence remains poorly defined. To evaluate the association between preoperative low muscle mass, postoperative complications and endoscopic recurrence after ileocolic resection for Crohn’s disease. We conducted a retrospective cohort study including consecutive adult patients with Crohn’s disease undergoing ileocolic resection between 2017 and 2024. Muscle mass was assessed on preoperative computed tomography or magnetic resonance imaging using the total psoas area index (TPAI) with sex-specific cut-offs. The primary outcome was early postoperative complications (Clavien-Dindo grade ≥II). Secondary outcomes included endoscopic recurrence, defined as Rutgeerts score ≥i2 at follow-up endoscopy (6-12 months after surgery), and clinical factors associated with low muscle mass. A total of 152 patients were included, of whom 61 (40.1%) were classified as having low muscle mass. Postoperative complications occurred in 25.7% of patients and endoscopic recurrence in 50.7% at 6-12 months. Low muscle mass was independently associated with early postoperative complications (OR 2.80, 95% CI 1.24-6.29) and with endoscopic recurrence (OR 2.20, 95% CI 1.13-4.57). Upper gastrointestinal involvement was independently associated with low muscle mass, whereas prior exposure to biologic therapy showed an inverse association. Body mass index showed only a weak correlation with imaging-based muscle mass. Preoperative low muscle mass is common in patients with Crohn’s disease undergoing ileocolic resection and was independently associated with both early postoperative complications and endoscopic recurrence. Imaging-based body composition assessment may improve perioperative risk stratification. Crohn’s disease is a long-term inflammatory condition of the digestive tract. Some patients develop loss of muscle mass, particularly when the disease is severe or longstanding. This study investigated whether low muscle mass before surgery is linked to worse outcomes after intestinal surgery for Crohn’s disease. We retrospectively studied 152 patients who underwent ileocolic resection between 2017 and 2024. Muscle mass was measured using routine computed tomography or magnetic resonance imaging scans performed before surgery. About 40% of patients were found to have low muscle mass. These patients were more likely to develop postoperative complications and were also more likely to experience disease recurrence at follow-up endoscopy within the first year after surgery. These associations remained significant after adjustment for other clinical factors. Low muscle mass was more common in patients with upper gastrointestinal involvement. Importantly, many patients with low muscle mass had a normal body weight, suggesting that body mass index alone may fail to identify patients at nutritional risk. Our findings suggest that routine assessment of muscle mass before surgery may help identify patients at higher risk and support more personalized nutritional and postoperative management strategies.
Del Gaudio A, Becherucci G, Di Vincenzo F, Di Certo TP, Cascella F, Murgiano M, Parello S, Fiaccavento F, D’Angelo FB, Coppola G
Residual drugs in the stomach? A case report.Case report Journal of medical case reports | 2026-09-05
High-density material identified in the stomach on computed tomography (CT) most commonly represents ingested drugs, oral contrast agents, or blood. Distinguishing between these is critical, as misidentifying drugs or contrast as active gastric bleeding may lead to unnecessary interventions. We report a rare cause of hyperdense gastric material on CT, other than the three etiologies mentioned above. A 25-year-old man with Crohn’s disease presented to the gastroenterology department with suspected disease recurrence. At 11:20, a gastroscopy identified an antral ulcer, bile reflux, and a duodenal stricture, through which the gastroscope (approximately 10 mm in width) was able to pass. A subsequent CT enterography performed at 13:49 revealed several round, high-density lesions within the stomach on non-contrast and contrast CT images, which appeared distinct from the surrounding gastric mucosa. While retained oral medication was initially suspected, the patient confirmed he had ingested nothing other than a 2.5% mannitol solution, taken for CT enterography preparation following the gastroscopy. To investigate the composition of these lesions, we combined artificial gastric juice, artificial bile, and 2.5% mannitol in a test tube. This combination yielded a visible precipitate. We therefore conclude that the round lesions observed on CT most likely represent this precipitated material. This case highlights a fourth etiology of high-density gastric material on CT; it is important for radiologists and clinicians to be aware of this situation to prevent misinterpretation of images.
Zhang S, Wang C, Song H, Chen Z, Xue Y, Zhang Y, Wen H
Robotic Versus Laparoscopic Ileal Pouch-Anal Anastomosis for Ulcerative Colitis: A Systematic Review and Comparative Meta-Analysis. Journal of laparoendoscopic & advanced surgical techniques. Part A | 2026-09-04
Ileal pouch-anal anastomosis (IPAA) is the standard restorative procedure for patients with ulcerative colitis requiring colectomy. Although robotic-assisted surgery has gained increasing acceptance in colorectal surgery, its role in IPAA remains uncertain. A systematic search was conducted across PubMed, Scopus, and the Cochrane Central Register of Controlled Trials up to May 2026. Pooled odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs) were calculated using random-effects models. Heterogeneity was assessed using the I2 statistic. Sensitivity analyses were conducted to analyze outcomes with moderate or substantial heterogeneity. Six comparative observational studies involving 946 patients were included; 460 underwent robotic-assisted IPAA, and 486 underwent laparoscopic IPAA. No significant differences were observed between approaches regarding anastomotic leak (OR: 0.69; 95% CI: 0.37 to 1.28; P = .234), bleeding (OR: 0.59; 95% CI: 0.21 to 1.64; P = .309), Clavien-Dindo grade III or higher complications (OR: 1.17; 95% CI: 0.57 to 2.41; P = .670), conversion to open surgery (OR: 0.46; 95% CI: 0.16 to 1.34; P = .156), postoperative ileus (OR: 1.11; 95% CI: 0.65 to 1.91; P = .705), overall morbidity (OR: 1.17; 95% CI: 0.84 to 1.63; P = .361), reoperation (OR: 1.06; 95% CI: 0.27 to 4.19; P = .933), or 30-day readmission (OR: 0.83; 95% CI: 0.59 to 1.17; P = .278). Likewise, no significant differences were identified in operative time (MD 26.3 minutes; 95% CI: -1.9 to 54.4; P = .07) or hospital stay (MD -0.5 days; 95% CI: -1.5 to 0.5; P = .34). Sensitivity analyses did not materially alter the direction or statistical significance of the pooled estimates despite moderate to high heterogeneity in selected outcomes. Available observational evidence suggests that robotic-assisted IPAA yields short-term outcomes comparable to those of laparoscopic IPAA; however, the certainty of evidence is very low, and definitive conclusions are constrained by the observational nature of the available data.
Abud TH, de Paiva MECB, Trindade MLU, Frizzo CS, Delgado LM, Theis C, Poli de Figueiredo SM, Formiga FB, Pompeu BF
Beyond class switching in multi-refractory inflammatory bowel disease: Nine case reports and review of literature.Case report World journal of gastrointestinal pharmacology and therapeutics | 2026-09
A clinically relevant subset of patients with inflammatory bowel disease (IBD) remain partial responders despite multiple advanced therapies. In this setting, reflexive class switching risks forfeiting incremental mechanistic gains, whereas a deliberate “build-on-partial-response” strategy - through dose optimization, extended induction, and, in selected cases, advanced combination therapy (ACT) [an oral Janus kinase inhibitor (iJAK) plus a biologic] - may consolidate disease control. However, real-world data supporting ACT remain limited, particularly regarding phenotype-driven selection, objective reassessment, and safety considerations. We report nine multi-refractory IBD patients [ulcerative colitis (UC), n = 5; Crohn’s disease, n = 4] managed with ACT after incomplete response to an initial advanced therapy. UC strategies included infliximab plus tofacitinib, ustekinumab plus tofacitinib, and vedolizumab combined with iJAK. Crohn’s disease cases illustrate three patterns: Add-on anti-tumor necrosis factor therapy after partial iJAK response (e.g., upadacitinib plus adalimumab in two patients with stenosing or perianal phenotypes), interleukin-23 pathway intensification combined with iJAK (guselkumab plus tofacitinib), and phenotype discordance between extraintestinal and luminal disease control. Overall, 8/9 patients (89%) achieved clinical response with improvement in biochemical markers and/or endoscopic findings; among these, 6/9 (67%) achieved documented deep remission (clinical and biochemical, with endoscopic confirmation in 5/6). One patient with severe refractory UC failed ustekinumab plus tofacitinib and infliximab rescue and proceeded to colectomy with ileal pouch construction (11%). Patients did not present any adverse event associated with therapy, only secondary to uncontrolled disease. In multi-refractory IBD, add-on ACT may convert partial response into deep remission, averting surgery in selected patients.
Soldera J, Pertile MAS, Carobin LN, Brambilla DJF, Brambilla E
Oral and upper gastrointestinal Crohn’s disease: new perspectives on pathogenesis and clinical management.Review Frontiers in cell and developmental biology | 2026-08-21
Crohn’s disease is a chronic inflammatory bowel disease that is closely associated with genetic factors, immune dysregulation and microbial imbalance. Lesions involving the oral cavity and upper gastrointestinal tract constitute a common yet clinically overlooked manifestation of this disease. This article reviews the cellular and molecular mechanisms underlying disease onset and progression, and evaluates the diagnostic performance of various noninvasive and serum biomarkers. It also summarizes multimodal diagnostic approaches and corresponding therapeutic strategies based on current clinical practice. Currently, relevant clinical trials and standardized evaluation criteria remain lacking, largely because of the limited understanding of disease pathogenesis. Therefore, high-quality basic and translational research will be essential to deepen the understanding of this disease and facilitate the development of precision diagnostic and therapeutic strategies.
Shi X, Wang B, Zhao X, Li H, Zhou T, Li B, Tian L, Yin K
Therapeutics & Mechanisms (15 papers)
Mesalazine enteric-coated tablets combined with retention enema for symptom alleviation in mild to moderate E2-type active ulcerative colitis: A retrospective comparative cohort study. Pakistan journal of pharmaceutical sciences | 2026-12
Ulcerative colitis (UC) is a chronic inflammatory bowel disease impacting quality of life. Combination oral and topical mesalazine is guideline-recommended for left-sided UC, but real-world data remain limited. This retrospective study evaluated the efficacy and safety of mesalazine enteric-coated tablets plus a retention enema in patients with mild-to-moderate E2-type (left-sided) active UC. Patients with mild to moderate E2-type active UC treated at a single center from January 2021 to December 2022 were retrospectively screened. After applying inclusion and exclusion criteria, 88 patients were included and assigned to either the study group (mesalazine enteric-coated tablets 1.0 g four times daily plus mesalazine retention enema 4.0 g once daily) or the control group (oral mesalazine enteric-coated tablets 1.0 g four times daily alone) based on clinical availability and patient preference. Treatment duration was 30 days. Outcomes included clinical efficacy (using modified local criteria and Mayo score components), symptom relief and time to improvement, endoscopic findings (Mayo Endoscopic Subscore), and adverse events. The “effective” rate was significantly higher in the study group (77.27% vs. 34.09%; OR=6.58, P<0.001). Symptom relief rate was 97.73% vs. 72.73% (OR=13.44, P=0.002). Symptom improvement times were shorter in the study group (all P<0.05). Post-treatment Mayo Endoscopic Subscore was lower in the study group (1.14±0.41 vs. 2.05±0.65; mean difference -0.91, P<0.001). Ulcer and congestion/edema incidences were lower in the study group (6.82% and 18.18% vs. 25.00% and 47.73%). Adverse events were mild and comparable between groups (13.64% vs. 11.36%, P=0.746). Mesalazine enteric-coated tablets combined with retention enema demonstrated superior efficacy compared to oral monotherapy for short-term symptom relief and mucosal healing in patients with mild to moderate E2-type active UC, with a favorable safety profile. Larger prospective studies with longer follow-up are needed to confirm these findings and evaluate long-term outcomes.
Zhang R, Wang S, Yang M, Yang C, Yang D, Zhao Y, Zhang X
Real-World Effectiveness and Safety of Upadacitinib in Patients With Crohn’s Disease-A Multicentre Prospective Study From the Italian Group for the Study of Inflammatory Bowel Diseases (IG-IBD).★ Alimentary pharmacology & therapeutics | 2026-09-10
Upadacitinib is an oral selective JAK1 inhibitor approved for moderate-to-severe Crohn’s disease (CD), but real-world prospective multicentre data in advanced therapy-experienced (AT-experienced) patients are limited. The UPGRADE-CD study evaluated its effectiveness and safety. In this prospective, multicentre, observational study across 38 Italian centres, we enrolled consecutive AT-experienced CD patients initiating upadacitinib. Effectiveness was assessed at weeks 12 and 24, including clinical response (HBI reduction ≥ 3) and remission (HBI ≤ 4), steroid-free counterparts, biomarker normalisation, resolution of extraintestinal manifestations (EIMs) and endoscopic outcomes. Safety was assessed in all patients receiving ≥ 1 dose. A total of 391 patients were included in the safety analysis and 323 in the efficacy analysis; 48% had failed more than two advanced therapies. Clinical remission reached 51.2% at Week 12 and 54.7% at Week 24 (p = 0.07). Steroid-free clinical response rose from 53.8% to 63.5% (p = 0.09). Active EIMs, present in 39.9% at baseline, resolved completely in 65.7% by Week 24. Higher baseline HBI was the strongest predictor of failure to achieve remission. Discontinuation by Week 24 was 11.3%, mainly from treatment failure (7.2%) and adverse events (3.1%). No major cardiovascular, thromboembolic events or malignancies occurred. Upadacitinib was effective and well-tolerated in AT-experienced CD, including patients with active EIMs, with induction benefit maintained through 6 months without novel safety signals.
Barberio B, D’Amico F, Laterza L, Bezzio C, Dragoni G, Viola A, Todeschini A, Principi M, Onali S, Viganò C
From triggers to interfaces: polymer-stabilized nano-co-crystals for robust mesalazine delivery in UC.Review Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences | 2026-09-10
Ulcerative colitis profoundly alters the colonic environment, challenging conventional oral drug delivery. Fluctuating luminal pH, irregular transit, mucus remodelling, oxidative stress and microbiota dysbiosis can destabilise trigger-dependent mesalazine formulations and contribute to inconsistent colonic drug exposure. This review examines the mechanistic limitations of trigger-dependent mesalazine delivery and evaluates whether increasing formulation complexity through multi-responsive systems provides sufficient benefit under the heterogeneous and unstable conditions of active ulcerative colitis. The review analyses how pathological changes in the colonic environment influence pH-, enzyme- and inflammation-responsive systems and considers polymer-stabilised nano-co-crystal interfacial engineering as a trigger-independent approach. Particular attention is given to crystal engineering and polymer-mediated regulation at the solid-liquid and drug-mucus interfaces. Trigger-dependent systems rely on pathological cues that vary spatially and temporally during active disease, which can produce variable drug release and colonic exposure. Polymer stabilisation of nano-co-crystals provides an alternative means of controlling drug performance at the formulation interface. Polymer adsorption onto high-energy nano-co-crystal surfaces can stabilise crystalline domains, moderate dissolution, suppress aggregation and recrystallisation, and maintain controlled supersaturation under changing colonic conditions. Polymer functionality may also improve interaction with inflammation-modified mucus, prolong mucosal residence and reduce luminal washout. Using mesalazine as a representative drug, this review reframes colonic delivery in ulcerative colitis as an interface-dominated problem. Polymer-stabilised nano-co-crystals offer a trigger-independent strategy in which drug performance is regulated through crystal and polymer interfaces rather than fluctuating luminal conditions, providing a rational basis for further development of disease-adaptive colonic delivery systems.
Khan A, Kumar S, Singh AR, Agarwal M, Kailasiya A, Qureshi J
Ustekinumab combined with upadacitinib promotes endoscopic healing in moderate-to-severe Crohn’s disease with anti-TNF-α failure. Revista espanola de enfermedades digestivas | 2026-09-09
Anti-tumor necrosis factor-α (TNF-α) therapy failure in moderate-to-severe Crohn’s disease (CD) represents a major clinical challenge. However, the exploration of advanced combination therapy offers a promising direction. This study compared the efficacy of ustekinumab (UST) plus upadacitinib (UPA) with either agent as monotherapy in these patients. In this multicenter, retrospective study, 110 moderate-to-severe CD patients with anti-TNF-α failure were categorized into three groups according to the treatment they received: UST + UPA 30 mg (n = 41), UST monotherapy (n = 40), or UPA 45 mg monotherapy (n = 29). The primary outcome was endoscopic remission at 12-24 weeks, with secondary outcomes including clinical remission, clinical and endoscopic response, and safety. Following 12-24 weeks of treatment, UST + UPA 30 mg demonstrated superior efficacy. The combination group achieved significantly higher rates of endoscopic remission (51.2% vs. 17.5% UST, 24.1% UPA; p = 0.0029). The clinical remission rate in the combination group (85.4%) was significantly higher than that in the UST group (37.5%, p < 0.0001) but not significantly different from that in the UPA group (75.9%, p = 0.3138). All groups exhibited improvements in disease activity scores and inflammatory bowel disease questionnaire from baseline. Treatment-related adverse events occurred in 19.5%, 2.5%, and 13.8% of patients in the combination, UST, and UPA groups, respectively, with no serious events reported. For moderate-to-severe CD patients with anti-TNF-α therapy failure, the UST combined with UPA 30 mg regimen showed superior endoscopic healing to either monotherapy, with a tolerable safety profile. These findings suggest that this combination strategy may represent an effective treatment option for such CD patients.
Liu C, Geng Q, Lu L, An P, Wang X, Shi Y, Zhang C, Liu Z, Liu P, Sun X
Construction strategies and cutting-edge advances in oral nanozyme delivery systems.Review Journal of materials chemistry. B | 2026-09-09
Oral drug delivery is recognized as one of the most promising administration routes, primarily attributed to its superior patient compliance. Nevertheless, drugs encounter multiple physiological hurdles in the gastrointestinal tract, including the gastric acid barrier, enzymatic degradation, mucus barrier, and impaired epithelial absorption, which significantly compromise their bioavailability. Recent rapid advancements in nanotechnology have offered innovative approaches to address these challenges. This review systematically summarizes and discusses the latest research progress in oral nanodrug delivery systems, with a specific focus on elaborating delivery strategies based on diverse functional materials. These strategies encompass targeted delivery systems, environment-responsive release systems, microecological regulation systems, as well as multifunctional synergistic therapy and novel material systems. While inflammatory bowel disease serves as a primary model demonstrating their therapeutic potential, these sophisticatedly designed nanosystems also exhibit promising applications in the treatment of other conditions, including cancer, metabolic disorders, and oral infections such as periodontitis. They not only efficiently surmount gastrointestinal barriers but also enable the integration of diagnosis and therapy. Finally, this review provides an outlook on the future development directions of oral nanodrugs, emphasizing aspects of rational design, clinical translation, and personalized therapy.
He Q, Kang J, Ma D, Yang Y, Zhang L
Comparative Cost-Effectiveness of Advanced Treatment Sequences for Moderately to Severely Active Ulcerative Colitis in Japan. Advances in therapy | 2026-09-08
Ulcerative colitis (UC) is a chronic immune-mediated inflammatory disease characterized by a relapsing course, substantial symptom burden, and long-term healthcare utilization. Although multiple advanced therapies (ATs) are available for patients with moderately to severely active UC, evidence to guide optimal treatment sequencing remains limited, particularly in Japan. This study evaluated the cost-effectiveness of clinically relevant AT sequences for moderately to severely active UC in Japan. A hybrid decision-tree and Markov model was developed to compare AT sequences over a lifetime horizon from the payer perspective. The model captured both induction and maintenance phases for each therapy. Efficacy and safety inputs were derived from a previously published Bayesian network meta-analysis and supplemented with Japan-specific clinical and economic data. Costs and quality-adjusted life years (QALYs) were discounted at an annual rate of 2.0%. Incremental cost-effectiveness ratios (ICERs) were calculated, and cost-effectiveness was assessed against a Japanese cost-effectiveness threshold of JPY 7,500,000 per QALY (USD 49,547 per QALY). A total of 79 treatment sequences were evaluated. First-line etrasimod followed by second-line upadacitinib yielded the greatest health benefit (17.801 QALYs). Four treatment sequences-infliximab followed by ustekinumab, infliximab followed by etrasimod, infliximab followed by upadacitinib, and etrasimod followed by upadacitinib-were located on the efficiency frontier. Compared with infliximab-ustekinumab, infliximab-etrasimod resulted in an ICER of JPY 1,095,181 (USD 7235) per QALY. In turn, infliximab-upadacitinib had an ICER of JPY 1,218,896 (USD 8052) per QALY compared with infliximab-etrasimod. Etrasimod-upadacitinib had an ICER of JPY 6,684,442 (USD 44,160) per QALY compared with infliximab-upadacitinib. All ICERs were below the Japanese cost-effectiveness threshold. Under the assumptions of this model, a treatment sequence with first-line etrasimod followed by second-line upadacitinib was identified as the most cost-effective strategy for advanced therapy-naïve patients with moderately to severely active UC in Japan.
Kamei K, Enami M, Matsuda H, Yamagami K, Dai Y, Hoshi M, Law EH, Yuasa A
Pretreatment Histopathological Features are Associated with Ustekinumab Efficacy in Ulcerative Colitis: A Retrospective Pilot Study. Digestive diseases (Basel, Switzerland) | 2026-09-07
Biologic therapy options for ulcerative colitis (UC) have increased in recent years. Although predicting treatment response may support personalized treatment strategies, the predictive value of histopathological features in UC remains unclear. This exploratory study aimed to evaluate the association between ustekinumab effectiveness and pre-treatment histopathological findings. This single-center, retrospective, observational pilot study included patients with moderate-to-severe UC who were administered ustekinumab at the Kitasato University Hospital between April 2020 and March 2024. The endpoints were the relationship between pre-treatment histopathological findings, assessed using the Geboes score, and clinical efficacy at weeks 8 and 52, stratified by prior exposure to advanced therapies. The study enrolled 33 patients. Among advanced therapy-naïve (AT-naïve) patients, responders at week 8 were significantly more likely to have low neutrophilic infiltration in the lamina propria than non-responders (66.7% vs. 0%, p = 0.03). Among advanced therapy-exposed (AT-exposed) patients, the degree of neutrophilic or eosinophilic infiltration in colonic tissue at week 8 did not differ significantly between responders and non-responders. Among AT-naïve patients, those who achieved clinical remission at week 52 tended to have mild eosinophilic infiltration in the lamina propria compared with non-responders (80.0% vs. 33.3%, p = 0.07). Among AT-exposed patients, the degree of neutrophilic or eosinophilic infiltration in colonic tissue at week 52 did not differ significantly between responders and non-responders. In moderate-to-severe UC, pre-treatment mucosal histopathological assessment may serve as a treatment response marker. This information can guide development of personalized treatment strategies.
Horii T, Ikehara H, Harada Y, Fukagawa N, Kanazawa J, Betto T, Yokoyama K, Kusano C
Association of nutritional indices with early clinical remission in patients with moderate-to-severe ulcerative colitis treated with vedolizumab. Therapeutic advances in gastroenterology | 2026-09-04
The relationship between nutritional indices and treatment response in ulcerative colitis (UC) remains poorly characterized. To assess the discriminatory ability of Geriatric Nutritional Risk Index (GNRI), Malnutrition Universal Screening Tool (MUST), and Prognostic Nutritional Index (PNI) in evaluating the clinical efficacy of vedolizumab (VDZ) in patients with moderate-to-severe UC. A retrospective multicenter study. This study enrolled moderate-to-severe UC patients receiving VDZ at three centers in northern China from 2021 to 2025. The relationship between baseline nutritional indices and clinical remission, alongside conventional biomarkers, was analyzed. Discriminatory performance was evaluated using receiver operating characteristic curves and area under the curve (AUC) analysis. A total of 184 patients were included. At week 14, multivariable logistic regression identified GNRI, PNI and MUST as factors significantly associated with clinical remission. GNRI showed the strongest correlation with clinical remission (r=0.340, p<0.001), followed by HGB (r=0.316, p<0.001), PNI (r=0.308, p<0.001), PLR (r=-0.271, p<0.001), MUST (r=-0.216, p=0.003), and NLR (r=-0.163, p=0.027). GNRI had the highest AUC (0.697), followed by HGB (0.683), PNI (0.678), Alb (0.660), PLR (0.657) and MUST (0.614). GNRI exhibited significantly greater discriminatory ability for 14-week clinical remission than Alb (p=0.018) and MUST (p=0.041). No significant differences in diagnostic accuracy were found between GNRI, HGB, PNI, PLR, and NLR (p>0.05). At week 30 and 54, multivariate analysis showed that only baseline HGB remained independently associated with remission. Patients with lower nutritional risk-as reflected by higher GNRI and PNI scores, alongside lower MUST scores-were significantly more likely to achieve clinical remission at week 14. Malnutrition is frequently observed in UC but no research in China has evaluated the discriminatory ability of Geriatric Nutritional Risk Index (GNRI), Malnutrition Universal Screening Tool (MUST), and Prognostic Nutritional Index (PNI) in relation to VDZ efficacy. This retrospective multicenter study enrolled 184 moderate-to-severe UC patients receiving VDZ. The relationship between baseline nutritional indices and remission, alongside conventional biomarkers, was analyzed. Our findings showed that patients with better nutrition (higher GNRI and PNI scores, lower MUST scores) were more likely to achieve clinical remission by week 14. Among all evaluated indices, the GNRI exhibited the strongest association with early clinical improvement. Collectively, nutritional indices were significantly associated with early clinical remission in patients with moderate-to-severe UC receiving VDZ. It suggested that improving nutritional status may enhance VDZ efficacy and clinical outcomes.
Zhang H, Wang Y, Wu J, Wang H, Min C, Meng P, Liu H, Mao T, Xu Y, Jin L
Long-term real-world effectiveness and safety of mirikizumab in ulcerative colitis: 52-Week results from an expanded international two-center retrospective cohort study. Therapeutic advances in gastroenterology | 2026-09-04
Mirikizumab, a selective interleukin-23p19 inhibitor, has demonstrated efficacy in randomized controlled trials for moderate-to-severe ulcerative colitis (UC). However, long-term real-world data remain limited, particularly in treatment-experienced populations. To evaluate the 52-week real-world effectiveness and safety of mirikizumab in a treatment-experienced UC cohort. Two-center international retrospective observational cohort study of adults with active UC initiating mirikizumab. This study expands a previously published 12-week real-world cohort from the same centers, adding patients and extending follow-up to 52 weeks. The primary outcome was clinical remission (SCCAI ≤2) at week 52 using non-responder imputation. Secondary outcomes included clinical response, corticosteroid-free remission, and drug persistence at weeks 12, 26, and 52, as well as safety. The cohort included 120 patients with prior anti-TNF, vedolizumab, and JAK inhibitor exposure in 75.8%, 75.0%, and 42.5%, respectively. Clinical response rates were 67.5%, 52.3%, and 41.3% at weeks 12, 26, and 52, with corresponding remission rates of 14.2%, 19.8%, and 28.3% (modified NRI: 35.6%). Corticosteroid-free remission at 52 weeks was 26.1%. Drug persistence at 52 weeks was 64.6% (95% CI 54.9-72.7%), without significant differences by prior biologic exposure class. Among 60 patients (50.0%) receiving extended induction, week-26 remission was lower than in standard induction recipients (10.7% vs. 29.1%; p=0.018). Adverse events occurred in 13 patients (10.8%), leading to discontinuation in 5 (4.2%). In this large treatment-experienced real-world UC cohort, mirikizumab achieved 52-week clinical remission in 28.3% and drug persistence of 64.6%, with no new safety signals identified, supporting its role across lines of therapy in UC. 1. Why was the study done?Mirikizumab has demonstrated efficacy in randomized trials for moderate-to-severe ulcerative colitis, but long-term real-world data, particularly in treatment-experienced patients, remain limited. 2. What did the researchers do? In this international two-center cohort, they retrospectively collected and analyzed a cohort of highly treatment-experienced 120 patients who started mirikizumab induction for UC. 3. What did the researchers find? At 12 weeks, about two-thirds of patients had a clinical improvement. This decreased to about half at 26 weeks and to41% at 52 weeks. However, the proportion of patients in clinical remission increased over time, from 14% at week 12 to 28% at week 52. About 65% of patients were still receiving mirikizumab after one year. This was similar regardless of which advanced treatments patients had received before. Half of the patients received an extended induction course, usually because their disease was more difficult to control. 4. What do the findings mean? These findings support mirikizumab as a relevant long-term treatment option for patients with UC, including those with complex prior biologic or small-molecule treatment histories.
Levartovsky A, Lukáš M, Abitbol CM, Vlková K, Ben-Horin S, Lukáš M, Kopylov U
Real-world efficacy and safety of upadacitinib in difficult-to-treat Crohn’s disease: a 24-week multicenter study from China. Intestinal research | 2026-09-04
Real-world evidence for upadacitinib use in strictly defined difficult-to-treat Crohn’s disease (DTT-CD), particularly in Asian populations, remains limited. Herein, we aimed to evaluate the efficacy and safety of upadacitinib in Chinese patients with DTT-CD. This multicenter, bidirectional cohort study was conducted at 8 Chinese inflammatory bowel disease centers. Patients received upadacitinib 45 mg once daily for 12 weeks induction, followed by 15 mg daily for maintenance. The coprimary endpoints were clinical remission at week 12 and week 24. Among the 151 DTT-CD patients enrolled, the clinical remission rates were 47.0% at week 12 and 62.9% at week 24, with endoscopic remission achieved in 28.1% of patients at week 24. Adverse events occurred in 42 (27.8%) during induction and in 33 (21.9%) during maintenance, with 3 serious events (venous thrombosis, perforation, and hemorrhage) reported during the maintenance phase. Notably, 2 male reproductive system-related adverse events were observed, including blue semen in 2 patients and a suspected case of paternal teratogenicity with fetal anomalies and pregnancy loss. The drug persistence at week 24 was 93.4%. Upadacitinib demonstrated robust efficacy in Chinese patients with DTT-CD, with a manageable safety profile and high treatment persistence.
Zhang Z, Zhang S, Ge W, Li Y, Chen R, Tang W, Wang Q, Fan Y, Zhou L, Tian F
“Targeted Delivery-Long-Acting Adhesion-Synergistic Treatment” Integrated Adhesive Bilayer Microgels Loaded with Costunolide for Ulcerative Colitis Therapy.★ ACS applied materials & interfaces | 2026-09-04
Oral colon-targeted drug delivery platforms are highly important for the treatment of ulcerative colitis (UC). In this study, an adhesive bilayer microgel (Cp@GTL) integrating time-lag positioning, interfacial mucoadhesive retention, and enzyme-triggered release was engineered for targeted colonic delivery. The adhesive bilayer microgels were loaded with costunolide (Cos), a natural sesquiterpene lactone exhibiting potent anti-inflammatory activity. The inner gel layer was constructed by crosslinking gelatin and low-methoxyl pectin through tannic acid and Ca2+ chelation, forming an interpenetrating network that confers colonic mucoadhesion and enzyme-responsive degradation properties. The outer shell was fabricated via polyelectrolyte complexation between anionic sodium alginate and cationic chitosan, endowing the system with resistance to gastric acid erosion through pH-responsive structural stabilization. In vitro release studies demonstrated that the microgels effectively retarded Cos release under simulated upper gastrointestinal conditions. Following oral administration in a dextran sulfate sodium (DSS)-induced UC mouse model, Cp@GTL significantly alleviated colitis symptoms, suppressed pro-inflammatory cytokine levels, and ameliorated colonic tissue damage. Furthermore, Cp@GTL exhibited prolonged colonic retention for up to 48 h with high drug accumulation at the target site, while also modulating gut microbiota composition, enhancing microbial diversity, and reducing the abundance of pathogenic bacteria, thereby synergistically contributing to the amelioration of DSS-induced colitis. This naturally derived bilayer microgel integrates time-programmed colonic positioning, interfacial mucoadhesive retention, and enzyme-triggered drug release, enabling coordinated anti-inflammatory intervention and gut microbiota regulation. It provides a promising strategy for enhancing the intestinal application of Cos in UC-associated inflammation and offers a versatile material platform and interfacial engineering approach for the targeted amelioration of intestinal inflammatory disorders.
Hu Y, Zhu S, Lu F, Huang L, Long S, Zhao J, Wang Y, Mei P, Li X, Kang L
Letter to the Editor: Can upadacitinib dose escalation redefine treatment strategies in refractory inflammatory bowel disease?Letter World journal of gastrointestinal pharmacology and therapeutics | 2026-09
Despite major advances in inflammatory bowel disease (IBD) therapeutics, secondary loss of response remains a persistent clinical challenge. Upadacitinib, a selective Janus kinase-1 inhibitor, has demonstrated efficacy in both ulcerative colitis and Crohn’s disease; however, real-world patients frequently experience declining response during maintenance therapy. In this editorial, we discuss the findings of Ellington et al, who evaluated upadacitinib dose re-escalation to 45 mg daily in patients with refractory IBD and secondary loss of response. In their retrospective single-center cohort study involving 56 heavily treatment-experienced patients, dose escalation was associated with significant improvement in abdominal pain, hematochezia, urgency, and diarrhea, along with reduced corticosteroid exposure and favorable treatment durability. Objective inflammatory markers and endoscopic outcomes improved numerically but did not achieve statistical significance. These findings highlight the growing importance of individualized therapeutic optimization in IBD management while also underscoring the need for careful patient selection, long-term safety monitoring, and prospective comparative studies. Although current evidence remains preliminary, upadacitinib dose escalation may represent a pragmatic rescue strategy for selected patients with refractory disease.
Agrawal H, Gupta N
Effect of JAK inhibitors on extraintestinal manifestations and concurrent immune-mediated inflammatory diseases in patients with inflammatory bowel disease.Multicenter study★ Journal of Crohn’s & colitis | 2026-09
Extraintestinal manifestations (EIMs) and immune-mediated inflammatory diseases (IMIDs) are common in inflammatory bowel diseases (IBD) and contribute substantially to morbidity. The aim was to evaluate the real-world effectiveness of JAK inhibitors on EIMs/IMIDs. This multicenter retrospective study included adults with ulcerative colitis (UC) or Crohn’s disease (CD) and one or more EIM/IMID initiating a JAK inhibitor (tofacitinib, upadacitinib, or filgotinib). Baseline was defined as treatment initiation; EIM/IMID and IBD activity were assessed at fixed timepoints using physician global assessment. Response rates are reported as observed, with patients discontinuing for worsening of the manifestation counted as non-responders. Logistic and Cox regression analyses identified factors associated with response and treatment discontinuation. A total of 246 patients were included; 67% had two or more prior advanced therapies. Peripheral spondyloarthritis (SpA) (48%) and axial SpA (43%) were the most prevalent EIMs/IMIDs. Peripheral SpA response rates were 82% post-induction and 74% at month 12; axial SpA response rates were 71% and 59%, respectively. Psoriasis response was observed in 65% post-induction and in 50% at month 12, and hidradenitis suppurativa response in 91% and 78%, respectively. Steroid-free clinical IBD remission was 58% at month 12, and was independently associated with peripheral SpA response (adjusted odds ratio [aOR] 4.2, 95% CI 1.2-14.7). Treatment was discontinued in 31%; factors associated with discontinuation were filgotinib use (adjusted hazard ratio [aHR] 3.0, 95% CI 1.4-6.2) and co-existing axial and peripheral SpA (aHR 2.8, 95% CI 1.5-5.1). JAK inhibitors were associated with favorable physician-assessed outcomes for EIMs/IMIDs in treatment-experienced IBD patients. Co-existing axial and peripheral SpA was associated with treatment discontinuation, suggesting a more complex phenotype.
Truyens M, Tolstoy X, Calabrese G, Cremer A, Lewandowski K, Argyriou K, Drygiannakis I, Shakweh E, Pastras P, Kani HT
Clinical trajectories after preoperative traditional Chinese medicine in biologic-refractory surgery- intended acute severe ulcerative colitis: an exploratory retrospective case series. Frontiers in immunology | 2026-08-24
Acute severe ulcerative colitis (ASUC) is a life-threatening condition, and biologic-refractory patients may ultimately require surgery. The clinical role of individualised integrative management including traditional Chinese medicine (TCM) in surgery-intended ASUC remains uncertain. This single-centre retrospective exploratory case series included 39 biologic-refractory, surgery-intended ASUC patients treated between January 2020 and June 2025. Eleven accepted adjunctive preoperative TCM and 28 did not. Five selected TCM-treated patients experienced remission after integrative management including TCM and surgery was cancelled; 6 underwent surgery and were compared descriptively with 28 non-TCM surgical patients. Baseline imbalance was summarised using absolute standardised mean differences (SMDs). Continuous postoperative outcomes were reported as Hodges-Lehmann location shifts with 95% confidence intervals (CIs), and binary outcomes as risk differences with Newcombe-Wilson 95% CIs. Clinically relevant postoperative outcomes were prioritised, whilst postoperative day (POD) 1 white blood cell count (WBC) and POD3 C-reactive protein (CRP) were retained as exploratory inflammatory markers. Important baseline imbalances were present in the surgical comparison cohort, including surgical scope, urinalysis, haemoglobin, haematocrit, albumin, platelet count, baseline WBC, and CRP. Thirty-day postoperative complications occurred in 10/28 (35.7%) non-TCM patients and 1/6 (16.7%) TCM surgical patients (risk difference -19.0 percentage points, 95% CI -42.0 to 23.4). The Hodges-Lehmann location shift was -4.00 days (95% CI -11.00 to 3.00) for length of stay, -3.17 mg/L (95% CI -6.15 to 0.48) for POD3 CRP, and -2.59 ×109/L (95% CI -6.98 to 0.76) for POD1 WBC. No 95% CI excluded the null value. In the five selected remission cases, pre-treatment Mayo endoscopic subscore (MES) was 3 and post-treatment MES was 0 or 1; surgery was cancelled, four patients subsequently received infliximab maintenance therapy, and no subsequent surgery was recorded during 27-48 months of available follow-up. This case series describes heterogeneous clinical trajectories after individualised integrative management including TCM in selected biologic-refractory, surgery-intended ASUC patients. The small non-randomised cohorts, major baseline imbalance, concomitant treatment, surgical heterogeneity, and imprecise effect estimates preclude efficacy or causal inference. The observations should be considered descriptive and hypothesis-generating.
Tian P, Chen Z, Yu X, Fang B, Chen Z, Yu K, Lu M
Advancement in Inflammation-responsive Drug Delivery System for Chronic Inflammation. Anti-inflammatory & anti-allergy agents in medicinal chemistry | 2026-08-24
Inflammation-Responsive Drug Delivery System (IR-DDS) is proposed as a novel strategy for targeted therapy of the chronic inflammation-associated diseases: inflammatory bowel disease (IBD), rheumatoid arthritis (RA), and sepsis. These smart systems take advantage of the characteristic pathological microenvironment in inflamed tissues-such as acidic pH (5-6.5), high levels of reactive oxygen species (ROS), overexpressed enzymes, including matrix metalloproteinases (MMPs), and reductive conditions from glutathione (GSH)-for drug-specific accumulation at the site of action and on-demand release. By capitalizing on stimulus-induced behaviors, such as pH-activated protonation and swelling, ROS-stimulated bond scission in thio-ketals or boronic esters, enzyme-cleavable peptide linkers, or GSH-triggered disulfides, IR-DDS have overcome drawbacks of traditional delivery systems, including low bioavailability, off-target effects, and systemic toxicity. The review discusses a variety of carrier systems, such as polymeric nanoparticles (PLGA, chitosan), liposomes, micelles, hydrogels, dendrimers, and hybrid nanocomposites that offer inherent biocompatibility, controllable degradation, and multiple functionalities for sustained delivery. This includes the use of muscle, pH-sensitive hydrogels for periodontitis, oxidation-responsive polypropylene sulfide nanoparticles for anti-inflammatory drug release in rheumatoid arthritis models, and enzyme-triggered gelatin complexes used to target inflamed tissue in IBD, which are striking examples. A sulfasalazine-loaded transdermal patch is shown for chronic inflammation assessment, with increased efficacy in preclinical animal models, such as rat colitis and mouse arthritis after localized delivery. Despite encouraging preclinical findings in lowering cytokine levels, joint swelling, and inflammation markers, clinical translation is hindered by disease heterogeneity, scalability, biocompatibility issues, and manufacturing complexity. Future perspectives: AI-guided green multi-stimuli systems and therapeutic drug delivery, and diagnostic imaging (such as fluorescence, MRI) using multifunctional nanoparticle hybrids for personalized precision therapy will most likely revolutionize the management of chronic inflammation.
Singh R, Monika, Mazumder R, Mazumder A, Singh M, Singh G
DOI: 10.2174/0118715230494175260811080008 | View on PubMed →
Biomarkers & Precision Medicine (12 papers)
Patient Perspectives to Inform Co-creation of Wearable-Derived Digital Biomarkers for Early Flare Detection and Management in IBD: A Survey-Based Study. Digestive diseases and sciences | 2026-09-10
Wearable-derived digital biomarkers represent a new frontier in remote management of inflammatory bowel disease (IBD). They may enable continuous disease surveillance and early flare detection while reducing reliance on questionnaire-based remote monitoring. However, successful implementation into clinical practice critically depends on patient acceptance and perceived relevance. To guide patient-centered digital health strategies, we aimed to investigate patient perspectives on digital biomarkers for (early) flare detection. A nationwide cross-sectional survey-based study was conducted among patients with IBD (≥ 16 years) in the Netherlands. A study-specific questionnaire was distributed through the Dutch patient organization Crohn & Colitis NL to assess acceptance, preferences, and perspectives on the use of wearable technology for flare detection. 1,080 participants were included: 72.5% women, 53.4% aged >50 years, and 28.7% current wearable users. Overall, 88% considered remote monitoring for flare detection potentially useful, and over 90% believed wearables could support this. Motivations for using wearables included flare detection, better understanding of symptoms, and health monitoring. User-friendliness, clear alerts, and time efficiency were key device preferences, and smartwatches were the preferred wearable device. Shorter disease duration (p<0.001), more frequent flares (p=0.029), younger age (p=0.016), and current wearable use (p<0.001) were identified as predictors for willingness to use wearables. Patients with IBD value wearables for flare detection and disease-monitoring. Most participants expressed willingness to use digital biomarkers and believed that wearables could support routine care. Incorporating patient preferences into digital biomarker development will likely improve patient acceptance and adherence to remote monitoring.
Godecharle E, Totté K, van den Brink WJ, Mujagić Z, Zhang J, West R, van der Horst D, Scherpenzeel MP, Scheithauer TPM, van den Broek TJ
Time-course blood transcriptome dynamics of TNF-α inhibitor therapy in a Chinese cohort with psoriasis. The Journal of investigative dermatology | 2026-09-09
Tumor necrosis factor-alpha (TNF-α) inhibitors are effective biologics for immune-mediated inflammatory diseases, including plaque psoriasis and inflammatory bowel disease (IBD). However, time-course peripheral blood transcriptomic changes during treatment remain poorly characterized. To characterize transcriptomic changes associated with TNF-α inhibitor treatment, we profiled blood transcriptomics at three time points in 86 patients with plaque psoriasis receiving TNF-α inhibitor. We identified 3,351 time-course drug-response genes (DRGs), enriched in immune signaling and cell activation pathways and expressed in psoriatic skin lesion and blood. Among them, 259 genes showed differentially expressed between at least one pair of the three sampling time points and 962 were shared between psoriasis and IBD. TNF-α inhibitor responders showed higher expression of OLIG1, LRRK1, and KSR1, and lower expression of TNFAIP3 and MPP7 than non-responders. We identified a “red” gene co-expression module negatively correlated with treatment outcome and enriched in inflammation and TNF-related pathways. High expression of TNFSF10 (top hub gene of the “red” module) was associated with poor outcome. By week 2, the red module’s co-expression pattern changed significantly in responders but not in non-responders. This study characterizes time-course peripheral blood transcriptional programs of TNF-α inhibitor therapy in plaque psoriasis.
Xia Z, Liu L, Wang T, Xue Y, Liu J, Yu D, Hu H, Chen Q, Chu X, Peng R
Beyond inflammation: the residual burden as the next target in inflammatory bowel disease.★ Nature reviews. Gastroenterology & hepatology | 2026-09-09
Abstract not available.
Barberio B, Sebastian S, Ford AC, Gros B, Armuzzi A, Magro F, Jairath V, Savarino EV
Low-dose PFNA exposure exacerbates intestinal inflammation via caspase-11-dependent noncanonical NLRP3 inflammasome activation in macrophages. Journal of advanced research | 2026-09-04
Per- and polyfluoroalkyl substances (PFASs) have been implicated in promoting the progression of intestinal inflammation. However, the specific mechanisms remain unclear. This study aimed to elucidate how PFASs exacerbate inflammatory bowel disease (IBD) progression by directly influencing macrophages, investigate the underlying molecular mechanisms, and explore potential interventions. Primary mouse peritoneal macrophages (PMs) and a chronic colitis model were utilized to investigate the impacts of three typical PFASs, perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA), on the progression of IBD to clarify the underlying mechanisms and potential interventions. Our study found that PFNA induced significant proinflammatory responses, characterized by marked upregulation of IL-1β and IL-18 under environmentally relevant concentrations. Mechanistically, PFNA activated the caspase-11-dependent noncanonical NLRP3 inflammasome, thereby inducing dose-dependent upregulation of caspase-1, N-GSDMD, IL-1β, and IL-18. Both caspase-11 knockdown and Z-VAD-FMK inhibition attenuated these inflammatory effects. Molecular docking suggested that PFNA might induce NLRP3 inflammasome activation by interacting with pro-caspase-11. In vivo, PFNA also aggravated IBD progression through the same pathway. Conversely, based on our previous study, myricetin was found to alleviate PFNA-induced inflammation by inhibiting the caspase-11/NLRP3 axis. Our study reveals a molecular axis through which PFNA exacerbates intestinal inflammation and identifies myricetin as a potential intervention for IBD associated with PFNA exposure. These findings provide insights into the mechanisms of PFNA-induced intestinal toxicity and may guide the development of strategies to mitigate PFNA-associated intestinal inflammation.
Lu K, Cui Z, Fei X, Zhang J, Fang S, Wang Y, Chen Y, Wu Y, Xia D
Compartment-specific collagen architecture in Crohn’s disease biopsies using SHG/TPE microscopy: a pilot feasibility study. Journal of histotechnology | 2026-09-04
Intestinal fibrosis in Crohn’s disease (CD) is a key determinant of stricture formation, but collagen architecture is difficult to assess on routine mucosal biopsies because of limited tissue depth and the lack of quantitative tissue-based fibrosis measures. We evaluated the feasibility of applying second harmonic generation/two-photon excitation microscopy (SHG/TPE) with qFibrosis analysis to quantify collagen microarchitecture across histologic compartments in CD biopsies. Unstained formalin-fixed paraffin-embedded endoscopic biopsies from 31 samples obtained from 20 patients with CD were analyzed using SHG/TPE imaging and qFibrosis. Regions of interest were annotated by a gastrointestinal pathologist into glands/crypts, lamina propria, muscularis mucosae, and submucosa. Quantitative morphometric parameters reflecting collagen burden, fiber/string features, and architectural organization were compared across compartments. SHG/TPE imaging with qFibrosis successfully generated compartment-level collagen morphometric data from routine FFPE biopsy tissue. Collagen content (%SHG) and aggregated collagen (%Agg) increased progressively with tissue depth, with the highest levels observed in the submucosa. In contrast, superficial compartments showed higher fiber/string-based parameters, suggesting a more dispersed collagen architecture. These findings demonstrate measurable, depth-dependent differences in collagen organization across intestinal biopsy compartments, including patterns not readily appreciable on routine histology. SHG/TPE-based qFibrosis analysis is feasible for quantitative assessment of collagen microarchitecture in routine CD biopsy specimens and identifies compartment-specific, depth-dependent collagen patterns. However, because this pilot study lacked non-IBD controls and paired histochemical validation with Sirius Red or trichrome staining, these findings should not be interpreted as disease-specific or clinically validated. These preliminary findings support further validation of SHG/TPE-based collagen morphometry as a potential tissue-level approach for studying intestinal fibrosis in larger cohorts with controls, paired histochemical validation, histologic correlation, and clinical outcomes.
Tariq R, Hatfield B, Akbary K, Yayun R, Patki T, Reddy SL, Sanyal AJ
Integrative multi-omics analyses suggest a candidate microbial metabolite-associated host gene network in ulcerative colitis. Immunologic research | 2026-09-04
Ulcerative colitis (UC) is associated with gut microbial dysbiosis, but the host molecular alterations potentially linked to microbially derived metabolites remain incompletely understood. We integrated Mendelian randomization (MR), microbial metabolite annotation, computational target prediction, colonic transcriptomics, network analysis, and machine learning. MiBioGen microbiome GWAS data were used as exposures and FinnGen Release 12 ULCERENTER as the outcome. Metabolites linked to MR-prioritized taxa were retrieved from GutMGene, and human targets were predicted using SwissTargetPrediction and SEA. UC-related genes were defined by integrating differential expression analysis and WGCNA and then intersected with predicted metabolite targets. MR prioritized one family and eight genera showing nominal genetically supported associations with UC, but none remained significant after Benjamini-Hochberg FDR correction. Three prioritized genera were linked to 15 microbe-metabolite records, corresponding to 13 unique metabolites; nine were retained for target prediction, yielding 277 unique predicted human targets. Transcriptomic analysis identified 1,530 DEGs and a 312-gene MEgrey60 module, with 273 overlapping genes, producing 1,569 unique UC-related genes. Their intersection with the 277 predicted targets yielded 47 candidate genes. Enrichment analyses highlighted mainly metabolic and lipid-related processes. Random Forest showed the highest mean AUC across the two independent external benchmarking cohorts, and SHAP prioritized EPHX1, HSD17B2, IGFBP5, and MMP10. IBDome analysis showed inflammation-associated expression differences in these genes. This study provides a genomics-informed, hypothesis-generating framework that prioritizes candidate microbe-metabolite-host relationships in UC for future experimental validation.
Yan J, Ding S
Integrating Patient-Centric Clinical Pharmacology and MID3 to Advance Biologic Development in Immune-Mediated Inflammatory Diseases.Review Clinical pharmacology and therapeutics | 2026-09-03
Advances in biologics and model-informed drug discovery and development (MID3) are transforming the treatment of immune-mediated inflammatory diseases (IMIDs). By integrating pharmacokinetics and pharmacodynamics, MID3 enables mechanism-based, patient-centered strategies to optimize therapies, strengthen benefit-risk assessment, and advance precision medicine. Innovations such as cytokine inhibitors, bispecific antibodies, antibody-drug conjugates, and mRNA therapies have expanded treatment options across dermatology, rheumatology, gastroenterology, and respiratory medicine. The rapid development of JAK- and interleukin-targeted agents underscores the shift toward individualized, mechanistically driven therapies. At ASCPT 2025, the session “Transformative Advancements in the Treatment of IMIDs: Integrating Patient-Centric Clinical Pharmacology with Translational MID3 for Biologics” brought together experts from academia, industry, and regulatory agencies and emphasized how translational MID3 and precision pharmacology are accelerating the next generation of patient-tailored biologic therapies, with case studies in inflammatory bowel disease, systemic lupus erythematosus, and rheumatology.
Ait-Oudhia S, Zhang L, Pisal DS, Cicali B
Blood Bile Acids for Inflammatory Bowel Disease Diagnosis and Disease Activity Assessment: A Metabolomics Meta-Analysis.Meta-analysis Journal of proteome research | 2026-09
Alterations in circulating bile acids (BAs) have been reported in inflammatory bowel disease (IBD), but the consistency of these changes across clinically relevant comparisons remains unclear. Our goal was to investigate systemic BA alterations in IBD using a metabolomics meta-analysis with an exploratory analysis of BA-related gene expression as a supporting context. A systematic review and meta-analysis of 28 metabolomics studies examined blood BA profiles associated with IBD, IBD diagnosis, and disease activity assessment. Univariate analysis and logistic regression modeling of two independent IBD cohorts explored the blood BA-related genes and IBD. Across 28 studies that comprised 5056 IBD patients, 1721 healthy controls, and 314 non-IBD patients, 131 BAs were reported. Eight predefined clinical comparisons were eligible for the meta-analysis. Lower secondary BA levels were consistently observed in IBD patients compared with controls, between UC and CD, and in active versus remission patients. Deoxycholic acid, glycodeoxycholic acid, and taurodeoxycholic acid were frequently decreased, whereas glycocholic acid was increased in certain comparisons. Transcriptomics analyses revealed differential expression of several BA-related genes in blood, including SLC51A, ABCB4, and ACOT8, across the comparisons. Our findings identify consistent circulating BA alterations in IBD and highlight the relevance of blood BA for future biomarker research in the diagnosis and disease activity assessment.
Thu NQ, An VT, Dat LHB, Hung TM, Nguyen HT, Long NP
NAD+ Metabolic Reprogramming Drives CD8+ T Cells Senescence and Exacerbates Ulcerative Colitis.★ Aging cell | 2026-09
While immunosenescence is increasingly implicated in chronic inflammatory disorders, its precise pathogenic contribution to ulcerative colitis (UC) remains elusive. Here, we identify senescent CD8+ T cells as a distinct pathogenic population that exacerbates colitis, demonstrating that systemic senolytic treatment significantly attenuates disease severity. Mechanistically, nicotinamide adenine dinucleotide (NAD+) metabolic dysregulation triggers mitochondrial dysfunction and cytosolic mitochondrial DNA leakage, promoting CD8+ T cell senescence through the activation of the cGAS-STING signaling pathway. Spatial transcriptomic mapping reveals that senescent CD8+ T cells are enriched within mucosal niches experiencing NAD+ metabolic dysregulation. Crucially, this senescent-metabolic signature correlates with severe disease phenotypes and predicts non-response to biologic therapies in UC patients. Collectively, our findings uncover a critical NAD+-cGAS-STING axis driving T cell senescence, establishing the clearance of senescent immune cells as a promising therapeutic strategy for UC.
Ye M, Zhou Q, Kong M, Zhao S, Lin L, Chen L, Yu J, Luo F, Liu J, Zhang J
Computational identification and experimental validation of shared diagnostic biomarkers and gene signatures across HLA-B27-associated immune-mediated diseases. Journal of translational medicine | 2026-08-29
HLA-B27 is strongly associated with a spectrum of immune-mediated diseases, including axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), inflammatory bowel disease (IBD), and acute anterior uveitis (AAU). However, the shared molecular mechanisms and cross-disease diagnostic biomarkers remain poorly defined. This study aimed to identify common gene signatures and potential diagnostic biomarkers across HLA-B27-related diseases using bioinformatics analysis and experimental validation. Gene expression datasets for axSpA, PsA, ulcerative colitis (UC), Crohn’s disease (CD), and AAU were retrieved from the Gene Expression Omnibus (GEO) database. Disease-specific diagnostic genes were identified via differential expression analysis, least absolute shrinkage and selection operator (LASSO) regression, and receiver operating characteristic (ROC) curve analysis (AUC > 0.9). Shared biomarkers were determined by intersecting differentially expressed genes (DEGs) across all five diseases. Protein-protein interaction (PPI) networks, functional enrichment analyses, and single-sample gene set enrichment analysis (ssGSEA) were performed to explore biological pathways and immune infiltration patterns. Competing endogenous RNA (ceRNA)-transcription factor (TF) regulatory networks were constructed, and potential therapeutic agents were predicted using the Drug-Gene Interaction Database (DGIdb). Finally, the expression of candidate genes was validated by RT-qPCR and Western blot in peripheral blood mononuclear cells (PBMCs) from patients with ankylosing spondylitis (AS) and UC. A total of 2485, 380, 2682, 2232, and 481 DEGs were identified for axSpA, PsA, UC, CD, and AAU, respectively, with ABCD2 being the only shared biomarker across all five diseases. Disease-specific diagnostic gene panels were established (3 genes for axSpA, 6 for PsA, 15 for UC, 9 for CD, and 4 for AAU). Two major gene clusters were uncovered: an arthritis-related cluster (LAG3, IL15, PRF1, TBX21, IL2RB) and an extra-articular disease-related cluster (IL6, FN1, F2R, HIF1A, ANGPT2). Immune infiltration profiles varied significantly across diseases. Regulatory network analysis revealed complex ceRNA-TF interactions and identified several candidate drugs. In PBMCs, ABCD2 was upregulated in AS and UC, PRF1 in AS, and FN1, IL-6, and F2R in UC. This study identifies ABCD2 as a potential cross-disease biomarker and two context-dependent key gene clusters for HLA-B27-associated immune-mediated diseases, providing exploratory candidates for future research.
Zhu X, Liang C, Xu Z, Zhao X, Shi L, He J, Liu K, Zhou P, Xie K, Jin B
The aspiration of precision glucocorticoid pharmacotherapy in immune-mediated diseases: where do we stand in integrating pharmacogenomics and biomarkers for individualized treatment?Review Frontiers in immunology | 2026-08-24
Glucocorticoids remain among the most widely prescribed immunosuppressive and anti-inflammatory agents worldwide, yet their clinical use is complicated by substantial inter-individual variability in both therapeutic response and adverse effects. Despite decades of clinical experience, glucocorticoid prescribing remains largely empirical, with limited integration of precision medicine approaches that could optimize therapeutic outcomes while minimizing toxicity. This review synthesizes current evidence on emerging precision approaches to glucocorticoid therapy across three key domains: pharmacogenomic determinants (including variants in NR3C1, FKBP5, CYP3A4/5, and ABCB1) that modulate immune cell responsiveness to glucocorticoids; pharmacokinetic variability and model-informed precision dosing strategies; and disease-specific biomarker-guided approaches across major immune-mediated conditions including respiratory diseases, rheumatologic conditions, inflammatory bowel disease, polymyalgia rheumatica, and critical illness. Genetic variants in glucocorticoid receptor signaling and drug metabolism pathways have suggested some associations with treatment response and adverse effects, although none are yet acknowledged as clinically actionable by consensus resources. Disease-specific immunological biomarkers including eosinophil counts, inflammatory cytokines, and pharmacodynamic endpoints suggest the promise of individualized dose optimization. Risk stratification for glucocorticoid-induced osteoporosis-mediated through OPG/RANKL signaling and monocyte-osteoclast crosstalk-incorporating both clinical factors and pharmacogenetic markers may facilitate targeted prevention strategies. The integration of pharmacogenomic testing, immune biomarker monitoring, and pharmacokinetic modeling represents an aspirational paradigm shift from empirical dosing to individualized immunomodulatory therapy. It should be acknowledged that, as of the time of writing, this precision framework remains largely investigational: routine clinical practice continues to rely predominantly on indication-specific regimens and empirical tapering protocols. This review is explicitly forward-looking, aiming to outline a research agenda for precision glucocorticoid therapy in immune-mediated diseases.
Colina M, Campana G
Microbial enzyme-responsive inulin nanoparticles for colon-targeted oral delivery of 5-ASA toward improved therapy of inflammatory bowel disease. Theranostics | 2026-08-24
Colon-targeted delivery of 5-aminosalicylic acid (5-ASA) offers an effective strategy for treating inflammatory bowel disease (IBD) while minimizing systemic side effects. However, conventional oral 5-ASA formulations suffer from premature drug release and poor colon specificity. To overcome these limitations, we developed a biodegradable, prebiotic, and immunomodulatory inulin nanoparticle (INP) platform enabling microbial enzyme-responsive and site-specific release of 5-ASA in the colon. INP was fabricated via a mild nanoprecipitation method and loaded with 5-ASA (5-ASA@INP). Physicochemical characteristics, drug-loading performance, and enzyme-responsive sequential release profiles under simulated gastrointestinal fluids were evaluated. Antioxidant and anti-inflammatory effects were assessed in vitro. Biodistribution of DiR-labeled INPs was analyzed to demonstrate colon-targeting efficacy. Therapeutic efficacy, inflammatory cytokine expression, Treg responses in the colon and gut-associated lymphoid tissues, and microbiota-related effects, including short-chain fatty acid (SCFA) production, were evaluated in a colitis mouse model. 5-ASA@INP showed 97.02% drug-loading efficiency. The cumulative release of 5-ASA was 7.6% in simulated gastric fluid, 18.7% in simulated intestinal fluid, and 99.2% in simulated colonic fluid. In contrast, only 35.6% of 5-ASA was released under enzyme-free simulated colonic conditions. Compared with free 5-ASA, 5-ASA@INP showed enhanced antioxidant and anti-inflammatory effects in vitro. In vivo, INPs preferentially accumulated in the colon with minimal off-target distribution. In colitic mice, 5-ASA@INP significantly attenuated body weight loss (p = 0.0067) and colon shortening (p = 0.0002). Histological analysis showed that the colonic tissue damage was minimized and the inflammation scores were reduced (p < 0.001). Treatment increased the number of FOXP3+ cells in the colonic tissue and suppressed the expression of IL-17A, TNF-α, and IL-1β. The gut microbial profile was restored toward that of the normal group and fecal SCFA levels were increased. This study demonstrates that the INP platform enables microbial enzyme-responsive, colon-targeted delivery of 5-ASA while complementarily harnessing the intrinsic prebiotic and immunomodulatory properties of inulin. This dual-function nanoplatform provides a promising strategy for efficient oral treatment of IBD.
Park H, Son P, Oh C, Oh H, Hwang JE, Kim SY, Lee J, Lee JK, Choi WI, Im HJ
Epidemiology & Outcomes (10 papers)
Long-term outcomes of top-down therapy versus a conventional step-up strategy in adults newly diagnosed with Crohn’s disease: 5-year follow-up of the PROFILE trial.★ The lancet. Gastroenterology & hepatology | 2026-09-10
The PROFILE trial previously reported better 48-week outcomes for patients with Crohn’s disease who received top-down anti-TNF treatment from diagnosis, compared with a conventional step-up strategy. Through subsequent follow-up of PROFILE participants, we aimed to assess whether the benefit of top-down treatment from diagnosis results in modification of the long-term disease course. PROFILE was a multicentre, open-label, randomised controlled trial completed in 40 hospitals in the UK, which included patients aged 16-80 years with newly diagnosed Crohn’s disease. Eligible patients were randomly assigned via a secure online platform to a top-down (infliximab plus immunomodulator) or a step-up protocolised treatment strategy for 48 weeks, after which participants reverted to local standards of care. Objective outcome data were extracted for up to 5 years after the week 48 visit, including need for Crohn’s-related abdominal surgery as the primary outcome. Data were analysed based on the original PROFILE randomisation and intention-to-treat population. Participants without long-term follow-up data were censored at the week 48 visit. Time-to-event analyses were performed using the Kaplan-Meier method and Cox proportional hazards model. The trial was registered with the ISRCTN registry, number 11808228 and is complete. Between Dec 29, 2017, and Jan 5, 2022, 483 patients were assessed for inclusion. 389 patients were enrolled and randomly assigned (three patients were excluded due to ineligibility), 193 to top-down treatment and 193 to step-up treatment. Of the 386 participants in the PROFILE primary trial, 358 (93%) had post-week 48 records available for review (182 [51%] top-down and 176 [49%] step-up). Median follow-up was approximately 5 years from randomisation (1809 days [IQR 1300-2101]), by which point 172 (89%) of 193 patients in the step-up group and 191 (99%) of 193 patients in the top-down group had received biological or immunomodulator therapy. Relating to the primary outcome, during follow-up there were 28 Crohn’s disease-related abdominal surgeries in 26 patients treated with a step-up approach versus six surgeries in six patients treated with a top-down approach. Time to surgery was shorter in the step-up group than the top-down group (adjusted hazard ratio [aHR] 5·23 [95% CI 1·99-13·76]; p=0·0008). For the secondary outcomes, incidence of Crohn’s disease-related hospital admissions was higher in patients originally managed with step-up treatment versus top-down treatment (41 [21%] of 193 patients vs 22 [11%] of 193 patients); and time to first hospital admission was shorter with step-up treatment than with top-down treatment (aHR 2·01 [95% CI 1·18-3·41], p=0·017). Progression to B2 or B3 complications was also more frequent in those originally managed with step-up treatment compared with top-down treatment (32 [17%] of 192 patients vs 13 [7%] of 193 patients); with time to disease progression being shorter in the step-up group than in the top-down group (aHR 2·46 [95% CI 1·25-4·86]; p=0·010). There was no difference in safety outcomes between groups for either serious infections (12 [6%] of 193 step-up patients and 14 [7%] of 193 top-down patients) or malignancies (five patients [3%] and three patients [2%] respectively). Early top-down anti-TNF treatment from diagnosis was associated with improved long-term outcomes at 5 years compared with step-up treatment and is suggestive of a disease-modifying effect in Crohn’s disease. Wellcome and Celltrion.
Noor NM, Sharip MT, Zheng H, Widmer B, Brezina B, Patel KV, Dowling F, Bhatti S, Alsmade N, Ahmad T
Comparative outcomes for tirzepatide versus glucagon-like peptide-1 receptor agonists in patients with inflammatory bowel disease: a national propensity matched study. Intestinal research | 2026-09-10
Evidence suggests glucagon-like peptide-1 receptor agonists (GLP-1RAs) may improve disease-specific outcomes for inflammatory bowel disease (IBD). Tirzepatide, a dual GLP-1 and glucose-dependent insulinotropic polypeptide receptor agonist, may offer additional benefits. We compared clinical and safety outcomes among patients with IBD treated with tirzepatide versus GLP-1RAs. Patients aged ≥ 18 years with IBD were identified within a retrospective multiinstitutional U.S. database who were prescribed tirzepatide or GLP-1RA between May 2022 and January 2025. Propensity score matching (1:1) was performed for demographics, comorbidities, and IBD medications. Outcomes were assessed over 18 months and included intravenous (IV) steroid use, intestinal surgery, emergency department visits, hospitalization, and a composite of IV steroids and surgery. Adverse outcomes were assessed. After matching, 3,042 patients (mean age, 54.6 years; 71.3% female) were analyzed in each cohort. Median follow-up was 540 days (interquartile range, 478-540 days) for tirzepatide versus 540 days (interquartile range, 540-540 days) for GLP-1RA. Patients taking tirzepatide had a significantly reduced risk of IV steroid use (adjusted hazard ratio [aHR], 0.81; 95% confidence interval [CI], 0.68-0.94) and composite IBD outcomes (aHR, 0.86; 95% CI, 0.73-0.97) with similar risk of hospitalization, emergency department visit and receipt of intestinal surgery. In patients with ulcerative colitis specifically, tirzepatide was similarly associated with a reduced risk of IV steroid use (aHR, 0.82; 95% CI, 0.69-0.97). Adverse outcome risks were similar. Patients with IBD prescribed tirzepatide may have lower risk of IV steroid use compared to those taking GLP-1RAs. Prospective studies are warranted to validate these results and explore underlying mechanisms.
Patel KS, Fakhoury B, Parmar K, Jahagirdar V, Sanyal AJ, Arab JP, Tariq R
Time trends of pediatric inflammatory bowel disease in Catalonia from 2011 to 2023. Population-based cohort study. Revista espanola de enfermedades digestivas | 2026-09-09
Data on temporal trends in treatment use in pediatric inflammatory bowel disease (PIBD) are limited. This study aimed to evaluate treatment trends in PIBD in Catalonia and to explore their association with outcomes, including surgery and hospitalization. We conducted a population-based cohort study including all pediatric patients (<18 years) with IBD included in the Catalan Health Surveillance System, covering a population of more than 7.5 million individuals, between 2011 and 2023 were identified. Exposure to IBD treatments was obtained from electronic dispensation records. Temporal trends in treatment use, surgical procedures, and hospitalization rates were analyzed. Correlation analyses between treatments and outcomes were performed at the population level. The use of salicylates and corticosteroids increased from 18.6% to 24.8% and from 5.2% to 12.3%, respectively. Immunosuppressive treatment increased during the early study period and subsequently declined, with similar rates at baseline and study end (28.3% vs 29.5%). Advanced therapies increased markedly from 27.0% to 41.8%, with infliximab remaining the most frequently prescribed advanced therapy. Surgical rates (ostomies and resections per 1,000 patient-years) fluctuated over time without a consistent trend (p=0.21). Rates of PIBD-related hospitalization decreased from 205.2 to 150.3 per 1,000 patient-years. Advanced therapies use in PIBD increased substantially over the study period in Catalonia. This trend coincided with a reduction in PIBD-related hospitalization rates, whereas surgical outcomes remained unchanged. This increase occurred concurrently with a reduction in hospitalization rates, whereas no statistically significant linear trend was observed for surgical outcomes.
Brunet-Mas E, Garcia D, Vela E, Comalrena C, Melcarne L, Loverdos I, Pontes C, Llovet LP, García-Sagué B, Frisancho LE
Translation and validation of the IBD-disk for assessing disability in Spanish-speaking patients with inflammatory bowel disease. Revista espanola de enfermedades digestivas | 2026-09-09
Assessment of IBD patients based on patient reported outcome measures has an increasing interest worldwide for both clinical practice and biomedical research. One of the most common and easy-to-use tools is the IBD-Disk, which assesses the disability status of IBD patients. However, there is no validated version for Spanish-speaking patients. The aim of the study is to translate and validate a Spanish version of the IBD-Disk. The original English version of the IBD-Disk was translated, linguistically and culturally validated in a Spanish speaking cohort of IBD patients from Spain and Latin America and tested in comparison with the Spanish version of the IBD-disability index (IBD-DI) after 24 weeks of follow-up. Globally, 102 patients were enrolled (52 Crohn’s Disease and 50 ulcerative colitis). Internal consistency was 0.925 [95% CI: 0.902-0.945]. Intraclass correlation coefficient was 0.956 between baseline (T0) and week 1 (T1) [95% CI: 0.936-0.970] indicating satisfactory test-retest. Correlation with IBD-DI was 0.912 [95% CI: 0.872-0.940]. Activity indices were shown to be independent factors associated with IBD-Disk. The Spanish version of the IBD-Disk shows adequate internal consistency and test-retest, and convergent validity, thus confirming its utility in controlling global health status in IBD patients.
González-Muñoza C, Giordano A, Gely C, Gordillo J, Bertoletti F, García-Planella E
Campylobacter spp. infection and subsequent clinical outcomes in patients with inflammatory bowel disease. Revista espanola de enfermedades digestivas | 2026-09-09
Campylobacter species (spp) infection has been linked to the development of inflammatory bowel disease (IBD), but its impact on the clinical course of patients with established IBD remains unclear. We conducted a single-centre retrospective cohort study including all stool samples positive for Campylobacter spp. between 2010 and 2024. Patients aged ≥14 years with IBD and microbiologically confirmed Campylobacter infection were included. Infected patients were matched 1:2 with uninfected IBD controls using propensity score matching. The primary outcome was a composite adverse clinical course within 12 months, defined as IBD-related hospitalization, treatment intensification, surgery, or death. Among 2,662 stool cultures positive for Campylobacter spp., 43 corresponded to patients with IBD ≥14 years (20 CD, 23 UC); one UC patient with prior colectomy was excluded, yielding 42 infected IBD patients. Campylobacter-positive stool cultures were more commonly identified among patients with IBD than in the general population (1.656% vs. 0.576%; RR 2.87, 95% CI 2.13-3.87; p<0.0001). However, this comparison was descriptive and cannot establish a true increased infection risk. After matching, 126 patients were analyzed. In an exploratory Cox proportional hazards model performed in the matched IBD cohort and stratified by IBD subtype, Campylobacter spp. infection was associated with shorter time to the primary composite endpoint (HR 4.49, 95% CI 1.90-10.61; p<0.001). Subgroup analyses in CD and UC showed directionally consistent findings but were limited by small event numbers and wide confidence intervals. In CD, Campylobacter infection was associated with a higher frequency of flare (25.0% vs. 5.0%; p=0.036) and treatment intensification (35% vs. 7.5%; p=0.012). In UC, infection was associated with increased risk of flare (31.8% vs. 9.1%; p=0.033), while differences in hospital admission and treatment intensification did not reach statistical significance. In this single-centre retrospective matched cohort study, microbiologically confirmed Campylobacter spp. infection in patients with established IBD was associated with subsequent IBD flare and need for treatment escalation within the first 12 months. Given the retrospective design, limited event numbers, residual confounding, and potential ascertainment bias, these findings should be considered exploratory.
Alañón P, Orti Cuerva M, Muñoz Peña M, Causse M, Benítez JM, Marín Pedrosa S, Soto Escribano P, Iglesias-Flores E, Gros B
Influence of socioeconomic development on incidence and disease phenotype in inflammatory bowel disease: a population-based incident study across 16 regions.★ Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association | 2026-09-08
The global rise in inflammatory bowel disease (IBD) parallels socio-economic development, but its influence on disease epidemiology and phenotype remains unclear. We aimed to characterise IBD incidence, clinical features, and associations with socio-economic indices across newly industrialised countries. This prospective population-based study spanned 16 regions in Africa, Asia, Latin America, and the Middle East from October 2021 for one year. Poisson regression estimated incidence rate ratios (IRR) for Human Development Index (HDI), Socio-demographic Index (SDI), subnational HDI, and urban population percentage. Mixed-effects models examined associations with disease phenotype, activity, and treatment. Of 606 incident cases (229 Crohn’s disease [CD], 348 ulcerative colitis [UC], 29 IBD-unclassified), incidence varied widely. Hong Kong had the highest crude annual incidence (IBD 7.43; CD 2.69; UC 3.44) and Vietnam the lowest (0.13; 0.04; 0.08). Urban population (per 10% increase) was associated with higher incidence of IBD (IRR 1.68), CD (1.73), and UC (1.62). HDI and SDI significantly correlated with CD (IRR 4.05 and 2.96, respectively), but not subnational HDI. Higher HDI and subnational HDI were associated with increased odds of perianal CD (adjusted OR 2.61 and 2.40). Other disease phenotype, activity, and treatment pattern were not significantly linked to any index. Higher urbanisation and development are associated with higher IBD incidence, particularly CD, but not with disease activity at diagnosis. Notably, perianal CD was more common in regions with higher HDI and subnational HDI, suggesting an association with regional socioeconomic development. These highlight the need for region-specific early diagnosis strategies.
Mak JWY, Ho AHY, Chan AKW, Miao Y, Sun Y, Dao HV, Kaibullayeva J, Paudel MS, Limsrivilai J, Wei SC
Cumulative thalidomide exposure, peripheral neuropathy, and clinical outcomes in pediatric and very early-onset inflammatory bowel disease: a retrospective cohort study. Clinics (Sao Paulo, Brazil) | 2026-09-08
Thalidomide serves as a rescue therapy for refractory pediatric Inflammatory Bowel Disease (pIBD), but its use is constrained by the risk of thalidomide-induced Peripheral Neuropathy (TiPN). The quantitative relationship between cumulative dose and TiPN, as well as the risk profile in the specific population of Very Early-Onset IBD (VEOIBD), lacks precise evaluation. We conducted a single-center, retrospective cohort study of children with IBD treated with thalidomide from 2018 to 2025. We compared cumulative thalidomide doses between TiPN and non-TiPN groups and employed ROC curve analysis to determine a predictive dose threshold. The cohort was further stratified into VEOIBD and pIBD groups to compare dynamic inflammatory marker changes and overall drug tolerability. Among 49 included patients, the incidence of TiPN was 26.5% (13/49). The cumulative thalidomide dose was significantly higher in the TiPN group (median 19.5 g vs. 8.35 g, p = 0.008). A cumulative dose threshold of > 15.38 g predicted TiPN with an AUC of 0.756 (sensitivity 0.722, specificity 0.692). While VEOIBD patients (n = 14) had a distinct disease treatment history, they experienced significantly fewer overall adverse events than pIBD patients (3/14 vs. 19/35, p = 0.04), with no significant difference in TiPN incidence. Cumulative thalidomide dose is a strong predictor of TiPN in children with IBD. Despite being a more refractory population, VEOIBD patients demonstrated better overall tolerance to thalidomide. Monitoring cumulative dose is crucial for mitigating neurotoxicity and optimizing thalidomide therapy in pIBD.
Mao J, Li P, Chen Z, Cao Z, Yang L, Li Z, Wang Z, Liang S
Reply: “Appendectomy before or after ulcerative colitis and the long-term outcomes”.Editorial★ Inflammatory bowel diseases | 2026-09-05
Declining Rates of Surgery for Nonmalignant Colorectal Polyps in the United States Over the Last Decade: A Real-World Analysis of Over 1 Million Patients. Endoscopy international open | 2026-09-01
Background Despite advancements in endoscopic resection (ER), surgery for nonmalignant colorectal polyps remains common. A prior analysis reported increasing surgical rates from 2000 to 2014. Using the TriNetX US Research Network, we aimed to compare the proportion of patients referred for ER versus surgical colectomy for nonmalignant polyps each year from 2015 to 2023. Methods We identified adults (≥18 years) diagnosed with nonmalignant colorectal polyps following colonoscopy using validated ICD-10 and CPT codes. Patients with colorectal cancer or inflammatory bowel disease were excluded. The primary outcome was incidence of ER (EMR or ESD) vs. colectomy between 2 weeks and 6 months post-colonoscopy. Secondary outcomes included 30-day adverse events (AEs) and mortality. Propensity score matching was used to compare groups. Odds ratios (ORs) were calculated for secondary outcomes. Results Of 1,060,302 patients undergoing colonoscopy from 2015 to 2023, 6,295 (0.594%, 95% CI: 0.579-0.609%) were referred for ER and 4,208 (0.397%, 95% CI: 0.385-0.409%) were referred surgery for large nonmalignant colorectal polyps detected and not resected on index colonoscopy. ER incidence rose from 0.26% (2015) to 0.67% (2023), while surgery rates declined from 0.45% to 0.35%. Post-matching, ER was associated with significantly lower 30-day mortality (0.161% vs. 1.304%; OR: 0.122) and fewer AEs, including cardiac events, thromboembolic events, pulmonary complications, sepsis, and surgical site infections. Discussion Over the past decade, ER for nonmalignant colorectal polyps increased while surgical resections declined. ER was associated with significantly lower mortality and morbidity. These findings support continued efforts to promote ER as a safer, effective alternative to surgery.
Jaber F, Salahat AJ, AlMasri MM, Obiedat K, Jaber M, Skef W, Khalaf M, Keihanian T, Jawaid S, Othman M
High prevalence of fatigue in patients with inflammatory bowel disease: association with physical activity intensity and sedentary behavior. Frontiers in public health | 2026-08-27
Fatigue is reported to be a common and disabling manifestation in patients with inflammatory bowel disease. Specialized units and nurse-led services play key roles in delivering holistic, long-term care for these patients. The aim of this study was to determine the prevalence of fatigue among inflammatory bowel disease patients attending a day hospital. The association between fatigue and physical activity was also analyzed, potentially providing clinically relevant information for nursing assessment and targeted interventions. A descriptive, cross-sectional study was performed on a sample of 422 patients (Crohn’s disease, 64.5%; colitis, 35.5%) attending the day hospital of the Son Espases University Hospital (Palma, Balearic Islands, Spain). Sociodemographic and disease characteristics, physical activity levels, and sedentary time were determined using a questionnaire. Data were analyzed using descriptive statistics. The primary statistical analyses consisted of comparisons between participants with and without fatigue and across fatigue severity levels using Student’s t-test, one-way ANOVA, or Pearson’s chi-square test, as appropriate. Most of the participants were in clinical remission (Crohn’s disease, 95%; colitis, 71.1%). The prevalence of fatigue was 70.1%, with more than half of fatigued patients reporting a mild level of fatigue. Fatigue was found to be associated with depression and anxiety, with a higher prevalence of fatigue among the participants reporting to have these disorders (p = 0.010). Fatigue was associated with lower levels of physical activity (p = 0.002), mainly lower levels of intense physical activity, and in participants with severe fatigue. The participants with fatigue reported longer daily sitting times (p = 0.005). Furthermore, fatigue was associated with taking supplements (p = 0.016) and food avoidance (p < 0.001). A high prevalence of fatigue was found among patients with inflammatory bowel disease. Exercise intensity and fatigue level were found to be key factors, with fatigue being negatively associated with participation in physical activity. Patients with fatigue, particularly those with severe fatigue, engaged in lower levels of physical activity, especially high-intensity exercise. However, walking and moderate-intensity exercise appeared to be well tolerated. Additionally, fatigue was associated with being sedentary for greater durations.
Herrera MD, Aguiló A, Tauler P, Mingorance JA, Ginard D, Puchol E, Martínez S
Quality of Life & PROs (10 papers)
Validation of a Patient-Created, Patient-Reported Experience Measure for Inflammatory Bowel Disease in the United Kingdom. Health expectations : an international journal of public participation in health care and health policy | 2026-10
Inflammatory bowel disease (IBD) significantly impacts quality of life and has high healthcare contact. Ensuring that patients are experiencing the best care is therefore essential and has been the focus of many quality improvement initiatives. To support this, in collaboration with patients, we developed a patient-reported experience measure for IBD (IBD-PREM) for use in a UK context. This article refers to the validation of this patient-developed measure to ensure it is valid and reliable. Using data from the AWARE-IBD study, 287 participants provided data between November 2021 and November 2024. The IBD-PREM as well as the IBD-Control questionnaire was collected at 3-month intervals as well as 2 weeks post baseline. Validation was completed through testing the following aspects: acceptability (response rate and missing data rates), reliability (internal consistency and test-retest reliability), validity (construct and structural validity using factor analysis) and responsiveness (ceiling/floor effects and smallest detectable difference). High response rates and low missing data demonstrated acceptability of the IBD-PREM. There was also good test-retest reliability (ICC = 0.88). Low ceiling and floor effects demonstrate suitable responsiveness as did the ability to differentiate between patients with active and inactive disease (effect size = 0.62). The confirmatory factor analysis suggested the current domain structure (three domains) is not optimum and factor loadings indicated some potentially redundant items, which is supported by the high internal consistency (α = 0.97). The patient-developed IBD-PREM is a tool that can be used as a method for assessing the healthcare experiences of IBD patients in the United Kingdom. Superior psychometric properties were found compared to measures developed through traditional researcher-led approaches suggesting the benefit of involving patients early in the methodological process. Further refinement in terms of item reduction and domain restructure should be implemented to optimise the PREM as well as external validity to other contexts. Patients and members of the public were engaged from an early stage in the development of the PREM, contributing directly to the design and content of the IBD-PREM. This article goes on to validate this patient-created measure with input from a patient representative.
Guy Z, Hind D, Totton N, Sheldon E, Ezaydi N, Bursnall M, Lobo A
A Multistep Registration Framework for Multimodal Histology Across Same and Consecutive Sections. Journal of imaging informatics in medicine | 2026-09-10
Multimodal digital pathology combines hematoxylin and eosin (H&E) staining with advanced microscopy techniques to provide complementary structural and molecular information. However, accurate registration between H&E and other modalities remains challenging, especially when images differ strongly in appearance or are acquired on nonidentical consecutive sections. We present a multistep multimodal registration workflow that combines a multiscale histogram of local main orientations (MS-HLMO), a multimodal feature-based rigid initialization, with B-spline nonrigid registration and thin-plate spline refinement. We evaluated this approach on two datasets: human intestinal inflammatory bowel disease sections imaged with nonlinear multimodal microscopy (nMM) and H&E and head and neck cancer biopsies imaged with H&E and coherent Raman scattering (CRS), including single-band stimulated Raman scattering (SRS) and multimodal CRS images on parallel frozen sections. Registration performance was quantified using landmark and boundary-based metrics. The workflow was compared with several registration approaches, including scale-invariant feature transform (SIFT), B-spline deformable registration, MS-HLMO, and VALIS. For H&E/SRS pairs, the workflow reduced the median landmark error from 0.01459 to 0.01204 and lowered the mask boundary error from 0.0482 to 0.0115 compared with MS-HLMO. For H&E/nMM pairs, it achieved the lowest boundary errors, while B-spline registration yielded the smallest landmark errors, indicating a trade-off between point accuracy and boundary alignment. Qualitative checkerboards showed that the proposed method produced more consistent multimodal alignments than SIFT and VALIS across the evaluated datasets. These results demonstrate that the proposed workflow provides robust multimodal registration for both same-section and consecutive-section histology and enables reliable transfer of annotations between H&E and advanced microscopy modalities.
Darzi F, Escobar Díaz Guerrero R, Bocklitz T
Increasing Global Burden of Inflammatory Bowel Disease and Its Attributable Anemia in Adults Aged 60 Years and Older: A Comprehensive Analysis of the Global Burden of Disease Study 2021. Journal of digestive diseases | 2026-09-09
To quantify the global burden of inflammatory bowel disease (IBD) and IBD-attributable anemia in adults aged ≥ 60 years across 204 countries and territories from 1990 to 2021 and their projected trends through 2045 based on the Global Burden of Disease (GBD) 2021 database. Data were extracted from the GBD 2021 database. Age-standardized rates (ASRs) were calculated by age, sex, region, and sociodemographic index (SDI). Joinpoint regression analysis was used to quantify temporal trends. Decomposition analysis assessed drivers of burden change. Concentration index methodology quantified socioeconomic inequalities. And Bayesian age-period-cohort (BAPC) models projected burden through 2045. Prevalent IBD cases among adults aged ≥ 60 years increased by 123% from 573 503 in 1990 to 1 278 194 in 2021, while the age-standardized prevalence rate (ASPR) remained stable. In contrast, the age-standardized incidence rate (ASIR) increased particularly among women (average annual percentage change [AAPC]: 0.31%) than in men (AAPC: 0.26%). IBD-attributable anemia affected 361 157 elder adults in 2021, with a rising ASPR in women. Mortality and disability inequalities widened, with concentration index increasing from 0.07 to 0.23 for mortality and from 0.14 to 0.25 for disability-adjusted life-years (DALYs). By 2045, prevalent cases are projected to reach 2 161 387. Burdens of IBD and IBD-attributable anemia in adults aged ≥ 60 years have increased substantially, driven predominantly by the demographic expansion of this population. The ASIR continues to rise, particularly among women and in lower-SDI regions, together with widening socioeconomic inequalities, highlighting the need for early diagnosis, anemia screening, frailty assessment, and equitable resource allocation.
Wang JQ, Yan RC, Hu YY, Chen LY, Chen SJ, Liu H
Climate classification, sociodemographic development, and the burden of inflammatory bowel disease in tropical countries. Tropical medicine and health | 2026-09-07
Geographic definitions of the tropics may obscure substantial climatic heterogeneity. Climate classification provides a more ecologically meaningful framework for evaluating inflammatory bowel disease (IBD) in tropical settings. However, few studies have examined tropical IBD burden using an integrated framework that combines climate classification, sociodemographic development, decomposition analysis, frontier analysis, and long-term forecasting. We analyzed 1990-2023 estimates of IBD incidence, prevalence, mortality, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) from the Global Burden of Disease Study 2023. Climatic heterogeneity was characterized using the Koppen-Geiger climate classification. Temporal trends were evaluated with estimated annual percentage change (EAPC), and associations with tropical climate proportion and the sociodemographic index (SDI) were examined using Spearman rank correlation. Das Gupta decomposition quantified the contributions of population growth, population aging, and epidemiological change to changes in absolute burden. Frontier analysis and autoregressive integrated moving average (ARIMA) models were used to assess potential for improvement and forecast age-standardized burden through 2050. In 2023, IBD burden varied substantially across the 96 tropical countries and territories matched to GBD 2023. A higher tropical climate proportion was negatively correlated with the age-standardized incidence rate (ASIR; rho = - 0.279), age-standardized prevalence rate (ASPR; rho = - 0.318), and age-standardized YLD rate (rho = - 0.313). SDI was positively correlated with ASIR (rho = 0.248) and ASPR (rho = 0.270), but negatively correlated with the age-standardized death rate (ASDR; rho = - 0.310), age-standardized YLL rate (rho = - 0.372), and age-standardized DALY rate (rho = - 0.223). Population growth and aging accounted for most increases in absolute burden. For both sexes combined, population growth explained 58.7% of the increase in prevalent cases, 81.2% of the increase in DALYs, and 97.6% of the increase in YLLs. ARIMA forecasts suggested that ASDR would decline from 0.41 to 0.29 per 100,000 between 2024 and 2050. The age-standardized DALY rate was projected to decline from 15.33 to 13.28 per 100,000, and the age-standardized YLL rate from 10.14 to 8.24 per 100,000. Incidence, prevalence, and YLD rates were projected to remain broadly stable. IBD burden in tropical regions varies across climatic and sociodemographic contexts. Climate-related environmental factors may contribute to geographic differences, but this ecological analysis does not support causal inference.
Gong S, Yu J, Zhong F, Zhong P, Lan Q, Zhong X
Gut-Brain Axis-mediated Neurological Manifestations in Inflammatory Bowel Disease: Mechanisms and Disease Spectrum.Meta-analysis Journal of neurogastroenterology and motility | 2026-09-07
Inflammatory bowel disease (IBD) is a chronic immune-mediated disorder of the gastrointestinal tract that is frequently associated with neuropsychiatric comorbidities, such as anxiety, depression, and other neurological disorders. Accumulating evidence suggests that these neuropsychiatric disorders are secondary conditions caused by impaired gut-brain communication. The gut-brain axis connects the gut and the brain via neural, endocrine, and immune signaling pathways, disruption of which is usually caused by intestinal microbiota imbalance, intestinal barrier damage, neuroinflammation and immune activation, and neuroendocrine pathway abnormalities. These pathways constitute the pathological basis of the disease spectrum of neuropsychiatric comorbidities in IBD patients. This article comprehensively reviews the core mechanisms and disease spectrum of gut-brain axis-mediated neurological and mental complications in IBD, and discusses potential therapeutic strategies and challenges.
Sun B, Wang G, Li X, Liu H, Xv H, Wu Q, Li H, Ye X, Wang X, Tong M
Tissue-resident memory T cells in autoimmune chronicity and relapse: mechanisms and therapeutic implications.Review International immunopharmacology | 2026-09-07
Tissue-resident memory T (Trm) cells are a specialized subset of memory T cells that persist in peripheral tissues (skin, joints, intestine) without recirculating, serving as a frontline defense against pathogen reinfection. This protective function is exemplified by interleukin-15 (IL-15), C-X-C chemokine receptor type 6, and inducible T-cell co-stimulator signaling that are essential for Trm-mediated immunity against viruses and bacteria. However, the same long-lived persistence becomes detrimental in autoimmunity. Activated autoreactive Trm cells accumulate in lesions of psoriasis, rheumatoid arthritis, inflammatory bowel disease, vitiligo, and other conditions. Upon activation by autoantigens or inflammatory cues, they settle in tissues, continuously produce pro-inflammatory cytokines (interferon-gamma, tumor necrosis factor-alpha, IL-17), directly mediate tissue damage, and recruit other immune cells, thereby amplifying chronic inflammation. Their persistence drives disease relapse, lesion chronicity, and tissue-specific confinement. Thus, Trm cells embody a double-edged sword-essential for local immune protection but also important connectors linking autoimmune initiation to chronic pathology maintenance. In this review, we summarized recent advances in Trm cell biology and examined their growing implications in the pathogenesis of autoimmune diseases. We further discuss the molecular and cellular mechanisms through which Trm cells drive organ-specific, chronic inflammatory responses, underscoring their role across diverse autoimmune disorders. Hopefully, the emerging therapeutic strategies aiming at modulating Trm cell generation, persistence, and function will highlight both the promise and obstacles in translating these approaches into clinical practice.
Huang AF, Liu Z, Xu WD
Low-Dose Naltrexone in Crohn’s Disease: A Prematurely Terminated Randomized Trial Showing Reduced Fatigue Without Clinical or Endoscopic Benefit. Digestive diseases and sciences | 2026-09-06
Crohn’s disease (CD) is often refractory to standard therapies, and patients are sometimes reluctant to initiate immunosuppressive therapy, prompting interest in novel treatments such as low-dose naltrexone (LDN). To evaluate the efficacy of LDN for induction of remission in patients with mild-to-moderate active CD. We conducted a multicenter, double-blind, placebo-controlled trial in 7 hospitals in the Netherlands. Adults with active CD (defined by mucosal ulcers on endoscopy and Simple endoscopic score for CD 3-15) were randomized 1:1 to LDN 4.5 mg once daily or placebo for 12 weeks. The primary endpoint was endoscopic remission at week 12. Secondary endpoints included clinical and endoscopic response, safety and patient-reported outcome measures. The trial was stopped early due to futility. Forty-one patients were randomized. After 12 weeks, endoscopic remission occurred in 1 (5.6%) vs. 3 (18.8%) patients for LDN and placebo (p=0.233), respectively. Clinical remission occurred in 22.2% (LDN) vs. 70.0% (placebo) (p=0.037). No serious adverse events were reported. For the FACIT-Fatigue questionnaire, the median difference after 12 weeks was 2.5 (IQR 0-7) for LDN vs. -3 (IQR -7-2) for placebo (p=0.012). Additionally, patient-reported outcomes showed no significant difference between LDN and placebo. LDN was not effective for inducing remission in CD and showed no benefit over placebo. Despite not being an effective treatment for clinical and endoscopic outcomes, it may enhance better quality of life by reducing fatigue symptoms. Future studies are needed to clarify its potential benefit on fatigue in patients with inflammatory bowel disease.
van de Pol N, Paulides E, Wolfhagen FHJ, West RL, Holster IL, Verweij KE, de Vries AC, Fuhler GM, van der Woude CJ
Bromodomain inhibitors in autoimmune diseases.Review Immunotherapy | 2026-09-06
Autoimmune diseases are very common worldwide. The immune system becomes dysregulated in a pro-inflammatory direction. Bromodomains play a crucial role in the regulation of many inflammatory pathways, including mitogen-activated protein kinase, nuclear factor kappa B, and interleukins. Bromodomain inhibitors could allow for better autoimmune disease control and reduction of symptom severity than currently available treatment due to their direct integration into the epigenetic mechanism. This review focuses on drugs currently being tested and how their mechanisms of action are beneficial in treatment of rheumatoid arthritis, osteoarthritis, fibrosis, cirrhosis, lupus, inflammatory bowel disease. The aim of this review is show Bromodomain inhibitors as a new possible treatment strategy for a variety of autoimmune diseases. The study was conducted by selecting articles from the PubMed database published between 2011 and 2026; for some studies describing the basic pathophysiology of the diseases, this period was extended to 2002.
Szczepanik M, Pociej W, Kulpa J, Senko J, Jerzyńska O, Pawlik A
Endocannabinoid system dysregulation in non-communicable diseases: implications for skeletal muscle health.Review Experimental gerontology | 2026-09-04
Non-communicable diseases (NCDs) and their associated skeletal muscle (SkM) degeneration substantially contribute to morbidity and mortality. Interestingly, the endocannabinoid system (ECS) is increasingly recognized as an important regulator of both NCD pathophysiology and SkM plasticity. This narrative review summarizes the interplay between the ECS, NCDs and SkM degeneration - a potentially interesting triad that has not yet been comprehensively described, but may stimulate future research into the role of ECS-targeted interventions in the context of disease-associated SkM wasting. Therefore, we performed a narrative synthesis of (pre)clinical studies, focusing on alterations in ECS components (endocannabinoids, enzymes, receptors), the effects of ECS modulation (e.g. receptor (ant)agonism or enzyme inhibition), and SkM degeneration symptoms, across various (models of) NCDs. Additionally, the current literature on ECS modulation and SkM degeneration in non-disease models was summarized. The main findings show that ECS composition is consistently altered in different NCDs, including obesity, cancer (cachexia), liver disease, kidney disease, cardiovascular disease and inflammatory bowel disease. Pharmacological or genetic ECS modulation has been reported to improve several disease-related outcomes, e.g. insulin resistance, liver fibrosis and renal inflammation, predominantly in preclinical models. These NCDs also exhibit hallmarks of SkM degeneration, including atrophy, impaired regeneration, inflammation, and weakness. Notably, ECS modulation could ameliorate SkM pathology in various preclinical myopathy models, raising the hypothesis of an ECS-disease-muscle axis. However, this hypothesis requires further validation, as studies directly evaluating ECS-based interventions in disease-associated SkM degeneration remain limited. Future research should directly evaluate the existence of this potential ECS-disease-muscle axis by generating more (human) data on ECS modulation in the context of disease-associated muscle wasting.
Vanderbeke K, Dalle S, Koppo K
Bridging the gut and mind: a narrative review of depression in Crohn’s disease and emerging gut-brain axis therapies.Review Frontiers in neuroscience | 2026-08-24
Depression is a highly prevalent and clinically significant comorbidity in Crohn’s disease (CD), a form of inflammatory bowel disease (IBD), and is associated with increased disease activity, hospitalization, and a reduced quality of life (QoL). While traditionally attributed to the psychosocial burden of chronic illness, emerging evidence indicates that depressive symptoms in CD arise from dysregulation of the gut-brain axis (GBA), a bidirectional network linking immune, microbial, and central nervous system (CNS) processes. Chronic intestinal inflammation, characterized by elevated cytokines such as tumor necrosis factor (TNF-α) and interleukin-6 (IL-6), may influence brain function through vagal signaling, hypothalamic-pituitary-adrenal (HPA) axis activation, and neuroimmune pathways. Concurrently, epithelial barrier dysfunction and microbial dysbiosis promote translocation of bacterial products, further amplifying systemic inflammation and neuroimmune signaling. This review consolidates preclinical and clinical evidence linking immune activation, microbial alterations, and neuroimmune signaling to depression in CD. The review compares emerging therapeutic strategies, such as ketamine enantiomers, vagus nerve stimulation, and microbiota-targeting natural compounds, with established therapies like serotonergic antidepressants, cognitive behavioral therapy, and biologic immunotherapies. Across these modalities, therapeutic effects on mood are heterogeneous and often dissociated from improvements in intestinal inflammation, highlighting the multifunctional nature of GBA dysfunction. Overall, these findings suggest that therapeutic responses in CD-associated depression may depend on the extent to which interventions modulate distinct components of the GBA, including immune, neural, and microbial pathways. These observations emphasize the need for integrative treatment strategies that address the multiple contributors of GBA dysbiosis. Future studies incorporating standardized and emerging psychiatric, immunological, and microbiome outcomes will be critical to identifying mechanisms for specific treatment responses in this population.
Pipa Z, Howard N
Pathogenesis & Basic Science (8 papers)
Enhancing intracellular ROS scavenging by chondroitin sulfate-modified ceria nanozymes for the treatment of inflammatory bowel disease and enteropathic arthritis.★ International journal of biological macromolecules | 2026-09-10
Oxidative stress is a key factor in the progression of inflammatory bowel disease (IBD) and enteropathic arthritis, and scavenging excessive intracellular reactive oxygen species (ROS) is an effective therapeutic strategy. Chondroitin sulfate-modified cerium oxide nanozymes (CS-CNPs) were synthesized for the first time in this study with dual-cell targeting properties, which regulated the redox homeostasis of the inflammatory sites of the colon and joints through scavenging intracellular ROS, and thus treating IBD and enteropathic arthritis. The results showed that CS-CNPs possessed multiple mimetic antioxidant enzyme activities and could target inflammatory intestinal epithelial cells and macrophages to scavenge ROS. The good cellular targeting of CS-CNPs enhanced the ability to scavenge ROS from inflammatory cells in the colon of colitis mice, and they produced a good IBD therapeutic effect by inhibiting the intestinal inflammatory response and repairing the damaged intestinal mucosal barrier. In addition, for the treatment of experimental enteropathic arthritis, CS-CNPs demonstrated colonic and joint inflammatory site targeting, and exerted anti-inflammatory effects by scavenging ROS. The conveniently synthesized dual-targeted nanozymes lay the foundation for “kill two birds with one stone” in treating IBD and enteropathic arthritis, as well as an effective solution for the multi-targeted treatment of oxidative stress-related diseases.
Xing Y, Kang F, Chen C, Lan J, You C, Dong K, Zhang Y
Dioscin activates myeloid AMPK to restore Lgr5⁺ stem cell homeostasis and promote mucosal repair in ulcerative colitis. Pharmacological research | 2026-09-10
Ulcerative colitis (UC) is a chronic relapsing inflammatory disease with limited efficacy in achieving durable mucosal healing and preventing dysplasia. Macrophage-intestinal stem cell (ISC) crosstalk plays a central role in epithelial regeneration and tumorigenic transition but remains therapeutically underexplored. Here, we show that Dioscin, a natural steroidal saponin from Dioscoreae Rhizoma, alleviates DSS-induced acute colitis and AOM/DSS-induced chronic colitis-associated dysplasia by reprogramming macrophage-dependent ISC homeostasis. Dioscin significantly reduced disease severity, suppressed inflammatory macrophage infiltration, and restored Lgr5⁺ ISC compartments, whereas macrophage depletion abolished these protective effects. In vitro, Dioscin inhibited M1 polarization of LPS/IFN-γ-stimulated macrophages, improved epithelial barrier integrity, and enhanced ISC proliferation in organoid systems via modulation of macrophage-conditioned signaling. Mechanistically, IL-1β was identified as a key macrophage-derived mediator linking inflammatory activation to ISC dysfunction. Importantly, Dioscin directly interacted with catalytic α1 subunit of AMP-activated protein kinase (AMPKα1), activated AMPK/Raptor signaling, and suppressed mTORC1-dependent inflammatory responses, while pharmacological inhibition with Compound C or myeloid-specific deletion of AMPKα1 (Prkaa1ᶠˡ/ᶠˡ, nLysM-Cre) abrogated its effects. Collectively, Dioscin ameliorates experimental colitis and dysplasia by activating myeloid AMPK signaling, inhibiting IL-1β-driven macrophage-ISC dysregulation, and restoring epithelial regeneration, highlighting macrophage metabolic reprogramming as a therapeutic strategy and identifying myeloid AMPK as a potential target for UC intervention.
Huang N, Lu S, Zhong Q, Mai C, Cong B, Wang L, Huang B, Liu B, Hu Y, Zhang X
Next-Generation Solid Dispersion of Andrographolide Attenuated Inflammation and Oxidative Stress in an Activated RAW264.7 Macrophage-Based In Vitro Model Relevant to Ulcerative Colitis. AAPS PharmSciTech | 2026-09-08
Ulcerative colitis (UC) is fundamentally mediated by macrophage-driven immune dysregulation that amplifies mucosal inflammation. Andrographolide (AGD) has potent anti-inflammatory and antioxidant properties; however, AGD shows poor water solubility and bioavailability. To surmount these challenges, next-generation solid dispersion of AGD with soluplus and TPGS was engineered via the solvent evaporation method. Optimized SD8 demonstrated a ~ 7.14-fold upsurge in solubility, 18.78 ± 0.98% drug content, 93.86 ± 3.19% assay, micellar colloid size of 220.5 ± 20.8 nm, and ζ-potential of -4.18 ± 0.03 mV in aqueous dispersion. ATR-FTIR and 1H-NMR analyses indicated that the -OH group of AGD participated in intermolecular hydrogen bonding with soluplus and TPGS. Moreover, the halo diffraction pattern, the vanishing of the endothermic peak, the lack of birefringence under polarized light, and the loss of crystallinity collectively confirmed the amorphous nature of SD8. SD8 exhibited ~ 2.06-fold decline of contact angle, ~ 4.70- and ~ 2.94-fold boosts in dissolution rate in simulated intestinal fluid (SIF) and simulated colonic fluid (SCF), respectively, and ~ 40.7-fold upsurge in apparent permeability coefficient compared to AGD. SD8 markedly enhanced cytoprotection over AGD, evidenced by significantly lower IC₅₀ values in both lipopolysaccharide (LPS)-activated (7.17 ± 0.15-µg/mL; P < 0.0001) and H2O2-exposed (7.92 ± 0.15-µg/mL; P < 0.01) RAW264.7 macrophages. SD8 significantly suppressed LPS-induced NO production (P < 0.05) and pro-inflammatory mediators (IL-1β, IL-6, TNF-α; P < 0.0001). SD8 markedly reduced ROS levels, significantly restored antioxidant enzymes SOD (P < 0.0001), CAT (P < 0.001), GSH (P < 0.0001), and lowered TBARS (P < 0.0001) with respect to H2O2-exposed RAW264.7 cells. In conclusion, SD8 represents an auspicious drug delivery tactic for further preclinical evaluation to advance its translational potential in the therapeutic management of UC.
Devangan P, Chandanpalli DK, Mourya A, Madan J
Determinants of enteric hyperoxaluria in the SAMP1/YitFc mouse model of spontaneous ileitis.★ Gut microbes | 2026-09-06
Enteric hyperoxaluria (EH) results from increased oxalate bioavailability in the gastrointestinal (GI) tract, often affecting patients with inflammatory bowel disease (IBD). We investigated the pathophysiology of EH in an ileitis mouse model, hypothesizing that fat malabsorption, increased gut permeability, and microbial shifts collectively contribute to the hyperoxaluric phenotype in the setting of GI tract inflammation. SAMP1/YitFc (SAMP1) mice and their parental AKR controls were fed one of three diets varying in fat content (10%, 45%, or 60% kcal), each supplemented with 1% oxalate, for 6 weeks. Plasma (P), urine (U), oxalate (Ox), and creatinine (Cr) levels were measured, while stool lipid species were analyzed using mass spectrometry. Intestinal permeability was assessed using sucralose and 13C2 oxalate gastric gavage in SAMP1 and AKR mice. Histology, qPCR, and Western blotting were performed on kidney, liver, and GI tissues. Microbial DNA was analyzed at the community, genus, and functional levels. Changes in bacterial metabolic pathways were investigated in the mice fed the highest fat content. The oxalobiome of SAMP1 and AKR mice was characterized using our bioinformatics pipeline. On high-fat diets, SAMP1 mice had higher UOx, POx, and PCr levels than AKR mice. Increased levels of diacylglycerols and free fatty acids in SAMP1 stool samples suggested fat malabsorption. A decrease in ZO1 and occludin intestinal expression, coupled with significantly increased urinary sucralose and oxalate levels, indicated increased intestinal permeability. Microbiome analysis revealed the enrichment of Lactobacilli and Bacteroides in SAMP1 mice, with bacterial pathways favoring lipid synthesis and glyoxylate metabolism. Ileal SLC26A6 protein expression was significantly reduced in SAMP1 mice. SAMP1 mice also developed progressive kidney injury with interstitial inflammation. These findings highlight fat malabsorption as a central pathophysiologic disturbance in EH that reduces luminal calcium availability for oxalate binding, is associated with enhanced intestinal permeability, and accompanies microbiome and enzymatic pathway alterations.
Zaidan N, Jaber K, Ho M, Zhou B, Pei Z, Bui ML, Cardozo L, Merritts K, Mishra R, Xiong X
Community: Component based differential cell communication analysis in large multi-sample case-control scRNAseq datasets. iScience | 2026-08-26
Changes in cell-cell communication during disease can result from shifts in tissue composition, variations in the proportion of cells engaged in signaling, and differences in ligand-receptor expression. To address this, we developed community, an R package designed for differential communication analysis in multi-sample case-control scRNAseq datasets. Community reconstructs interactions by evaluating cell type abundance, the active fraction of cells, and their expression levels. This method identifies communication patterns that are upregulated, downregulated, unchanged, or compensated. Applied to ulcerative colitis, melanoma under immune checkpoint inhibitor treatment, and acute myeloid leukemia, community captured disease- and response-associated communication changes, including increased communication in ulcerative colitis, reduced immunosuppressive signaling in melanoma responders, and decreased immune communication in AML. Comparisons with existing tools showed improved robustness to outlier-driven signals and better scalability. These component-level analyses help connect altered communication patterns to biological mechanisms in healthy and disease states.
Solovey M, Celik MA, Salcher FR, Güleç C, Abdalfattah M, Ali MIH, Heinig M, Scialdone A, Ziemann F, Colomé-Tatché M
Celastrol ameliorates ulcerative colitis by inhibiting HSP90-mediated necroptosis of intestinal epithelial cells. Frontiers in pharmacology | 2026-08-21
Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by intestinal barrier dysfunction and epithelial cell death. Necroptosis of intestinal epithelial cells (IECs) mediated by the RIPK1/RIPK3/MLKL pathway has emerged as a key driver of UC progression. Celastrol, a bioactive compound from Celastrus wilfordii, has shown anti-inflammatory potential, but its effect on necroptosis in UC remains unclear. A dextran sulfate sodium (DSS)-induced UC mouse model and a TSZ-induced HT-29 cell necroptosis model were established. Disease activity, colon length, histology, mucus barrier integrity, and tight junction protein expression were evaluated. Western blotting, immunofluorescence, qRT-PCR, and a cellular thermal shift assay (CESTA) were used to assess necroptosis and potential targeting of HSP90. Celastrol significantly improved body weight, disease activity index, and colon length, while restoring mucus secretion and tight junction proteins (ZO-1, Occludin, Muc-2). It reduced phosphorylation of RIPK1, RIPK3, and MLKL both in vivo and in vitro, decreased pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), and attenuated TUNEL-positive IEC death. CESTA indicated that celastrol increased HSP90 thermal stability, suggesting HSP90 engagement. Celastrol ameliorates DSS-induced colitis by inhibiting HSP90-mediated necroptosis of intestinal epithelial cells, supporting its potential as a candidate for UC therapy.
Lu K, Wang Y, Shi Y, Liu S, Shao Y, Wang Z, Xu E
Astragaloside IV ameliorates DSS-induced intestinal epithelial barrier dysfunction associated with modulation of tight junction proteins and MLCK/p-MLC and MyD88/TRAF6 signaling pathways. Frontiers in pharmacology | 2026-08-21
The integrity of the intestinal mucosal barrier is critical in the pathogenesis of Inflammatory Bowel Disease (IBD). While Astragaloside IV (ASIV) possesses potent anti-inflammatory properties, its specific effects on intestinal epithelial barrier function and the underlying mechanisms involving the Myosin Light Chain Kinase (MLCK) and Myeloid Differentiation Primary Response 88/TNF Receptor-Associated Factor 6 (MyD88/TRAF6) pathways in colitis remain elusive. This study aimed to investigate the protective effects of ASIV on tight junction (TJ) proteins and inflammatory signaling in dextran sulfate sodium (DSS)-induced colitis. A chronic colitis model was established in wild-type C57BL/6 mice using four cycles of DSS administration. ASIV (30 mg/kg/day) was administered orally starting from day 14. Disease activity index (DAI), colon length, and histopathological changes were assessed. Intestinal barrier function was evaluated by measuring bacterial translocation, colonic permeability to fluorescein isothiocyanate (FITC)-dextran, and serum lipopolysaccharide (LPS) levels. The expression of TJ proteins (ZO-1, Occludin, JAM-A, Claudin-2) and signaling molecules (MLCK, phosphorylated myosin light chain (p-MLC), MyD88, TRAF6) was determined by Western blot and quantitative real-time PCR (qRT-PCR). Representative immunofluorescence localization of Claudin-2 and ZO-1 in colonic tissues was included as supplementary qualitative evidence of tight junction remodeling. ASIV treatment significantly attenuated DSS-induced weight loss, colon shortening, and histopathological damage (p < 0.05). Furthermore, ASIV markedly reduced colonic permeability, serum LPS levels, and bacterial translocation to mesenteric lymph nodes (p < 0.01). At the molecular level, ASIV reversed the DSS-induced downregulation of sealing TJs (ZO-1, Occludin, JAM-A) and suppressed the upregulation of the pore-forming protein Claudin-2 (p < 0.05). These protective effects were accompanied by significant inhibition of TNF-α mRNA expression, reduced MLCK protein expression, decreased MLC phosphorylation, and suppression of MyD88/TRAF6 signaling. ASIV effectively restores intestinal epithelial barrier integrity in experimental colitis. These protective effects are associated with rebalancing of TJ protein expression and localization and may be partially linked to attenuation of the TNF-α/MLCK/p-MLC and LPS/MyD88/TRAF6 signaling axes. These findings support ASIV as a promising barrier-protective candidate for mucosal homeostasis in IBD, while future cellular and pathway-intervention studies are needed to establish direct causality.
Yang M, Wang Y, Jia W, Duan Z, Wang J, Huo X, Xu S, Duan Y, Zhang X
Mechanism of Shao Kuiling Decoction in Treating Ulcerative Colitis: A Network Pharmacology and Molecular Docking Study. Current computer-aided drug design | 2026-08-21
Shao Kuiling Decoction (SKD) is used in the long-term management of Ulcerative Colitis (UC), but its molecular basis remains unclear. Because SKD is a multicomponent formula, a computational approach is useful for identifying candidate compounds, targets, and pathways for further validation. Active compounds in SKD were screened from TCMSP using oral bioavailability and drug-likeness criteria. Putative targets were predicted and intersected with UC-related targets. Shared targets were analyzed by protein-protein interaction network construction, GO/KEGG enrichment, molecular docking, and 100 ns molecular dynamics simulations. A total of 145 active compounds and 94 shared SKD-UC targets were identified. AKT1, TNF, and TP53 were the main hub targets, and the PI3K-Akt and MAPK pathways were the most enriched. Molecular docking showed favorable binding of the major compounds to core targets, with kaempferol‑TNF showing the strongest binding energy of -8.9 kcal/mol and β‑sitosterol‑AKT1 showing -8.4 kcal/mol. Molecular dynamics simulations revealed that the kaempferol‑TNF and β‑sitosterol‑AKT1 complexes remained stable over 100 ns, with RMSD values plateauing at 0.20-0.25 nm and 0.15-0.20 nm, respectively, and maintained consistent hydrogen bonding. In contrast, the acacetin‑TP53 complex showed greater fluctuations, indicating weaker stability. These findings suggest that SKD may exert therapeutic effects in UC through coordinated modulation of multiple targets and pathways involved in inflammation and epithelial repair. In a broader context, this study provides a systems-level basis for understanding the potential mechanism of SKD in UC and offers focused directions for future experimental validation. SKD may exert anti-UC effects through a multi-component, multi-target mechanism involving AKT1/TNF/TP53-associated networks and PI3K-Akt/MAPK signaling.
Wu X, He Z, Ren W, Zhao B, Tseng Y
DOI: 10.2174/0115734099474992260810095531 | View on PubMed →
AI & Machine Learning (6 papers)
Pan-cancer screening and integrative multi-omics and deep learning reveal the prognostic significance of an IBD-CRC shared host-microbe signature in bladder urothelial carcinoma. Translational oncology | 2026-09-09
The prognostic relevance of inflammatory bowel disease (IBD)-colorectal cancer (CRC) shared host-microbe signatures in non-intestinal epithelial malignancies remains unclear. This study aimed to evaluate the prognostic and biological significance of an IBD-CRC shared host-microbe interactome signature in bladder urothelial carcinoma (BLCA). Gene set variation analysis (GSVA) was used to assess the activity of the IBD-CRC shared signature across The Cancer Genome Atlas (TCGA) pan-cancer solid tumor cohorts, including lung, liver, colorectal, and urinary system tumors. In BLCA, weighted gene co-expression network analysis (WGCNA) and least absolute shrinkage and selection operator (LASSO)-Cox regression were applied to construct a prognostic risk model, which was validated in independent transcriptomic cohorts. An attention-based multiple instance learning (MIL) model was developed to predict the LASSO-derived high- or low-risk group from H&E whole-slide images (WSIs), using TCGA cases for training and internal validation and an independent institutional cohort of 39 BLCA patients for external validation. Molecular subtype, immune infiltration, immunohistochemistry (IHC), machine learning, single nucleotide variation/copy number variation (SNV/CNV), single-cell/spatial transcriptomics, and WSI-based deep learning analyses were integrated to characterize the biological relevance of the signature. High GSVA scores were significantly associated with poor prognosis in BLCA. The LASSO-derived high-risk group was enriched in basal/squamous molecular features and exhibited an immune-infiltrated but immunosuppressive tumor microenvironment, characterized by increased immunosuppressive cell infiltration and elevated immune checkpoint expression. Conventional IHC markers supported distinct subtype-related protein phenotypes between risk groups. Single-cell and spatial transcriptomic analyses revealed that malignant cells with high signature activity were enriched in Wnt, Hippo, and cell adhesion pathways. The WSI-based MIL model achieved an area under the curve (AUC) of 0.852 in the internal validation cohort. Machine learning and SNV/CNV analyses further characterized key molecular features associated with the LASSO risk score, including AKR1B1, LY6E, MEST, and others. Pan-cancer characterization of AKR1B1 across multiple malignancies, including lung adenocarcinoma (LUAD), liver hepatocellular carcinoma (LIHC), and kidney renal clear cell carcinoma (KIRC), revealed cancer-type-specific associations with immunosuppressive microenvironmental features and tumor stemness. The IBD-CRC shared host-microbe signature has significant prognostic value in BLCA and is associated with basal/squamous differentiation, immunosuppressive microenvironmental features, genomic alteration patterns, and malignant cell functional heterogeneity. The integrated multi-omics framework and externally validated pathology AI model provide potential tools for BLCA risk stratification and biological interpretation.
Zhan C, Xu T, Lai H, He Y, Chen F, Liu R, Wang B, Wang Z, Liang H, Zeng D
The tire antioxidant derivative 6PPD-quinone exacerbates IBD by targeting NR1H4-mediated lipid metabolism and mitochondrial dysfunction in human colon epithelial cells. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association | 2026-09-04
N- (1,3-Dimethylbutyl)-N’-phenyl-p-phenylenediamine quinone (6PPD-Q), a tire rubber antioxidant derivative, accumulates in air, soil, and water and has been found in urine, blood, and cerebrospinal fluid, posing significant health risks. Although 6PPD-Q exhibits intestinal toxicity, its role in inflammatory bowel disease (IBD) remains unclear. The objective of this study was to identify key molecular targets of 6PPD-Q in IBD and to validate their involvement in 6PPD-Q-induced intestinal epithelial cell injury. Using network toxicology, machine learning, molecular docking, and in vitro experiments in human intestinal epithelial cells, we identified 60 overlapping 6PPD-Q-IBD targets, enriched in lipid metabolism, oxidative stress, and inflammation. Multi-model machine learning screened six core genes (NR1H4, ANXA5, SPARC, PCK1, PDK2, and CFB), with NR1H4 as a key mediator. Molecular docking showed strong binding of 6PPD-Q to NR1H4, exceeding that of its parent compound. In vitro experiments confirmed that 6PPD-Q caused lipid droplet and cholesterol accumulation, mitochondrial dysfunction (manifested as ATP synthesis inhibition, mitochondrial ROS burst, decreased membrane potential, and mitochondrial fragmentation), and significantly upregulated the levels of pro-inflammatory cytokines IL-6, TNF-α, and IL-8, thereby triggering inflammatory responses. Moreover, 6PPD-Q exposure significantly downregulated NR1H4 expression. These findings reveal that 6PPD-Q increases IBD risk by interfering with lipid metabolism, disrupting mitochondrial function, upregulating inflammatory cytokines, and downregulating NR1H4, providing important evidence for understanding the risk posed by this emerging environmental pollutant to IBD and for developing preventive strategies.
Wu P, Hu W, Chen G, Zhao X, Zhang X
Integrative Machine Learning and Single-Cell RNA Sequencing Reveals Timp1+ Stromal Cells as Key Drivers in Ulcerative Colitis. Journal of inflammation research | 2026-09-03
Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease (IBD). The role of stromal cells in UC pathogenesis is increasingly being recognized, yet their functional subsets and underlying molecular mechanisms remain poorly defined. To integrate multiple transcriptomic datasets, combined weighted gene co-expression network analysis (WGCNA) with machine learning algorithms for the identification of robust core biomarkers of UC and to resolve the cell-subset-specific expression and pathogenic mechanisms of candidate genes using single-cell RNA sequencing (scRNA-seq). Three GEO datasets (GSE38713, GSE3365, and GSE24287) were merged after batch correction. WGCNA, together with five machine learning algorithms, LASSO, random forest, Boruta, gradient boosting machine, and XGBoost, were applied to screen for core genes. External validation was performed using two independent datasets, GSE92415 and GSE179285, and a DSS- of DSS-induced chronic colitis. The cell- subset-specific expression and mechanisms of candidate genes were dissected by scRNA- sequencing. Three core genes, TIMP1, S100A12, and ALPL, were identified. External validation showed that TIMP1 and S100A12 were consistently upregulated in both independent datasets, whereas ALPL was significantly upregulated in GSE92415, but not in GSE179285. TIMP1 was selected for further investigation based on its differential significance. In the DSS-induced chronic colitis mouse model, the area of Timp1-positive colon tissue increased by 2.3-fold compared to in the controls. scRNA-seq revealed that Timp1 was specifically enriched in a stromal cell subset of the mouse colon. Pseudotime trajectory analysis indicated that Timp1⁺ stromal cells predominantly localized to late differentiation stages, with their expression dynamics undergoing a sequential transition from matrix remodeling and angiogenesis to immune regulation. Cell-cell communication analysis further identified the enrichment of the Ppia-Bsg signaling axis between Timp1⁺ stromal cells and epithelial cells. Timp1 was specifically enriched in a colonic stromal cell subset in UC mice, and this subset exhibited a shifted differentiation trajectory and enhanced communication with epithelial cells. These findings provide candidate targets for the molecular diagnosis of UC and highlight the translational potential of targeting Timp1⁺ stromal cells or their downstream signaling pathways for stromal-directed therapeutic intervention.
Xu X, Du L, Li Z, Jia X, Du Y, Yang Q, Cai Y
Emerging antimicrobial peptides in gastrointestinal disorders: Dual role in immunity and therapy.Review World journal of gastrointestinal pharmacology and therapeutics | 2026-09
Antimicrobial peptides (AMPs) are small, cationic effectors of innate immunity that are central to gastrointestinal homeostasis and increasingly attractive as therapeutics for infection, inflammation, and malignancy. Produced by intestinal epithelial and immune cells, AMPs such as defensins and cathelicidins act as frontline regulators, responding to microbial cues through pattern-recognition receptors, shaping microbiota composition, reinforcing the mucosal barrier, and tuning the balance between pro-inflammatory and anti-inflammatory signalling. This review frames AMP biology around a central duality: The same peptides that defend the gut can, when dysregulated in concentration, location, or context, contribute to pathology, from the α-defensin deficiency that initiates ileal Crohn’s disease to the concentration-dependent switch by which LL-37 turns from a wound-healing mediator into a tumour-promoting one. This duality dictates therapeutic strategy, favouring restoration where disease arises from deficiency and restraint where it arises from aberrant signalling. We examine the mechanistic basis of AMP action (membrane disruption, intracellular targeting, and receptor-mediated immunomodulation) and evaluate preclinical and clinical evidence across inflammatory bowel disease, enteric infection, and gastrointestinal cancers, drawing the recurring lesson that microbiological success rarely guarantees clinical benefit. Persistent barriers of proteolytic instability, narrow therapeutic windows, and manufacturing cost are increasingly addressed through convergent advances in artificial intelligence-guided peptide design, sequence stabilisation, gut-targeted and stimulus-responsive delivery, and engineered live biotherapeutics that produce peptides in situ. Together, these developments are transforming AMPs from endogenous immune mediators into next-generation precision therapeutics for gut disease-agents designed to be not merely potent, but deliverable, selective, and stable where needed most.
Selvaraj K, Girish C
Machine learning-driven identification and experimental validation of key biomarkers in the bile acid metabolic pathway associated with ulcerative colitis. Frontiers in immunology | 2026-08-24
Bile acids are shown to participate in inflammatory responses. This study was designed to investigate the functions of bile acid metabolism-associated genes (BAMGs) in ulcerative colitis (UC), identify the potential biomarkers based on eleven machine learning algorithms. Seven independent UC transcriptomic datasets were retrieved from the GEO database. Differentially expressed genes, weighted gene co-expression network analysis (WGCNA), and multiple machine learning algorithms were integrated to identify key BAMGs. Subsequently, enrichment analysis, immune cell analysis and single cell analysis were performed to explore the biological functions and immunological characteristics. The dextran sulfate sodium (DSS) induced colitis model in mice was then established and validated the results through western blot and immunohistochemical (IHC) analysis. In addition, peripheral blood samples were collected from UC patients for the detection of feature gene expression by quantitative real-time PCR (RT-qPCR). Through integrative analysis, three feature BAMGs (CH25H, SLC23A1 and PHYH) were identified. Unsupervised clustering based on the three-gene signature stratified UC patients into two distinct subgroups exhibiting divergent immune status. In DSS-treated mice, western blot and IHC confirmed significantly reduced SLC23A1 and PHYH protein levels and elevated CH25H protein expression in colonic tissues. RT-qPCR analysis of PBMCs from UC patients showed consistent gene expression. Immune cell analysis showed obvious association between the key BAMGs and inflammatory cells including naïve B cells, neutrophils, monocytes, CD8 T cells, and macrophages. Single-cell analysis revealed that the three feature genes were differentially expressed across T- and B-cell subsets, indicating their potential involvement in UC. This study identified a novel of BAMGs and preliminary revealed their interaction with immune cells in the development of UC. Downregulation of SLC23A1 and PHYH and upregulation of CH25H may contribute to UC pathogenesis and represent potential biomarkers.
Wu Y, Gu D, Liu J, Yang Y, Wang Y, Wang Y, Mu Y, Sun R, Huang B
Gut microbiota-derived metabolites target C5AR1/KDM2A/HCAR3 axis in inflammatory bowel disease: a multi-machine learning algorithms and molecular docking study. Frontiers in cellular and infection microbiology | 2026-08-21
Inflammatory bowel disease (IBD) is a chronic recurrent disorder. Gut microbiota-derived metabolites regulate intestinal homeostasis, but their molecular mechanisms in IBD remain unclear. Current studies lack systematic “microbiota-metabolite-target” network mining with multi-method validation. This study integrates network pharmacology, three machine learning algorithms, and molecular docking to construct this regulatory network in IBD. Transcriptome data were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified using limma (p < 0.05, |log2FC| > 0.5). Weighted gene co-expression network analysis (WGCNA) with an optimal soft threshold of β = 7 was performed to identify key module genes. Candidate genes were obtained by intersecting DEGs, gut microbiota-associated genes from the gutMGene database, and WGCNA module genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to explore the functional roles of candidate genes. Core genes were identified using three machine learning algorithms (LASSO, Boruta, and SVM-RFE), followed by protein-protein interaction (PPI) network analysis. Molecular docking was performed to assess the binding affinities between hub proteins and gut microbiota-derived metabolites. A total of 885 DEGs were identified between the IBD and control groups, including 463 upregulated and 422 downregulated genes. WGCNA identified 280 key module genes from the purple and yellow modules. The intersection of DEGs, gut microbiota-associated genes, and WGCNA module genes yielded 19 core candidate genes. PPI network analysis combined with three machine learning algorithms jointly identified C5AR1, KDM2A, and HCAR3 as core hub genes. ROC curve analysis demonstrated that all three hub genes achieved AUC values greater than 0.7 in both the training and validation sets, indicating excellent diagnostic performance for IBD. Enrichment analysis revealed significant associations with the TNF, NF-κB, and IL-17 signaling pathways. Molecular docking confirmed stable binding of C5AR1 with 1,3-Diphenylpropan-2-Ol (-7.87 ± 0.83 kcal·mol-¹) and HCAR3 with 3-Indolepropionic Acid (-6.35 ± 0.70 kcal·mol-¹), both below -5.0 kcal·mol-¹. This study first constructs a “gut microbiota-metabolite-hub gene” axis in IBD, providing a computational framework for microbiota-targeted precision therapy, and identifying C5AR1/KDM2A/HCAR3 as computationally predicted diagnostic biomarkers and 1,3-Diphenylpropan-2-Ol/3-Indolepropionic Acid as candidate intervention molecules that warrant further experimental validation.
Hu S, Fu L, Gao J, Guo Q, Han S
Pediatric IBD (5 papers)
Surgical Outcomes for Pediatric Patients with Neurodevelopmental Disorders and Inflammatory Bowel Disease. Journal of pediatric surgery | 2026-09-10
Neurodevelopmental disorders (NDD) are associated with inflammatory bowel disease (IBD). For children with NDD, difficulties with assessment and communication can complicate care. We sought to define the perioperative outcomes for children with NDD and IBD who undergo colectomy. Using the National Surgical Quality Improvement Pediatric (NSQIP-P) database from 2019 to 2023 we identified children with IBD who underwent total or partial colectomy. NDD diagnosis was identified using the NSQIP-P variable for “developmental delay”. Outcomes were analyzed using Fisher’s exact test for categorical outcomes and Rank Sum test for contiguous variables, followed by multivariable logistic regression. Of 1,978 pediatric patients who underwent a colectomy, 71 (3.6%) were identified as having NDD. NDD patients had longer average hospital lengths of stays (LOS) prior to their operation (9.66 vs. 3.71 days, p=0.0045) but had no difference in LOS post-operatively. They required more nutritional support pre-operatively (aOR 2.30, 95% 1.38-3.83, p=0.001) but were not more likely to be discharged on total parenteral nutrition (aOR 2.2, 95% CI 0.9-5.0, p=0.07). Patients with NDD were more than eight times as likely to be diagnosed with pneumonia postoperatively (aOR 8.84, 95% CI 2.15-36.29, p=0.003). Other findings that were significant on univariate analysis did not persist after multivariable analysis. NDD patients have different hospital courses compared to their non-NDD counterparts when undergoing colectomies for IBD. However, this study is limited by the broad NSQIP definition of NDD. Further research would benefit from granularity of NDD diagnoses and perioperative variables in national databases.
Cheng TY, Lee SY, Sehres G, Anderson JE, Kohler JE
Clostridioides difficile in Paediatric Inflammatory Bowel Disease: A Retrospective Cross-Sectional Analysis of the East London Region. Journal of paediatrics and child health | 2026-09-08
Clostridioides difficile is a major cause of healthcare-associated diarrhoea, and patients with inflammatory bowel disease (IBD) are thought to be highly susceptible to both colonisation and C. difficile-associated disease (CDAD). to characterise rates of C. difficile test positivity among paediatric stool samples submitted for clinical testing at a single East London centre, comparing samples from patients with IBD to those from patients without IBD. Retrospective analysis of stool testing episodes from patients aged ≥ 1 year between April 2020 and November 2022. Samples were tested using glutamate dehydrogenase (GDH) immunoassay, toxin A/B immunoassay, and toxigenic gene polymerase chain reaction (PCR). Fisher’s exact testing compared positivity rates between samples from patients with IBD and those from patients without IBD. In total, 470 stool testing episodes from 334 unique patients were included; 155 samples were from patients with IBD and 315 were from patients without IBD. Overall, 15.9% (n = 75) of testing episodes were positive for GDH and 2.5% (n = 12) for toxin. GDH positivity was significantly lower in the IBD group (7.7%) compared with the non-IBD group (20%) (p = 0.0005). However, there was no statistically significant difference in toxin positivity between IBD (1.3%) and non-IBD (3.2%) groups (p = 0.35), or in the presence of the toxigenic gene (p = 0.16). In this single-centre, laboratory-based cohort of paediatric samples submitted for clinical testing, GDH positivity was lower in samples from patients with IBD than in those from patients without IBD, while toxin positivity did not differ significantly between groups. These findings should not be interpreted as population prevalence estimates, but they support continued vigilance for CDAD in paediatric patients with IBD undergoing clinical testing.
Machta JS, Alexander E, Naik S
Transition of children with chronic gastrointestinal and liver disease to adult care: A multicentre Asian survey of paediatric gastroenterologists. Journal of pediatric gastroenterology and nutrition | 2026-09-07
The rising incidence of chronic gastrointestinal conditions and better survival of children with life-limiting diseases have resulted in the need for continuity of care into adulthood. This study aimed to detail transition practices in paediatric gastroenterology and hepatology within Asia. Paediatric gastroenterologists were invited to complete a web-based survey administered through a regional paediatric gastroenterology society to its members. The questionnaire was designed based on the ‘Transition Policy Survey’ and ‘Barriers to Transition Care in Inflammatory Bowel Disease (IBD) Questionnaire’. One hundred and nine paediatric gastroenterologists from 10 countries participated. Key factors influencing timing of transfer included patients demonstrating responsibility for their own care (mean 3.5 ± standard deviation [SD] 0.6, scale of 1-4, 1 = not important, 4 = very important), knowledge of disease and its prognosis (mean 3.40 ± SD 0.7), and emergence of adult-specific health issues (mean 3.38 ± SD 0.8). The ‘ideal’ age for transition was felt to be 18 (59%). Most clinicians would begin pre-transition preparation 2 years prior. Whilst all felt transition services were important, only 59% provided such care. Services were unavailable (28%) or ad-hoc (11%) in many centres. The top barriers to successful transition were patient-related (36%), parent-related (27%) and lack of engagement with adult subspecialty counterparts (21%). This study provides real-world data regarding transition practices in Asia. Beyond patient-related barriers, parent-related factors (possibly cultural influence) were significant. Transition care programs in the region and those including patients from Asia would need to be cognisant of these issues when planning transition of these patients to adult services.
Ee SC, Vimalesvaran S, Lee WS, Treepongkaruna S, Ukarapol N, Gatcheco F, Ishige T, Koh H, Rajindrajith S, Thapar N
Exclusive enteral nutrition versus the Crohn’s disease exclusion diet for remission induction in pediatric Crohn’s disease: 52-week study. Journal of pediatric gastroenterology and nutrition | 2026-09-03
Nutritional therapy is a cornerstone for the induction of remission in pediatric Crohn’s disease (CD); however, the optimal dietary strategy remains uncertain. This study aimed to compare the short- and long-term therapeutic outcomes of exclusive enteral nutrition (EEN) and the Crohn’s disease exclusion diet (CDED) in a large cohort of children with CD. This historical cohort study included children diagnosed with CD between 2014 and 2023 who were treated exclusively with either EEN or the CDED for the induction of disease remission. Demographic, clinical, and laboratory data were collected over a 52-week follow-up period. A total of 159 patients were included: 75 treated with EEN and 84 with the CDED. Baseline demographic and disease characteristics were comparable between groups. At 6 weeks, clinical remission was achieved in 58 (77%) children in the EEN group and 63 (75%) children in the CDED group (p = 0.730). Treatment adherence rates were similarly high (EEN 89% vs. CDED 88%, p = 0.810). Week 6 normalization of C-reactive protein (EEN 43% vs. CDED 46%, p = 0.709) and fecal calprotectin <150 mcg/g (EEN 35% vs. CDED 34%, p = 0.982) were also comparable between the groups. A Mucosal Inflammation Noninvasive index score <8 was documented in 52% versus 69% of the groups, respectively (p = 0.219). There were no group differences in rates of disease exacerbation, corticosteroid or biologic therapy use, hospitalizations, or need for surgery during 52 weeks of follow-up. EEN and the CDED demonstrated no significant differences in efficacy across all assessed clinical and biochemical outcomes throughout the 52-week follow-up period.
Pevzner D, Anafy A, Moran-Lev H, Galai T, Amir A, Cohen S, Ziv-Baran T, Yersushalmy-Feler A
Colombian registry of inflammatory bowel disease in pediatrics. Crohn’s & colitis 360 | 2026-08-31
Inflammatory bowel disease (IBD) has significantly increased over the past two decades. However, registries in Latin America remain scarce, prompting the creation of the Colombian pediatric IBD registry for patients under 18 years of age, designed as a continuous and periodically assessed database. A descriptive, longitudinal, ambispective, and multicenter observational study was conducted in children aged 0-18 years between January 1999 and December 2021. The analysis was performed based on the age of onset (Paris classification), with subdivisions for very early onset and phenotypes using the Pediatric IBD-classes algorithm. Data were collected in REDCap and analyzed with STATA 15.1. A total of 209 patients were included, 54.5% male. The median age at diagnosis was 12.3 years (IQR 8.5-14.6). Phenotype distribution included: 104 (53.06%) typical ulcerative colitis (TUC), 52 (26.53%) Crohn’s disease (CD), 18 (9.18%) unclassifiable IBD (U-IBD), 11 (5.61%) colonic Crohn’s disease (CCD), and 11 (5.61%) atypical ulcerative colitis (AUC). The median time to diagnosis was 6.6 months, and treatment began after a median of 11.2 days. Coffee-cultivation zone 39%. Extraintestinal manifestations were reported in 43.9% of cases. Initial treatments included mesalamine ± steroids (35.86%), immunomodulators ± steroids (32%), exclusive/partial enteral nutrition (11.41%), and biologics ± immunomodulators (20.65%), which increased to 57.7% during follow-up. Relapse occurred in 53.26% of patients, while 35.32% achieved remission. This registry highlights the increasing incidence of pediatric IBD in Latin America, providing valuable insights into clinical presentations, diagnostic delays, treatment strategies, and outcomes, while revealing regional and global disparities.
Sarmiento Quintero F, Castañeda Figueroa AM, Mora Quintero DV, Sánchez Franco CP, Jaramillo Barberi LE, Prado Baquero SA, Suárez Urueña MA, Pedraza Peña AN, Peña Hernández S, Martínez Portilla KA
Drug Safety & Pharmacovigilance (3 papers)
Efficacy and tolerability of janus kinase inhibition strategies for moderate-to-severe Crohn’s disease: A systematic review and bayesian network meta-analysis. Therapeutic advances in gastroenterology | 2026-09-09
Crohn’s disease is a chronic inflammatory bowel disease with an expanding therapeutic landscape for moderate-to-severe disease. Janus kinase (JAK) inhibitors have emerged as effective oral treatment options by modulating intracellular inflammatory signalling pathways. This systematic review and Bayesian Network meta-analysis aimed to synthesize randomized trial evidence evaluating JAK inhibition strategies in moderate-to-severe Crohn’s disease. Given the lack of head-to-head trials, indirect comparisons were considered exploratory. Systematic review and Bayesian network meta-analysis of randomized controlled trials (RCTs). Cochrane Central Register of Controlled Trials, MEDLINE (PubMed), Embase, Scopus, and ClinicalTrials.gov were systematically searched from inception to April 2025. A Bayesian NMA was conducted in R. Hazard ratios (HRs) with 95% credible intervals (CrIs) were estimated. Surface under the cumulative ranking curve (SUCRA) values were calculated to rank interventions across efficacy and safety outcomes. The protocol is registered with PROSPERO. Twelve RCTs comprising 25 treatment arms and 5129 patients were included. The network evaluated upadacitinib across six dosing regimens and filgotinib across two. Upadacitinib 45 mg once daily (OD) showed significant efficacy in achieving clinical remission compared to placebo (HR: 2.47; 95% CrI: 1.51-4.10). For endoscopic remission, upadacitinib 24 mg OD ranked highest, followed by upadacitinib 24 mg BID. For endoscopic response, upadacitinib 24 mg OD ranked highest. No statistically significant differences were observed for clinical response. These estimates were associated with very wide credible intervals indicating statistical imprecision. For safety outcomes, no statistically significant differences were observed among various regimens. For Inflammatory Bowel Disease Questionnaire (IBDQ) ≥ 16, all upadacitinib dosing regimens showed a clinically meaningful response. In this NMA, upadacitinib-containing regimens showed the most consistent efficacy signal among evaluated JAK inhibition strategies. However, the evidence network was sparse, limiting the clinical applicability. Treatment rankings should therefore be interpreted as exploratory.
Wazir HU, Mehta K, Shabbir MS, Islam MR, Maaz M, Muzaffar M, Ehsan N, Aliha S, Chauhan A, Khurram A
Influence of Ageing on the Pharmacology, Efficacy and Safety of Oral Targeted Therapies for Inflammatory Bowel Disease: Focus on Janus Kinase (JAK) Inhibitors and Sphingosine-1-Phosphate (S1P) Receptor Modulators.Review Drugs & aging | 2026-09-07
Older adults represent a rapidly expanding subgroup of patients with inflammatory bowel disease, yet they remain markedly under-represented in pivotal clinical trials, limiting age-specific estimates of drug benefit and harm. This review synthesises the available evidence on the influence of ageing on the pharmacology, efficacy and safety of orally administered targeted inflammatory bowel disease therapies, focusing on registered Janus kinase inhibitors (tofacitinib, upadacitinib, filgotinib) and sphingosine-1-phosphate receptor modulators (ozanimod, etrasimod). Because the available age-stratified evidence is sparse and heterogeneous, a narrative review methodology was chosen to map the literature and identify knowledge gaps. We pragmatically report age-related findings using the age cut-offs applied in original studies and map outcomes including clinical and endoscopic response/remission, corticosteroid sparing and adverse drug events of special interest (serious/opportunistic infections, cardiovascular and thromboembolic events, malignancies and treatment discontinuation). Across the limited age-stratified datasets, efficacy appears largely maintained in older patients, but the evidence base is heterogeneous and frequently lacks dedicated analyses. Ageing-related physiological changes, comorbidity, frailty and polypharmacy are expected to modulate pharmacokinetic and pharmacodynamic variability and to amplify the clinical relevance of class-specific safety concerns, particularly infections, major adverse cardiovascular events and malignancy signals with Janus kinase inhibition and initiation-related cardiovascular/conduction considerations with sphingosine-1-phosphate modulation. There is, however, no clear consensus on how ageing-related vulnerability, including frailty and comorbidity burden, should be defined, measured, and reported across studies, which complicates the interpretation and comparison of outcomes. In the absence of robust outcome data for older adults with inflammatory bowel disease, treatment selection should be guided by biological vulnerability (frailty, organ function, comorbidity burden) and structured risk-mitigation strategies, while future research should prioritise age- and frailty-enriched prospective studies with geriatric-relevant outcomes and long-term pharmacovigilance.
Derijks LJJ, Karapinar-Çarkit F, Mujagić Z, van Marum RJ, Pierik MJ
Extracorporeal photopheresis: A comprehensive review from a transfusion medicine perspective.Review Hematology, transfusion and cell therapy | 2026-09-04
Extracorporeal photopheresis is a unique immunomodulatory therapy that involves the ex vivo treatment of leukocytes with 8-methoxypsoralen and ultraviolet A light, followed by reinfusion into the patient. Initially developed for cutaneous T-cell lymphoma, extracorporeal photopheresis has gained recognition for its efficacy in treating various immune-mediated conditions such as graft-versus-host disease, systemic sclerosis, solid organ transplant rejection, and inflammatory bowel diseases. This review outlines the historical evolution, pharmacology of psoralens, mechanisms of action, clinical applications, equipment types, quality control methods and practical aspects for initiating extracorporeal photopheresis. The therapy’s core mechanism, inducing apoptosis and modulating dendritic cell function, promotes immune tolerance and regulatory T-cell expansion. Different inline and offline systems are employed, each with distinct operational and safety considerations. Current evidence supports extracorporeal photopheresis in steroid-refractory graft-versus-host disease and cutaneous T-cell lymphoma, although its role in visceral and long-term disease remains underexplored. Quality control methods such as proliferation assays, flow cytometry, and surrogate markers are discussed in detail. Despite its promise, further randomized trials are necessary to clarify standardized protocols and long-term outcomes.
Rajendran S, Unni H, Murugesan M, Kurup AR, Nayanar SK
Extraintestinal Manifestations (3 papers)
Gut microbiota-derived imidazole propionate promotes primary sclerosing cholangitis via p38 signalling. Nature metabolism | 2026-09-04
Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease of the bile ducts that can lead to biliary cancer and end-stage liver disease. PSC is associated with inflammatory bowel disease and an altered gut microbiota. However, the molecular mechanisms underlying gut-liver interactions in PSC remain poorly characterized. Here we show that the gut microbiota-derived metabolite imidazole propionate (ImP) is a disease driver in PSC. Individuals with PSC have higher circulating ImP levels than individuals with related conditions, and high ImP levels predict reduced survival in PSC. Cholangiocytes exposed to ImP show activated mammalian target of rapamycin complex 1 (mTORC1) signalling and secrete pro-inflammatory and pro-fibrogenic factors. Chronic administration of ImP to mice induces liver inflammation and fibrosis through a p38-dependent mechanism, upstream of mTORC1. We propose that chronic exposure to ImP induces cholangiocyte injury, which alone or in concert with other factors causes clinical worsening of PSC. Therefore, targeting ImP production or signalling may represent therapeutic avenues in PSC.
Molinaro A, Braadland PR, Carpino G, Carreras A, Nikolaidis M, Hanzely P, Beck KR, Ali AH, Bossen L, Frank A
Systemic Corticosteroids in the Perioperative Setting for Prevention of Pyoderma Gangrenosum During Reconstructive Surgery.Case report Journal of drugs in dermatology : JDD | 2026-09
Pyoderma gangrenosum (PG) is classified as a neutrophilic dermatosis, often presenting as a rapidly enlarging ulcer and associated with inflammatory bowel disease, specifically ulcerative colitis and Crohn’s disease. PG has been typically reported to occur after trauma and surgical procedures. We present a unique case of PG following multiple breast augmentation procedures and illustrate various therapeutic strategies to prevent recurrence during subsequent breast reconstruction. The combination of cyclosporine and prednisone was successfully used to prevent PG in this patient when given before and after her third breast surgery.  .
Li LS, Lau WC, Lebwohl M
Biologic and targeted synthetic therapies in ankylosing spondylitis: a pharmacological review.Review Frontiers in pharmacology | 2026-08-26
Ankylosing spondylitis (AS) is a prototypical axial spondyloarthritis (axSpA) defined by chronic inflammatory back pain, progressive spinal stiffness, and frequent extra-articular manifestations such as acute anterior uveitis (21%-33%), inflammatory bowel disease (5%-10%), and psoriasis (4%-13%). Management has shifted from non-steroidal anti-inflammatory drugs (NSAIDs) to highly targeted biologic and synthetic disease-modifying antirheumatic drugs (DMARDs). This comprehensive review focuses on the current evidence for biologic and targeted synthetic therapeutics in the management of AS, emphasizing mechanisms of action, regulatory approvals, dosing regimens, and clinical efficacy. Three major therapeutic classes are identified: two biologic DMARD classes, comprising tumor necrosis factor-alpha (TNF-α) inhibitors and interleukin-17 (IL-17) inhibitors, and the targeted synthetic DMARDs, namely, the Janus kinase-signal transducer and activator of transcription (JAK-STAT) inhibitors. TNF inhibitors (adalimumab, infliximab, etanercept, golimumab, certolizumab pegol) typically achieve Assessment of Spondyloarthritis International Society 40% improvement (ASAS40) rates of 40%-58% at 12-24 weeks versus 13%-24% with placebo, and maintain clinical benefit in many patients over 5-8 years. IL-17 inhibitors (secukinumab, ixekizumab, bimekizumab, brodalumab, netakimab) yield broadly similar ASAS40 responses (30%-50% versus 10%-20% placebo) and are particularly useful in patients with concomitant psoriasis with substantially reduced risk of tuberculosis reactivation. JAK inhibitors (tofacitinib, upadacitinib) represent the newest class, offering oral administration with ASAS40 responses of 40%-52% versus 13%-26% for placebo in both biologic-naïve and biologic-experienced AS, though cardiovascular safety considerations necessitate careful patient selection. Therapeutic selection should consider comorbidities (uveitis favors TNF monoclonal antibodies; psoriasis favors IL-17 inhibitors), safety profile, route of administration, and sequencing after non-steroidal anti-inflammatory drug failure. Understanding these pharmacological distinctions enables personalized therapeutic decisions based on the specific molecular pathology and risk profile of the individual patient.
Ameer OZ, Temsah R, Alsouss YO, Al-Amoudi R, Khanfar MA, Salman IM
IBD-associated Neoplasia (3 papers)
Peroxynitrite-activated near-infrared fluorescence sensing platform for early non-invasive IBD diagnosis, herbal formula efficacy evaluation and anti-enteritis bioactive components screening. Talanta | 2026-09-03
Inflammatory bowel disease (IBD) severely impairs patients’ quality of life and elevates colorectal cancer risk, where early diagnosis and timely intervention are vital to control disease remission. Peroxynitrite (ONOO-), a critical reactive nitrogen species closely involved in IBD pathogenesis, is an attractive biomarker for biological detection. Herein, we rationally constructed a turn-on near-infrared fluorescent probe HCY-PO targeting ONOO-. Upon ONOO–triggered cleavage of the diphenylphosphinamide recognition group, HCY-PO exhibited a distinct fluorescence enhancement at 750 nm within 60 s, with a detection limit of 90 nM and strong anti-interference capability in complex biological systems. Using HCY-PO, we achieved real-time tracking of endogenous ONOO- fluctuations in inflamed NCM460 cells, zebrafish enteritis models, and early diagnosis of ulcerative colitis in mouse models. Importantly, the probe’s fluorescent signal intensity was positively correlated with IBD severity. Moreover, HCY-PO achieved the sensitive detection of ONOO- in mouse feces, enabling non-invasive monitoring of IBD progression. Based on this superior analytical performance, an integrated fluorescence sensing platform was first established to semi-quantitatively evaluate the therapeutic efficacy of the traditional Chinese medicine formula Bu-Zhong-Yi-Qi-Tang. Consistent results among fluorescence, pathology and inflammatory factor tests verified the method reliability, and five anti-enteritis bioactive constituents from the formula were efficiently screened via this platform. Collectively, this work provides a powerful analytical tool for non-invasive early IBD diagnosis, drug efficacy evaluation, and rapid screening of anti-enteritis bioactive components.
Hu L, Li T, Zeng S, Ouyang J, Huang S, Sun D, Yang Z, Wang Q, Yao Z, Li CY
Diagnostic Performance and Reproducibility of Chromoendoscopic Classification (FOCUS Classification: Flat-Type Dysplasia Optical Assessment by Chromoendoscopy in Ulcerative ColitiS) for Flat-Type Dysplasia in Ulcerative Colitis-Associated Neoplasia. Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society | 2026-09
Ulcerative colitis-associated neoplasia (UCAN) often presents as flat-type dysplasia that is difficult to characterize endoscopically. We developed a FOCUS (Flat-type dysplasia Optical assessment by Chromoendoscopy in Ulcerative colitiS) classification and evaluated its diagnostic performance and reproducibility. This single-center retrospective study included 33 UCAN lesions from 26 patients. Prospectively recorded FOCUS classifications at 230 biopsy sites were compared with histopathology. Chromoendoscopic patterns were categorized as Type I (“suggestive of non-dysplasia,”), Type II (“suggestive of dysplasia with low confidence”), or Type III (“suggestive of dysplasia with high confidence”). Diagnostic performance was assessed using two prespecified thresholds: Types II/III versus Type I and Type III versus Types I/II. Eight endoscopists independently classified all images; interobserver and intraobserver agreement were assessed using Fleiss’ and Cohen’s κ, respectively. The dysplasia-bearing rate increased stepwise from Type I to Type III (Type I 15.5%, Type II 58.3%, Type III 81.8%). Using the primary threshold, sensitivity was 82.0%, and specificity 75.4% (positive likelihood ratio 3.33; negative likelihood ratio 0.24). Interobserver agreement for the three-category classification was moderate to substantial (Fleiss’ κ 0.629; 95% CI 0.545-0.712), and median intraobserver agreement was substantial (Cohen’s κ 0.738). The FOCUS classification provides clinically meaningful risk stratification for flat-type dysplasia in a high-risk UCAN cohort, with acceptable interobserver and intraobserver reproducibility.
Takabayashi K, Murata S, Sasaki M, Miyazaki K, Masunaga T, Kirita K, Mizutani M, Yoshimatsu Y, Takatori Y, Akimoto T
FOXP3 Stability-Adaptation Paradox: Reshaping Treg-Based Therapies for Intestinal Diseases.Review International journal of biological sciences | 2026-08-21
Regulatory T cells (Tregs) maintain intestinal immune homeostasis, but their therapeutic potential is constrained by a fundamental paradox: the same plasticity that enables tissue repair renders FOXP3 vulnerable to degradation in chronic inflammation. Mechanistically, microbial metabolites (short-chain fatty acids, bile acids) and retinoic acid stabilize FOXP3 and induce RORγt⁺/GATA3⁺ Treg specialization. In contrast, inflammatory cytokines and succinate accumulation drive ER stress and post-translational FOXP3 degradation, leading to lineage instability in inflammatory bowel disease, colorectal cancer, and celiac disease. Current Tregs-based therapies-adoptive transfer, low-dose IL-2, CAR-Tregs, and microbiota consortia-have demonstrated safety profiles yet exhibit limited efficacy due to this inherent instability. Next-generation strategies therefore focus on actively stabilizing FOXP3 (e.g., gut-restricted HDAC inhibitors) and engineering exhaustion-resistant CAR-Tregs. Three questions remain for clinical translation: how to preserve Treg stability without compromising anti-tumor immunity; which biomarkers (succinate, TSDR methylation, FOXP3Δ2/FL ratio) predict response; and whether logic-gated CAR-Tregs can overcome exhaustion. Addressing these challenges will enable the development of precision Treg immunotherapy for intestinal diseases.
Ren Y, Liu X, Wang B, Yin H, Zhao J, Xin S, Wang H, Zhang Y, Liu X, Liu J
Pregnancy & Reproductive Health (3 papers)
Perinatal exposure to nano-polystyrene: deleterious imprinting on inflammatory bowel diseases. Particle and fibre toxicology | 2026-09-10
The extent of production and use of plastics leads to release of nanoplastics (NPL) into the environment, where they undergo weathering that could alter their toxicological properties. NPL enter the human food chain via contaminated food, and food packaging, and within the body they are known to pass through epithelial barriers. In parallel to the increasing exposure to plastics, the incidence of non-communicable diseases, including intestinal diseases, is rising worldwide. This study focuses on how oral exposure of gestating and lactating female mice to 50 nm polystyrene beads, pristine (PS50) or weathered (PS50w) affects intestinal function in offspring. Two aspects of intestinal function were studied: oral tolerance and the onset of intestinal disorders. Gestating mice received 1.25 mg of PS50 or PS50w by oral gavage administered daily from gestational day 15. Exposure was continued during lactation until pups were weaned (Postnatal Day, PND21). To study oral tolerance, offspring were exposed to ovalbumin (OVA) both orally and systemically. To study intestinal disorders, colitis was induced by exposure to Dextran Sulfate Sodium (DSS) from PND63. Perinatal exposure to PS50 or PS50w had no impact on mortality of gestating or lactating dams or sex ratio in litters, but did lead to increased body weight at PND63 in offspring. No impact on tolerance to OVA was observed. However, macroscopic scores for DSS-induced colitis in adult offspring were significantly worsened in both sexes. In this context, in male offspring, PS50w was more deleterious than PS50. Early-life exposure to PS50 or PS50w has long-lasting consequences on gut physiology, and effects show sexual dimorphism. The results presented raise questions on the kinetics of later-life effects linked to perinatal PS50 and PS50w exposure, and introduce the notion of imprinting.
Airaud M, Roldan A, Le Cléac’h J, Isoard L, Carrière M, Ménard S, Barreau F
Evaluating embryo euploidy among patients diagnosed with inflammatory bowel disease undergoing in vitro fertilization. Minerva obstetrics and gynecology | 2026-09-07
The impact of inflammatory bowel disease (IBD) on embryo chromosomal competence during in vitro fertilization (IVF) remains poorly defined. This study aimed to evaluate embryo euploidy rates among patients with IBD undergoing IVF with preimplantation genetic testing for aneuploidy (PGT-A), compared with patients without IBD. This retrospective cohort study was conducted at an urban, academic reproductive medicine center. A total of 43 patients with IBD (Crohn’s disease or ulcerative colitis) and 129 matched controls without IBD who underwent IVF with PGT-A between 2011 and 2022 were included. Patients with endometriosis, severe male factor infertility, prior chemotherapy or radiation exposure, or chromosomal translocations were excluded. All patients underwent controlled ovarian hyperstimulation, oocyte retrieval, intracytoplasmic sperm injection, and trophectoderm biopsy with PGT-A using next-generation sequencing. The primary outcome was euploid blastocyst rate. Secondary outcomes included oocyte yield, oocyte maturity and fertilization rates, blastulation rate, and rates of aneuploid and mosaic embryos. Euploid blastocyst rates were identical between patients with and without IBD (47.5% vs. 47.5%, P=0.99), with no significant differences in aneuploid or mosaic embryo rates. Patients with IBD had significantly higher total and mature oocyte yields despite comparable baseline ovarian reserve parameters. No differences were observed in oocyte maturity, fertilization, or blastulation rates. Results remained unchanged after multivariate adjustment. In this cohort, patients with IBD undergoing IVF with PGT-A had euploid blastocyst rates similar to those without IBD, suggesting no clear impact on embryo chromosomal competence. However, given the retrospective design and small sample size, these findings should be interpreted with caution, and a modest effect cannot be excluded. Overall, the results provide some clinical reassurance and support ART as a reasonable option for patients with IBD, while underscoring the need for prospective studies to further evaluate disease-related factors.
Ghofranian A, Estevez SL, Shaari DS, Alkon-Meadows T, Hernandez-Nieto C, Baird M, Lee JA, Copperman AB, Friedenthal J
Pregnancy safety of biologics in inflammatory bowel disease: A systematic review and network meta-analysis. Therapeutic advances in gastroenterology | 2026-09-03
Biologic safety during pregnancy in patients with inflammatory bowel disease (IBD) remains a clinical concern, particularly with the increasing use of novel agents such as ustekinumab (UST) and vedolizumab (VDZ). A network meta-analysis (NMA) was performed to compare pregnancy-related outcomes among various biological agents and nonbiologic-exposed patients. Systematic review and frequentist random-effects NMA of comparative observational studies. This study systematically searched from inception to 23 March 2025 for comparative studies reporting pregnancy outcomes in biologics or conventional therapies (CT)-exposed patients with IBD. Outcomes included preterm birth, congenital malformation (CM), low birth weight (LBW), and spontaneous abortion. An NMA model was applied. Subgroup analysis was conducted for studies with comparable baseline disease activity between the treatment groups. This NMA included 12 studies. Anti-tumor necrosis factor alpha (TNF-α) agents were not associated with an increased risk of any adverse pregnancy outcomes. UST and VDZ were associated with increased CM risks (UST: odds ratio [OR]: 2.32 [1.31-4.10]; VDZ: OR: 1.98 [1.11-3.52]), and VDZ was associated with LBW (OR: 2.17 [1.15-4.11]). These associations were not significant in the subgroup analyses limited to studies with similar disease activity. Sensitivity analysis revealed that a single important study influenced the CM risk of UST/VDZ, whereas the LBW risk with VDZ remained consistent. This is the first NMA to comprehensively assess the pregnancy-related safety of biologic therapies, including the novel biologics VDZ and UST, in patients with IBD. Anti-TNF agents have the most robust pregnancy safety evidence and were not associated with an increased risk of adverse pregnancy outcomes in this analysis. The findings for UST and VDZ should be framed as exploratory and potentially affected by residual confounding, as the observed risk signals were not consistently maintained in the additional analyses. INPLASY202540012. Women with inflammatory bowel disease (IBD) are often diagnosed during their reproductive years, and many require ongoing treatment during pregnancy to keep their disease under control. Biologic therapies are commonly used to treat IBD, but concerns remain about their safety for both mothers and babies. In this study, we included 12 studies involving more than 6,600 pregnancies and focused on outcomes including premature birth, congenital malformations (CM), low birth weight (LBW), and spontaneous abortion. Overall, women who received anti-TNF biologic therapies did not have a higher risk of adverse pregnancy outcomes than women who did not receive biologic treatment. Evidence for the newer biologic medicines ustekinumab and vedolizumab remains limited, and our findings for these two drugs should be considered exploratory rather than conclusive. In the overall analysis, both appeared to be associated with a higher risk of CM, while vedolizumab also appeared to be associated with LBW. However, these signals were no longer observed when we limited the analysis to studies in which disease activity was similar between treatment groups. Because newer biologics may be likely to be given to women with more severe disease or to those who have not responded to previous treatments, the differences we observed may reflect disease severity, treatment history, or other factors that we could not measure. For the same reason, any comparison or ranking of biologic therapies in this analysis should be regarded as exploratory and hypothesis-generating only, rather than as a definitive ranking of which drug is safest during pregnancy. Our findings highlight the importance of maintaining good disease control during pregnancy, because active IBD itself is an important risk factor for adverse pregnancy outcomes. Further large, well-designed prospective studies are needed before the pregnancy safety of newer biologic medicines can be established with greater certainty.
Huang CW, Yen HH, Chen YY, Su PY, Lin YC
Intestinal Ultrasound (IUS) (2 papers)
Association Between Bowel Urgency and Intestinal Ultrasound Parameters in Ulcerative Colitis: Insights Into Transmural Inflammation and Symptom Pathophysiology.★ United European gastroenterology journal | 2026-09
Bowel urgency (BU) is a key symptom of ulcerative colitis (UC), often impairing the quality of life. This study aimed to identify intestinal ultrasound parameters associated with BU, given that UC may also have transmural involvement, and compare these with endoscopic activity and biomarkers. In this single-centre prospective study, UC patients undergoing colonoscopy between January 31 and September 27, 2023 were enrolled. Transabdominal and transperineal ultrasound were performed to evaluate bowel wall thickness (BWT), including individual layers (mucosa, submucosa, and muscularis propria), and colour Doppler signal (CDS) in the sigmoid colon and rectum. BU was defined according to the Simple Clinical Colitis Activity Index urgency subscore. Of 59 patients, 33 (56%) reported BU. Compared with those without BU, patients with BU had significantly higher C-reactive protein, Mayo Endoscopic Subscore (MES), BWT (descending colon, sigmoid colon, rectum), CDS (sigmoid colon, rectum), and submucosal and muscularis propria thickness in the sigmoid colon (all p < 0.05). Mucosal thickness and faecal calprotectin were not significantly different (p = 0.11 and p = 0.48, respectively). In MES-adjusted logistic regression, submucosal (p < 0.01) and muscularis propria (p = 0.03) thickness remained associated with BU, whereas mucosal thickness did not (p = 0.97). Receiver operating characteristic analysis showed that sigmoid submucosal thickness had greater diagnostic accuracy than mucosal thickness (AUC 0.77 vs. 0.62, p < 0.05). Sigmoid submucosal thickening was associated with BU and suggests that transmural inflammation may contribute to symptom pathophysiology. UMIN000050099.
Serizawa K, Sagami S, Umeda S, Asonuma K, Komatsu M, Shibui S, Maeda M, Nogami A, Karashima R, Nakano M
Evaluation of Super-Resolution Contrast-enhanced US in Crohn Disease Activity Assessment.★ Radiology | 2026-09
Background Measurement of Crohn disease (CD) activity is crucial for guiding treatment decisions. Super-resolution contrast-enhanced US (SRCEUS) is an emerging technique that can be used to assess vascularity at micrometer scale; however, its performance in differentiating CD activity stages is not yet known. Purpose To evaluate SRCEUS in the assessment of disease activity in participants with CD. Materials and Methods This prospective study included participants with CD involving the terminal ileum or colon who underwent intestinal SRCEUS imaging between January 2025 and June 2025. Participants were classified into remission/mild or moderate/severe activity groups based on the Simple Endoscopic Score for Crohn’s Disease. B-mode US, color Doppler flow imaging (CDFI), conventional contrast-enhanced US (CEUS), and SRCEUS were performed. SRCEUS parameters were calculated. Logistic regression modeling, receiver operating characteristic analysis, and the DeLong test were used to evaluate and compare diagnostic performance. Results This study included 54 participants (mean age, 30 years ± 8.5 [SD]; 42 men). Key SRCEUS vascular parameters were higher in the moderate/severe activity group than the remission/mild activity group, including maximum density (mean, 63.4 ± 13.1 vs 51.1 ± 15.6; P = .003), mean density (mean, 26.9 ± 5.3 vs 21.1 ± 8.0; P = .007), mean velocity (mean, 40.2 mm/sec ± 27.3 vs 23.0 mm/sec ± 14.9; P = .01), vascular density ratio (mean, 73.2% ± 12.8 vs 38.5% ± 17.8; P < .001), and fractal dimension (mean, 1.7 ± 0.1 vs 1.5 ± 0.1; P < .001). SRCEUS performed well in distinguishing participants with remission/mild activity from those with moderate/severe activity (area under the receiver operating characteristic curve [AUC], 0.92; sensitivity, 94.1%; specificity, 95.0%). SRCEUS performed better than conventional CEUS (AUC, 0.78; P = .03). Clinical, B-mode US, CEUS, and SRCEUS parameters were included in a combined model, in which the International Bowel Ultrasound Segmental Activity Score and vascular density ratio were identified as influential factors. The combined model had an AUC of 0.94, demonstrating superior performance to both CDFI (AUC, 0.82; P = .04) and conventional CEUS (P = .002) and similar performance to SRCEUS (P = .51). Conclusion SRCEUS demonstrated excellent performance in differentiating CD activity through high-resolution depiction of microstructural changes, with superior performance to conventional CEUS. © RSNA, 2026 Supplemental material is available for this article. See also the editorial by Katwal and Chernyak in this issue.
Aihemaiti S, Li M, Xu M, Mao R, Xie X, Chen Y
Nutrition & Lifestyle (2 papers)
Negotiating Medication Adherence in Everyday Life with Inflammatory Bowel Disease: A Qualitative Study. Patient preference and adherence | 2026-09-01
Inflammatory bowel disease (IBD), including Crohn’s disease, ulcerative colitis, and IBD unclassified, is a chronic condition that can affect daily life. Maintenance therapy is essential, yet non-adherence remains common and may compromise treatment outcomes. This study aimed to explore how adults with IBD understand, negotiate, and enact medication adherence as part of everyday self-care. Inductive, qualitative, semi-structured interviews were conducted with adults diagnosed with IBD at a gastroenterology clinic in Sweden. Interviews were audio-recorded, transcribed verbatim, and analysed using content analysis. Fifteen interviews were conducted (9 ulcerative colitis, 5 Crohn’s disease, 1 IBD-U). Three main categories were identified: illness perceptions, healthcare perceptions, and treatment perceptions. Medication adherence was described as an ongoing process shaped by how participants interpreted symptoms, adapted to life with IBD, and evaluated the need for treatment. Participants weighed the perceived benefits of medication against concerns about adverse effects and often combined medical treatment with lifestyle-based strategies for symptom management. Trusting communication, continuity of care, and access to relevant information facilitate adherence, while practical treatment burdens and uncertainty regarding disease activity undermined adherence. Medication adherence in IBD is embedded within everyday self-care and influenced by illness perceptions, treatment beliefs, practical challenges, and healthcare encounters. Clinicians should acknowledge patients’ concerns, dietary practices, and lifestyle strategies alongside medical treatment. Person-centred communication, clear treatment goals, and shared decision-making may support adherence and strengthen self-care. Many people with inflammatory bowel disease (IBD) do not take their medication as prescribed, despite the importance of treatment for preventing disease flare-ups and maintaining remission. Previous research has identified several reasons for non-adherence but less is known about how patients themselves understand and manage medication use in everyday life. We explored how people with IBD think about their medication, illness, and the healthcare. We interviewed 15 adults with IBD and analysed their experiences.Participants described medication adherence as part of a broader process of managing daily life with a chronic illness. Their decisions about taking medication were influenced by: How they understood and interpreted their symptoms.Acceptance of diagnosis and its long-term consequences.How they weighed benefits of medication against concerns.Concerns about side effects.Practical challenges such as multiple daily doses, large tablets, treatment costs.Experiences of communication with healthcare professionals.Some patients preferred to rely partly on lifestyle changes, such as stress reduction, physical activity, or dietary adjustments. Trustful communication and clear information from the IBD care team were described as important for supporting medication use. Medication adherence is not simply a matter of remembering to take tablets. It is closely connected to how people understand their illness, evaluate treatment, and manage everyday life with IBD. Healthcare professionals can support adherence by providing clear information, addressing patients’ concerns, and building a trusting relationship that encourages shared decision-making.
Ljungström E, Hjortswang H, Eberhardson M, Pihl Lesnovska K
Glucagon like peptide 1 receptor agonists in patients with inflammatory bowel disease: safety, clinical effectiveness and anti-inflammatory mechanisms.Review Frontiers in gastroenterology (Lausanne, Switzerland) | 2026-08-21
The prevalence of obesity among patients with inflammatory bowel disease (IBD) continues to rise and is associated with adverse IBD outcomes and diminished treatment response. This study reviews the clinical safety and efficacy of glucagon-like peptide-1 receptor agonists (GLP-1RA) in patients with IBD and comorbid obesity and explores their theorized anti-inflammatory mechanisms. Published articles through July 2026 were identified via a PubMed search for a narrative review using terms related to GLP-1RA, IBD, safety, effectiveness, and outcomes. Data extraction focused on GLP-1RA intervention details, IBD-related outcomes and inflammatory markers, and proposed anti-inflammatory mechanisms. GLP-1RA therapy promotes weight loss in patients with IBD comparable to the general population (about 16 pounds over 18 months). The most frequently reported adverse effects are gastrointestinal, often limiting treatment continuity. Most studies report no significant differences in hospitalization, surgery, steroid use or IBD medication adjustments, and some reported improvement in these outcomes. Data on endoscopic disease activity is limited. Inconsistent effects of GLP-1RA on inflammatory serum biomarkers were noted, with reductions in CRP but no consistent changes in fecal calprotectin. Addressing obesity in patients with IBD is an emerging clinical priority. GLP-1RA therapy demonstrates efficacy in promoting weight loss, improving glycemic control, and reducing systemic inflammation, which may benefit IBD disease activity. Longitudinal studies are required to clarify the long-term impact of GLP-1RA on clinical and endoscopic outcomes in IBD.
Fernando S, Zhao J, Josloff K, Zubair N, Desai A, Shivashankar R, Kozuch PL, Choudhary C, Lichtenstein G, Sehgal P
Genetics & Genomics (1 papers)
The impact for causal associations between common diseases and inflammatory bowel disease: a disease-wide bidirectional Mendelian randomization study. Inflammation research : official journal of the European Histamine Research Society … [et al.] | 2026-09-05
Observational studies on associations between various diseases and inflammatory bowel disease (IBD) are often limited by confounding and reverse causation. We aimed to assess potential causal relationships between a wide range of diseases and IBD, including Crohn’s disease (CD) and ulcerative colitis (UC). We performed a comprehensive bidirectional Mendelian randomization (MR) analysis of 104 common diseases and IBD traits using the generalized summary-data-based MR (GSMR) approach. Genome-wide association study (GWAS) summary statistics for diseases were obtained from the MRC Integrative Epidemiology Unit, and IBD data from the International IBD Genetics Consortium. Summary-data-based MR (SMR) integrating GWAS and expression quantitative trait locus data was applied to identify pleiotropic genes associated with IBD. MR analyses identified 38, 34, and 52 exposures significantly associated with IBD, UC, and CD, respectively. Childhood- and adult-onset asthma showed distinct causal effects on UC and CD. Reverse MR indicated associations between IBD traits and 15 diseases, including multiple sclerosis. SMR identified RGS14 and CARD9 as pleiotropic genes linked to IBD, suggesting shared genetic mechanisms with asthma and multiple sclerosis. These findings provide evidence for causal links and shared immune-related genetic mechanisms underlying IBD, highlighting potential targets for future research.
Sun Y, Liang Z, Ou Z, Gao L, Wang YF, Yuan J, Yu G, Sun R
Guidelines & Consensus (1 papers)
Strengthening the Methodological Rigor of the APAGE Clinical Practice Guideline on Small Molecules and IL-23 p19 Inhibitors for Inflammatory Bowel Disease.Letter Journal of gastroenterology and hepatology | 2026-09-04
Category Distribution
TipWant More Control?
The Interactive Dashboard lets you filter and search across all categories, download results as CSV or Excel, and explore the full 30-day backlog - useful if you missed a week or want to search by keyword across a wider date range.
Subscribe via RSS to get daily updates automatically, or use the per-category feeds to follow just one subfield.