IBD Literature Report
Coverage: May 04, 2026 - May 11, 2026
122
Papers This Week
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Microbiome & Immunology (18 papers)
Snake Gut Microbiota as a Source of Anti-Inflammatory Probiotics: Isolation and Functional Characterization of Two Novel Strains. Integrative zoology | 2026-05-09
The intestinal microbiome is fundamental to host physiological homeostasis, while deviations from its balanced state have been linked to inflammatory bowel diseases (IBD). To address the limitations of conventional antibiotic therapies, this study explored snake gut microbiota as a novel source of anti-inflammatory probiotics. We explored the gut microbiota of five snake species (Deinagkistrodon acutus, Trimerodytes annularis, Trimerodytes percarinatus, Lycodon rufozonatus, and Trimeresurus stejnegeri) through metagenomic sequencing. Community composition analysis revealed that the phylum-level composition was mainly Proteobacteria, Bacteroidetes, Actinomycetota, and Firmicutes. We further detected some potential probiotic species, such as Enterococcus, Lactobacillus, and Limosilactobacillus. From 196 isolated strains, Lactobacillus johnsonii DA0116 and Limosilactobacillus reuteri DA0218 were selected through rigorous safety and functional assessments, including acid/bile tolerance, pathogen inhibition, and adhesion capacity. In a DSS-induced murine colitis model, both strains significantly reduced disease activity index (DAI), pro-inflammatory cytokines (TNF-α, IL-6, and IL-8), and restored gut microbiota diversity. Additionally, whole-genome analysis identified bacteriocin synthesis clusters (gassericin-S/T) and carbohydrate metabolism genes, explaining their antimicrobial and immunomodulatory properties. This study not only emphasizes the untapped latent value of reptilian gut microbiota for probiotic discovery but also provides two candidate strains with therapeutic promise for IBD and functional food applications.
Kang X, Hu L, Song J, Zhang Z, Li Y, Zhang Q, Luo C, Pang Y, Guo P, Yue B
The gut microbiome: Recent findings and future opportunities in cystic fibrosis.Review Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society | 2026-05-09
The gut microbiome is a key modulator of human health throughout life, from infancy to old age. Within this relatively young field, microbiome characteristics are being utilized as useful clinical endpoints and indicators of health. Moreover, microbiome-based interventions have been developed to modulate the gut microbiome to ameliorate a range of disorders, including inflammatory bowel disease, obesity, and diabetes. Conversely, there is a paucity of knowledge on the cystic fibrosis (CF) gut microbiome, despite its obvious importance in gastrointestinal (GI) symptoms in this disorder. In this short review we focus on recent findings in CF gut microbiome research and draw upon advances and knowledge from the wider field of gut microbiome research. We recommend increased efforts to improve our understanding of the CF gut microbiome, with knowledge transfer from the field of gut microbiome research being a pragmatic approach to both guiding and providing novel interventions to manage and improve CF GI pathophysiology and associated comorbidities.
Marsh R, Tricker JM, Delhaes L, Bomberger JM, van der Gast C
Clinical combination therapy for IBD and promising co-delivery strategies.Review Inflammopharmacology | 2026-05-08
Biological agents are the cornerstone of first-line treatment for inflammatory bowel disease. However, approximately 33% of patients either fail to respond initially or experience diminished efficacy over time. The use of combination therapies, such as pairing biological agents with immunomodulators or small-molecule drugs, has proven effective in enhancing efficacy and mitigating resistance. For instance, the combination of infliximab and azathioprine elevated corticosteroid-free clinical remission and mucosal healing rates in patients with ulcerative colitis to 39.7 and 62.8%, respectively; triple therapy with vedolizumab, adalimumab, and methotrexate raised the week 10 clinical remission rate in patients with Crohn’s disease to 61.8%; and combining guselkumab with golimumab increased the response rate in patients with ulcerative colitis to 83%. Despite these successes, challenges remain in optimizing dosing regimens and managing systemic toxicities. Nanocarriers offer a solution by encapsulating one or more drugs within a single system, facilitating targeted delivery, simplifying treatment protocols, and minimizing toxicity. Research indicates that advanced delivery systems, including poly(lactic-co-glycolic acid) nanoparticles, mulberry leaf liposomes, and sodium alginate hydrogels, can enhance anti-inflammatory effects, promote mucosal healing, and modulate the gut microbiota, providing effective colitis treatment. This review examines combination dosing strategies for inflammatory bowel disease, nanodelivery methods, and novel approaches to advance the clinical application of nanodelivery technology in combination therapies.
Wang X, Xu W, Wu Y, Liu P, Wang B, Li J, Dai H
Restoring immunoglobulin A/polymeric immunoglobulin receptor transport axis for the oral treatment of inflammatory bowel disease.★ Journal of controlled release : official journal of the Controlled Release Society | 2026-05-08
The immunoglobulin A/polymeric immunoglobulin receptor (IgA/pIgR) transport axis orchestrates mucosal immunity, epithelial integrity, and microbiota homeostasis, and its dysregulation promotes the development and progression of inflammatory bowel disease (IBD). However, therapeutic strategies aimed at restoring this axis remain underdeveloped. In this study, we developed an innovative oral therapy utilizing hybrid extracellular vesicles to specifically modulate the IgA/pIgR transport axis for IBD treatment. Our findings demonstrate that this oral targeting strategy effectively upregulates epithelial pIgR expression and increases the transport of dimeric IgA into intestinal lumen, thereby integrating immune regulation, epithelial barrier repair, and microbiota remodeling. This approach successfully treated DSS-induced colitis, restoring multiple disease parameters to levels comparable to those observed in healthy mice. Collectively, this work provides the first evidence for the therapeutic benefit of selectively restoring the IgA/pIgR transport axis in IBD via the oral route.
You X, Ma J, Zou L, Shu Y, Jia Z, Kang Y, Wang Y, Xiao X, Ma Z, He J
Research of heat-killed Loigolactobacillus coryniformis NA-3 and Lactiplantibacillus plantarum NA as potential substitutes for live strains in immune regulation and anti-inflammatory effects. World journal of microbiology & biotechnology | 2026-05-08
The safety of live probiotics remains debated due to concerns regarding their viability and functional efficacy under harsh in vivo and in vitro conditions. Inflammatory bowel disease (IBD) is a complex disease stemming from various factors. It has been reported that probiotics shows anti-inflammatory function. This study evaluated the immunomodulatory and anti-inflammatory properties of heat-killed Lactobacillus strains (a form of postbiotics). Because viable Loigolactobacillus coryniformis NA-3 exhibited lower in vitro viability than Lactiplantibacillus plantarum NA, we first evaluated the phagocytic activity and TLR2-mediated immunoregulatory effects of heat-killed L. coryniformis NA-3 in RAW 264.7 cells, and conducted a preliminary comparative assessment of both live and heat-killed L. coryniformis NA-3 in murine models. We further investigated two distinct heat-killed strains: L. coryniformis NA-3 and Lactiplantibacillus plantarum NA. Heat-killed L. coryniformis NA-3 induced TLR2-dependent immunomodulatory effects in vitro and showed effects comparable to those of its live counterpart in vivo under the conditions tested. Both heat-killed strains were associated with changes in inflammatory markers, including decreased levels of pro-inflammatory cytokines (IL-6, TNF-α) and increased levels of anti-inflammatory mediators (IL-4, IL-10, TGF-β) in mice. In addition, they were associated with alterations in antioxidant parameters, including changes in SOD, GSH-Px, GR, NQO1, HO-1, Nrf2, and MDA levels, as well as increased expression of the tight junction proteins claudin-1 and occluding. Observations from this study are consistent with the potential involvement of the TLR2/NF-κB p65 signaling pathway. These findings highlight the potential of heat-killed probiotics as safe and effective alternatives to live strains in immune regulation and anti-inflammation.
Xu X, Tian D, Qiao Y, Peng Q, Ran C, Yang Y, Zhang Z, Yao Y, Ding Q, Zhou Z
Selenized Probiotic L. brevis 23017 Alleviates Colitis by Modulating the Nrf2-GPX4 Axis to Inhibit Ferroptosis. Biological trace element research | 2026-05-07
Ulcerative colitis (UC) constitutes a principal subtype of inflammatory bowel disease (IBD) and exhibits escalating global incidence. This study elucidates the therapeutic efficacy and mechanistic basis of novel selenized probiotic, Lactobacillus brevis 23017 (Se-Lb23017), and biogenic selenium nanoparticles (SeNPs) in a dextran sodium sulfate (DSS)-induced colitis murine model. The investigation specifically probed ferroptosis inhibition and activation of the Nrf2-GPX4-HO-1 signaling axis. The results demonstrated 80 µg/mL of Na2SeO3 is optimal for preparing Se-Lb23017. Both Se-Lb23017 and SeNPs exhibited typical morphology under scanning electron microscopy (SEM). In vivo experiments showed that administration of either Se-Lb23017 or SeNPs, especially Se-Lb23017 effectively mitigated key features of colitis, including elevated disease activity index (DAI) scores, weight loss, tissue damage, and colon shortening. In vitro, both Se-Lb23017 and SeNPs, especially Se-Lb23017 significantly reduced the expression of pro-inflammatory mediators (TNF-α, IL-1β, IL-6) and enhanced levels of anti-inflammatory cytokine IL-10. Mechanistically, the protective effects were associated with reduced oxidative stress and ferroptosis suppression via Nrf2-GPX4-HO-1 axis activation and subsequent reduction in lipid peroxidation. Collectively, these findings demonstrate that Se-Lb23017 and SeNPs ameliorate experimental colitis through synergistic anti-inflammatory and antioxidant effects, providing cytoprotection via Nrf2-dependent ferroptosis inhibition. This study highlights selenized probiotics as a promising therapeutic strategy for ulcerative colitis by targeting a novel cell death modality.
Zhuang Y, Liu Q, Shi F, Kong R, Ma C, Ma D
Ovotransferrin Alleviates Ulcerative Colitis by Modulating Ligilactobacillus murinus-Mediated Bile Acid Metabolism via the Ptgs2/JAK-STAT Signaling Axis. Journal of agricultural and food chemistry | 2026-05-07
Ovotransferrin (OVT) is a functionally active protein demonstrated to alleviate ulcerative colitis (UC), although its mechanism remains incompletely understood. Notably, UC is closely associated with dysbiosis of the gut microbiota. This study investigates the potential of OVT to alleviate colitis by reshaped gut microbiota composition in a DSS-induced UC mouse model. Specifically, Ligilactobacillus murinus (L. murinus) was isolated from the gut microbiota of OVT-treated UC mice and stimulated by OVT in vitro. Integrated whole-genome sequencing and targeted metabolomics revealed that L. murinus encodes bile salt hydrolase, thereby driving secondary bile acid biosynthesis. Mechanistically, fermentation products (FP) derived from coculture of L. murinus with bile exerts potent anti-inflammatory in both Caco-2 cells and a colitis model by Ptgs2 (COX-2) downregulation and the JAK-STAT signaling pathway inhibition. These results established the “OVT-L. murinus-bile acids-Ptgs2/JAK-STAT” axis as a novel mechanism for UC treatment, providing a foundation for high-value applications of OVT in functional foods.
Zheng D, Xin X, Ouyang H, Ma L, Wang H, Liu X, Liao X, Chu X, Gao Y, Huo J
Genome-wide sweeps create ecological units in the human gut microbiome. Nature | 2026-05-06
The human gut microbiome is shaped by diverse selective forces that originate from host and environmental factors and it substantially influences health and disease. Whereas the association of microbial lineages with various health conditions has been shown at different taxonomic levels1-5, the extent to which unifying adaptive mechanisms sort microbial lineages into ecologically differentiated populations remains poorly understood. Here we show that genome-wide selective sweeps are a pervasive mechanism that differentiates bacteria in the microbiome. This mechanism leads to population structures akin to global epidemics across geographically and ethnically diverse human populations. Such sweeps arise when an adaptation allows a clone to outcompete others in its niche followed by rediversification, and they manifest as clusters of closely related genomes on long branches in phylogenetic trees. This structure is revealed by excluding recombination events that mask the clonal descent of the genomes. Indeed, we show that genome-wide sweeps originate under a wide range of recombination rates in at least 66 taxa from 25 bacterial families. Estimated ages of divergence suggest that sweep clusters can spread globally within decades and that this process has occurred throughout human history. Sweep clusters are associated with different host conditions-such as age, colorectal cancer, inflammatory bowel diseases and type 2 diabetes-as an indication of their ecological differentiation. Our results reveal an evolutionary mechanism for the observation of stably inherited strains with differential associations and provide a theoretical foundation for analysing adaptation among microbial populations.
Yu XA, Strachan CR, Herbold CW, Lang M, Gasche C, Makristathis A, Segata N, Pollak S, Tett A, Polz MF
OTOP2 Proton Channel Couples Luminal pH Sensing to Intestinal Immune Homeostasis. The Journal of biological chemistry | 2026-05-06
Extracellular acidification is a hallmark of the inflamed intestinal tract in individuals with inflammatory bowel disease (IBD). The proton channel Otopetrin-2 (OTOP2), which is enriched in intestinal tissues, becomes dysregulated during inflammation. However, the specific role of OTOP2 in IBD pathogenesis remains unclear. In this study, we demonstrate a significant reduction of OTOP2 mRNA and protein in the inflamed mucosa of pediatric IBD patients, which inversely correlates with disease progression. Otop2 knockout (Otop2-/-) mice exhibit growth retardation and heightened susceptibility to intestinal inflammation, which is linked to intestinal pH dysregulation, altered gut microbiota composition, and compromised tight junction integrity. Accordingly, Otop2-/- mice exhibit increased susceptibility to dextran sulfate sodium (DSS)-induced colitis. Mechanistically, Otop2 deficiency reduces Paneth cell numbers and diminishes antimicrobial factor expression, likely due to impaired autophagy-lysosomal processes within these cells. Similarly, Otop2 deficiency impairs phagocytic function in bone marrow-derived macrophages (BMDMs). Together, these findings establish OTOP2 as a critical, pH-sensitive regulator of intestinal homeostasis and highlight its potential as a therapeutic target in IBD.
Yan W, Wang Y, Zhao H, Peng S, Lu Y, Wu B, Xiao Y
Cytotoxic CD4+ T cells and their implication in oral diseases and systemic diseases with oral manifestations.Review International immunopharmacology | 2026-05-06
T cells are derived from multipotent stem cells in the bone marrow and migrate to the thymus, where they differentiate into two main subpopulations: CD4+ T cells and CD8+ T cells. It is usually believed that CD4+ T cells mainly play a supplementary function in immune processes such as antibody production, antigen-specific CD8+ T cell activation, and immune regulation; whereas CD8+ T cells are able to kill the target cells through cell killing mechanism, and play an important role in the immune defense against intracellular pathogens and tumor immunity. A unique cytotoxic subpopulation of CD4+ T cells, designated CD4+ cytotoxic T lymphocytes (CD4+ CTLs), has emerged as a significant focus of research in recent years. This review focuses on biological properties and mechanisms of CD4+ CTLs, as well as the research progress of CD4+ CTLs in oral diseases and systemic diseases with oral manifestations, including Sjögren’s syndrome, IgG4-related disease, HIV infection, and inflammatory bowel disease, with the aim of elucidating the contributions of CD4+ CTLs to disease pathogenesis and uncovering novel therapeutic targets for these conditions.
Huang XX, Hu ST, Zhou G, Zhang J
The Oral-Gut Axis: Bidirectional Interactions Between Microbiome and Diseases.Review Journal of periodontal research | 2026-05-05
Increased colonization of typically oral microorganisms is frequently observed in the gut mucosa or lumen of individuals with gastrointestinal disorders, including patients with inflammatory bowel disease and colorectal cancer. Accumulating clinical and experimental evidence indicates that this phenomenon, known as “gut oralization,” plays an important role in the pathogenesis of these diseases. Although several physiological barriers normally restrict the translocation and ectopic colonization of microorganisms from the oral cavity to the gut, certain oral pathobionts-often enriched in individuals with oral diseases such as periodontitis-have evolved specialized strategies to overcome these defenses. This review examines the bidirectional interactions through which bacterial traits, including unique adhesion systems and metabolic adaptations, support colonization and expansion within the gastrointestinal tract, as well as how disease-associated alterations in the gut environment and increased host vulnerability facilitate ectopic colonization by bacteria of oral origin. By integrating clinical and mechanistic evidence, this review highlights the potential of targeting the oral-gut microbial axis as a therapeutic approach for preventing and treating chronic gastrointestinal disorders.
Ebihara S, Kamada N
[TNF-alpha Inhibitor-Induced Pulmonary Sarcoidosis]. Pneumologie (Stuttgart, Germany) | 2026-05-04
TNF-alpha inhibtors represent an established option for autoimmune disorders such as rheumatoid arthritis, psoriasis and chronic-inflammatory bowel diseases as well as for granulomatous diseases including sarcoidosis. Their primary mode of action is antagonistic, blocking the interaction of TNF-alpha with its receptors TNFR1 and TNFR2. Currently five TNF-alpha inhibitors are clinically used: infliximab, adalimumab, golimumab, certolizumab and etanercept.In rare cases TNF-alpha inhibitors may induce sarcoidosis through a paradoxical reaction. This phenomenon is observed most frequently during treatment with etanercept, although the underlying mechanisms remain unclear. The clinical presentation of TNF-alpha inhibitor-induced sarcoidosis closely resembles that of idiopathic sarcoidosis and is characterized by a heterogeneous, inflammatory and granulomatous disease pattern with affection of multiple organ systems. Depending on the causative active agent, a differing distribution of clinical manifestations may occur.From a diagnostic perspective, laboratory analyses and the histological confirmation of the affected organ demonstrating epithelioid cell granulomas are essential. The cornerstone of therapy is the immediate discontinuation of the triggering TNF-α inhibitor. In selected cases, adjunctive systemic corticosteroid therapy may be considered. With timely recognition and appropriate management, the prognosis is generally favourable. TNF-alpha-Inhibitoren sind etablierter Bestandteil in der Therapie autoimmuner Erkrankungen wie rheumatoider Arthritis, Psoriasis und chronisch-entzündlichen Darmerkrankungen (CED) sowie granulomatöser Erkrankungen wie der Sarkoidose. Sie wirken überwiegend als Antagonisten, indem sie die Bindung von TNF-alpha an seine Rezeptoren TNFR1 und TNFR2 hemmen. Derzeit stehen 5 TNF-alpha-Blocker zur Verfügung: Infliximab, Adalimumab, Golimumab, Certolizumab und Etanercept.In seltenen Fällen können TNF-alpha-Inhibitoren im Rahmen einer paradoxen Reaktion die Entwicklung einer Sarkoidose induzieren. Dieses Phänomen wird am häufigsten unter Etanercept beobachtet; die zugrunde liegenden Mechanismen sind bislang unklar. Klinisch ähnelt die durch TNF-alpha-Blocker induzierte Sarkoidose der idiopathischen Form und zeigt ein heterogenes, inflammatorisches und granulomatöses Krankheitsbild mit potenzieller Beteiligung verschiedener Organsysteme. Abhängig vom auslösenden Wirkstoff können sich unterschiedliche Verteilungsmuster klinischer Manifestationen zeigen.Diagnostisch ist neben laborchemischen Untersuchungen insbesondere der histologische Nachweis epitheloidzelliger Granulome im betroffenen Organ entscheidend. Therapeutisch steht die sofortige Beendigung der auslösenden TNF-alpha-Inhibitor-Therapie im Vordergrund. In einigen Fällen kann eine zusätzliche systemische Steroidtherapie erwogen werden. Bei frühzeitiger Diagnosestellung und konsequentem Handeln ist die Prognose i.d.R. günstig.
Berger M, Windisch W, Schumacher F, Ploenes N
The Overlap Between Crohn’s Disease and Intestinal Tuberculosis: A Never-Ending Story.Review Medicina (Kaunas, Lithuania) | 2026-04-21
The prevalence of Crohn’s disease has increased over the last few decades, even in developing countries, whereas that of intestinal tuberculosis has decreased, which places both diseases at an epidemiological crossroads. Crohn’s disease and intestinal tuberculosis share many clinical, endoscopic, imaging, and pathological features, which sometimes make differential diagnosis very difficult; an accurate diagnosis is, however, very important since an erroneous treatment can worsen the evolution or delay proper therapy. The association between past TB infection and Crohn’s disease can make the diagnosis especially hard. This review summarizes current data on specific features that allow differentiation between Crohn’s disease and intestinal tuberculosis, paying particular attention to the microbiome, clinical signs, endoscopy, cross-sectional imaging, bacteriological, and immunological findings detailed. The importance of computerized models and scores for the differentiation is also detailed, because common features may make the differentiation based on a single criterion difficult.
Cazacu SM, Streba CT, Constantin C, Ionele CM, Rogoveanu I, Popescu AV, Florescu MM
Biochemistry of Human Gut Microbiota: Related Diseases and Dietary Interactions.Review Molecules (Basel, Switzerland) | 2026-04-21
The human gut microbiota represents a complex and dynamic ecosystem of trillions of microorganisms that play a fundamental role in maintaining physiological homeostasis, regulating metabolism, and modulating the immune system. This narrative review explores the biochemical intricacies of the gut microbiome, focusing on the dominant phyla (Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, Verrucomicrobia, Fusobacteria) and their specific contributions to host health. A critical emphasis is placed on the metabolic outputs of these microorganisms, such as short-chain fatty acids (SCFAs) like butyrate, which serve as vital energy sources and anti-inflammatory signaling molecules. Conversely, the review examines how dysbiosis, the disruption of microbial balance, is mechanistically linked to the pathogenesis of diverse conditions, including obesity, diabetes mellitus, inflammatory bowel disease (IBD), and gout. Furthermore, it highlights the profound impact of dietary interventions on microbial architecture, notably, how non-digestible carbohydrates promote beneficial taxa and eubiosis, while high-fat and high-sugar diets drive metabolic endotoxemia and systemic inflammation. By synthesizing current knowledge on microbial biotransformations of proteins and polyphenols, this work underscores the bidirectional relationship between nutrition and the microbiome. Ultimately, understanding these biochemical interactions is essential for developing targeted probiotic, prebiotic, and nutritional strategies to prevent and manage chronic metabolic and inflammatory disorders.
Toydemir S, Merey G
The Role of Microbiota and Fecal Transplantation in Inflammatory Bowel Disease.Systematic review Pathogens (Basel, Switzerland) | 2026-04-21
Inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn’s disease (CD), are consistently associated with alterations in gut microbial communities, although the extent and characteristics of these alterations vary across studies, supporting a potential role of the microbiota in disease pathogenesis and therapeutic modulation. We conducted a systematic review to synthesize current evidence on microbiota alterations in IBD and the clinical application of fecal microbiota transplantation (FMT). A total of 118 studies were included (76 focused on microbiota profiling and 42 evaluated FMT as therapy). Across heterogeneous study designs and microbial characterization methods, reduced microbial diversity was the most consistently reported alteration, generally more pronounced in CD than in UC. Depletion of Faecalibacterium prausnitzii-a key butyrate producer with anti-inflammatory properties-was commonly reported, often accompanied by functional impairment in short-chain fatty acid production. Microbial patterns were frequently associated with mucosal inflammation and varied across disease phenotypes; these patterns have been increasingly explored as predictors of treatment response and relapse, although mechanistic interpretation remains limited and causal relationships are difficult to establish. Evidence from randomized controlled trials suggests potential efficacy of FMT in UC, particularly with intensive or repeated protocols, whereas data in CD remain limited and heterogeneous, with signals of benefit often appearing transient. FMT was generally well tolerated, but long-term safety data remain scarce. Emerging multi-omic approaches are reshaping the field by integrating taxonomic and functional insights, with potential implications for risk stratification, diagnosis, prognosis, and therapeutic optimization. Further standardized, longitudinal, and mechanistically oriented studies are required to translate microbiome research into clinically actionable strategies in IBD.
Lagos I, Pérez de Arce E, Faggiani I, D’Amico F, Zilli A, Furfaro F, Massironi S, Cicerone C, Solitano V, Parigi TL
Bacillus licheniformis Alleviates DSS-Induced Ulcerative Colitis in Mice by Repairing the Intestinal Barrier and Regulating Gut Microbiota and Its Metabolism. Nutrients | 2026-04-21
Inflammatory bowel disease (IBD) is a gut-based idiopathic disease characterized by chronic and relapsing inflammatory progression and intricate pathophysiology. It is now known that the key etiologies of IBD include immune dysregulation, imbalances in the gut microbiota, and metabolic disruptions. Probiotics are now the potential treatment for IBD, due to their ability to regulate the host immune system and microbiota of the gut. The current study analytically tested the preventive benefit of Bacillus licheniformis BL-01 on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) and also expounded on its molecular pathogenesis. Our results demonstrate that supplementation with BL-01 effectively mitigates DSS-induced weight loss, an elevated disease activity index (DAI), and colonic tissue injury in mice. Concomitantly, BL-01 rectifies dysregulated inflammatory cytokine profiles, attenuates oxidative stress, and restores the expression of colonic tight junction proteins as well as the number of goblet cells. Furthermore, BL-01 modulates the gut microbiota diversity by increasing the abundance of beneficial bacterial genera such as Duncaniella and decreasing the abundance of pathogenic genera such as Helicobacter. Notably, BL-01 restores DSS-induced microbial metabolic dysregulation, modulates key metabolic pathways including arachidonic acid metabolism and steroid hormone biosynthesis, and regulates associated metabolites to ameliorate UC. Finally, Bacillus licheniformis BL-01 mitigates oxidative stress, reverses gut dysbiosis and metabolic disorders, and has a protective effect on UC. The findings give new information on the development of probiotic-based therapeutics in the prevention and treatment of IBD.
Ma H, Xu M, Yu Y, Xia Z, Rahim MF, A M, Wang Z, Xu C, Li J
Gut microbiota-M cell co-culture in inflammatory bowel disease and its therapeutic potential in organoid platforms.Review Frontiers in pharmacology | 2026-04-20
Dysbiosis of the gut microbiota is a key driver in the onset and persistence of inflammatory bowel disease (IBD). However, the mechanisms by which microbes influence mucosal immunity via specific epithelial routes remain incompletely elucidated. Microfold (M) cells within follicle-associated epithelium serve as a critical “gateway” for luminal antigens and microbes to access the mucosal immune system. While essential for surveillance of commensal microbes, M cells could also be exploited by adherent-invasive strains and adverse environmental factors to amplify inflammation. Recent studies suggest that both in Crohn’s disease and ulcerative colitis, M cell abundance and function are aberrantly regulated, linking microbial imbalance with heterogeneous mucosal inflammatory phenotypes. Traditional animal models and two-dimensional culture systems retain limited capacity to selectively manipulate M cells without perturbing systemic immunity, thereby constraining systematic studies of microbiota-M cell co-cultures. Advances in intestinal organoid technology now enable controlled induction of functionally mature M cells within three-dimensional epithelial structures, and have started to shed light on the roles of RANKL signaling, negative regulators, and microbe-associated factors in M cell differentiation and homeostasis. In this review, we focused on key evidence supporting microbiota-M cell interactions in IBD, discussed how M cell-enriched intestinal organoid models could be leveraged to dissect the impact of pathogenic microbes, candidate probiotics, dietary components, and existing therapies on these interactions as well as to evaluate the related potential and limitations for microbiome interventions and drug screening. Integrating gut microbial plasticity with M cell epithelial entry and organoid platforms promises to provide new experimental foundations and theoretical support for individualized microbiome-based therapies and targeted mucosal treatments in IBD.
Zuo S, Kurumi H, Ogihara R, Kanda T, Isomoto H
The Structure-Decoding-Conversion-Effect Paradigm of Natural Polysaccharides for Gut Microbiota Remodeling in Ulcerative Colitis.Review Nutrients | 2026-04-20
Ulcerative colitis (UC), a chronic inflammatory bowel disease, is closely associated with disturbances in the gut microbiota. Natural polysaccharides, owing to their unique “indigestibility” and prebiotic properties, represent a potential strategy for intervening in UC by remodeling the gut microecology. This review summarizes the mechanisms by which natural polysaccharides alleviate UC through modulation of the gut microbiota, with a particular focus on the structure-activity relationship between the structural features of natural polysaccharides and their microbiota-regulating functions. Analytical studies indicate that polysaccharides with distinct structures can be recognized and degraded by specific carbohydrate-active enzymes (CAZymes) in the gut microorganisms, leading to the targeted enrichment of beneficial genera such as Roseburia, Lactobacillus, and Akkermansia, while simultaneously suppressing pro-inflammatory genera such as Escherichia-Shigella and Helicobacter. This structure-dependent microbial remodeling ultimately enhances the production of key metabolites and exerts comprehensive therapeutic effects, including repair of the intestinal barrier, suppression of excessive inflammation, and alleviation of oxidative stress, via activation of signaling pathways such as AMP-activated protein kinase (AMPK) and nuclear factor erythroid 2-related factor 2 (Nrf2) and inhibition of pathways such as nuclear factor kappa-B (NF-κB). By exploring the paradigm of “Structure-Decoding-Conversion-Effect” based on precise microecological regulation of polysaccharide structures, this paper provides a crucial theoretical foundation and design strategy for developing targeted microecological interventions.
Rong XQ, Zhang XM, Yan L, Tan Y, Lu C
Therapeutics & Mechanisms (18 papers)
Comparative Effectiveness and Safety of Tofacitinib, Filgotinib, and Upadacitinib in Ulcerative Colitis: A Multicenter Real-World Cohort Study. Advances in therapy | 2026-05-09
Tofacitinib, filgotinib, and upadacitinib are Janus kinase inhibitors (JAKis) available for ulcerative colitis (UC) refractory or intolerant to at least one advanced therapy; their comparative effectiveness in clinical practice remains uncertain. We conducted a multicenter retrospective study including adult UC patients initiating tofacitinib, filgotinib, or upadacitinib (September 2020-June 2025). Clinical remission (partial Mayo score ≤ 1), steroid-free clinical remission, biochemical remission, and endoscopic remission (Mayo endoscopic score = 0) were assessed at predefined time-points. Baseline differences were controlled using inverse probability of treatment weighting (IPTW), and time-to-event and longitudinal analyses were performed. After IPTW, the pseudo-population included 627 patients (tofacitinib = 179, filgotinib = 138, upadacitinib = 310). In the weighted cohort, clinical remission probabilities at weeks 8, 24, and 52 were 17.5%, 40.7%, and 61.3% with upadacitinib, 11.8%, 33.8%, and 54.6% with tofacitinib, and 6.7%, 29.0%, and 52.0% with filgotinib, respectively; p < 0.001 at weeks 8 and 24; p = 0.040 at week 52. Steroid-free clinical remission showed a similar gradient (14.2%, 39.2%, and 59.8% with upadacitinib; 9.2%, 31.2%, and 50.8% with tofacitinib; 4.4%, 27.6%, and 49.8% with filgotinib, respectively; all p < 0.001. Biochemical remission was also achieved more frequently with upadacitinib at weeks 8 and 16, although differences between treatments were no longer significant during maintenance. At week 52, endoscopic remission was 18.8% with tofacitinib, 36.6% with upadacitinib, and 19.5% with filgotinib (p = 0.039). Overall adverse events, particularly infections and herpes zoster, were more frequent with tofacitinib, whereas filgotinib had fewer non-serious events; serious adverse events and colectomy risk were uncommon and similar across groups. All three JAKis were effective, but upadacitinib yielded the highest remission rates, while tofacitinib and filgotinib differed mainly in safety, supporting individualized drug positioning according to efficacy needs and patient-specific risks.
Tursi A, Pasta A, Elisei W, Barberio B, Mocci G, Savarino EV, de Barba C, Maconi G, Cataletti G, Scaldaferri F
EFFECTIVENESS OF RISANKIZUMAB AFTER USTEKINUMAB FAILURE IN CROHN’S DISEASE: A MULTICENTER RETROSPECTIVE COHORT STUDY.★ Gastroenterology | 2026-05-08
Abstract not available.
Mehta-Dhand S, Hamidi N, Clarke AN, Hoentjen F, Panaccione R, Ma C
Safety of Janus kinase inhibitors compared to biologic therapy in patients with inflammatory bowel disease. Intestinal research | 2026-05-07
There is a paucity of data regarding the comparative safety of Janus kinase inhibitors (JAKi) compared to biologic therapy in inflammatory bowel disease (IBD). A retrospective cohort study was conducted using the U.S. Collaborative Network to assess the risk of adverse events in patients with IBD on JAKi compared to biologic therapies (tumor necrosis factor inhibitor, ustekinumab or vedolizumab). Outcomes assessed included infections, major adverse cardiovascular events (MACE), malignancy, venous thromboembolism (VTE), gastrointestinal perforations and laboratory abnormalities within 2 years. 1:1 propensity score matching (PSM) was performed. There were 3,186 patients in the JAKi cohort (mean age 44.3 ± 17.1, 46.5% male sex, 85.7% ulcerative colitis, 72% tofacitinib) and 60,462 patients in the biologic cohort. After PSM, there was no difference in the risk of bacterial (adjusted odds ratio [aOR], 1.08; 95% confidence interval [CI], 0.82-1.43), viral (aOR, 1.06; 95% CI, 0.84-1.32), or fungal infections (aOR, 1.10; 95% CI, 0.84-1.44), MACE (aOR, 0.72; 95% CI, 0.47-1.10), malignancy (aOR, 0.98; 95% CI, 0.71-1.35), and VTE (aOR, 0.95; 95% CI, 0.67-1.34). This was consistent in subgroup analyses based on IBD type, JAKi type and age group. There was a higher risk of low-density lipoprotein ≥ 190 mg/dL (aOR, 1.78; 95% CI, 1.03-3.05) and grade 3 or higher lymphopenia (aOR, 2.28; 95% CI, 1.60-3.26) in the JAKi cohort. There was no difference in the 4-year risk of MACE or malignancy in the tofacitinib cohort compared with the biologic cohort. Our real-world study did not show an increased risk of adverse events except severely elevated LDL and lymphopenia in patients on JAKi compared to biologic therapy.
Kochhar GS, Khataniar H, Dulai PS, Desai A
Multivariable genome-wide analysis elucidates the shared genetic architecture, immunosenescence features, and gut-origin therapeutic targets of ulcerative colitis-associated multisystem inflammation. Inflammation research : official journal of the European Histamine Research Society … [et al.] | 2026-05-07
Over 25% of patients with ulcerative colitis (UC) develop extraintestinal manifestations (EIMs), resulting in significant systemic morbidity. We define the shared genetic foundation of these manifestations as the UC-associated Multisystem Inflammatory Genetic Architecture (UC-MIGA). This study aims to identify shared genomic drivers and actionable immunosenescence therapeutic targets across the UC-EIM spectrum. We applied genomic structural equation modeling (SEM) to seven European-ancestry GWAS datasets (UC, deep vein thrombosis, ankylosing spondylitis, primary sclerosing cholangitis, pyoderma gangrenosum, interstitial lung disease, and erythema nodosum) to identify a shared latent genetic factor (F1). Post-SEM analyses included FUMA mapping, SuSIE/FINEMAP fine-mapping, FUSION/FOCUS transcriptome-wide studies, MAGMA enrichment, CELLECT deconvolution, LDSC partitioned heritability, and single-cell eQTL Mendelian randomization (MR). UC exhibited the highest standardized factor loading (0.9801) on F1, justifying its use as a representative proxy for UC-MIGA in downstream analyses. UC-telomere relationships were assessed via tissue-specific eQTL/sQTL enrichment across 49 GTEx tissues, spatial transcriptomics (gsMap), single-cell profiling (GSE214695, GSE163974), hdWGCNA, and colocalization analyses (eCAVIAR, fastENLOC). SEM identified substantial genetic overlap (CFI = 1.0, SRMR = 0.17). Within the UC-MIGA framework, we identified 17,005 SNPs (P ≤ 1 × 10⁻2⁰⁰), 2,622 risk loci, and 152 high-confidence effector genes. Pathways implicated Th17/Treg imbalance and inflammasome signaling. Super-enhancer regions showed exceptional heritability enrichment (80.16%, fold = 4.79, p = 0.0007). MR identified 35 causal immune cell-gene associations. UC-telomere analyses revealed convergence in colon-specific DNA repair-mitochondrial energetics-telomere maintenance pathways, with B cells prioritized as the core cell type. Colocalization identified NKX2-3 and LINC01475 as high-confidence shared candidates. Embryonic intestinal enrichment supported the developmental origins of this systemic axis. UC-MIGA represents a genetically coherent architecture driven by super-enhancer-mediated epigenetic dysregulation, Th17/Treg imbalance, and immunosenescence features, including telomere dysfunction and B-cell exhaustion. The ‘developmental vulnerability-environmental trigger’ model explains the gut-origin inflammatory cascade underlying extraintestinal manifestations, with UC-telomere analysis providing a genomic foundation for systemic therapeutic strategies targeting the inflammation-aging nexus.
Tang S, Yao X, Wang S, Zhu F, Zeng W, Lai D, Meng X, Zhang X, Zhu Z, Zhang T
Immune cell-targeted nanocarrier delivery systems for inflammatory bowel disease therapy: mechanisms and strategies.Review International journal of pharmaceutics | 2026-05-07
Inflammatory bowel disease (IBD) is a chronic intestinal disorder caused by immune dysregulation, leading to persistent inflammation and recruiting a large number of immune cells to the intestinal inflammation sites. When immune cells become aberrantly activated, macrophages, neutrophils, dendritic cells, T cells and B cells infiltrate affected intestinal sites, releasing pro-inflammatory cytokines that amplify tissue damage and perpetuate disease progression. Base on pathological mechanisms, immune cell-targeted nanocarrier systems have emerged as innovative platforms for precise drug delivery to inflamed colonic regions, minimizing off-target effects, regulating immune imbalance and enhancing therapeutic efficacy. This review systematically examines the roles of key immune cells and their associated signaling pathways in IBD pathogenesis, with a particular focus on immune regulatory mechanisms at inflammatory foci. Furthermore, it explores design strategies for nanoparticles functionalized with specific ligands, including mannose, folic acid, lactoferrin, and hyaluronic acid, which facilitate selective targeting of immune cells. These modifications optimize immune cell phenotype modulation, cytokine secretion control, and tissue repair, significantly reducing systemic toxicity and improving drug bioavailability. Finally, challenges and future perspectives, including ligand specificity optimization, clinical translation barriers, and multifunctional nanoparticle development, are discussed to advance IBD treatment paradigms. Collectively, this comprehensive summary of immune cell-targeted nanotherapeutics provides novel insights into precision treatment strategies for IBD, paving the way for more effective and targeted therapeutic interventions.
Tang Y, Wu Z, Zhao H, Liang W, Qu A, Wang R, Gao S, Zhao P, Liu J, Zhang Z
Advanced combination therapy: Janus kinase inhibitors and TNF inhibitors in the treatment of patients with inflammatory bowel disease.Case report Revista de gastroenterologia de Mexico (English) | 2026-05-06
Abstract not available.
Carvajal F, Núñez P, Quera R, Pizarro G, Flores L
Hepatitis B virus infection or reactivation and HBV-related liver dysfunction in patients with inflammatory bowel disease receiving infliximab: a nationwide real-world study. MedScience | 2026-05-06
Infliximab (IFX) for inflammatory bowel disease (IBD) treatment may increase the risk of hepatitis B virus (HBV) reactivation, particularly in areas with high HBV prevalence such as China. This study aimed to evaluate HBV reactivation/infection, liver dysfunction, vaccination efficacy and strategies in IBD patients undergoing IFX therapy. This retrospective, multicenter study included 4183 IBD patients from 15 hospitals across China, who were divided into six groups according to the HBV status. Demographic features, HBV vaccination status, reactivation/infection rates, and liver dysfunction outcomes were collected, with data collection performed from 2009 to 2022. We found that HBV reactivation rate was notably higher in HBsAg positive group than other groups (P < 0.05) despite antiviral treatment. Although only 29% of patients were immunized at IFX initiation and almost no patients got vaccinated against HBV during IFX treatment, no patients experienced HBV infection in the susceptible population group. The study underscores a critical need for rigorous HBV screening before IFX initiation. Despite antiviral prophylaxis, the importance of continuous monitoring of HBV DNA is necessary for HBsAg positive patients. HBsAg negative patients, including the susceptible population, had a very low risk of new HBV infection, thus reassuring patients and physicians of the safety of IFX in this cohort.
Liu R, Wu T, Tang J, Zhang H, Fan Y, Sun H, Xie C, Zhou Q, Xu H, Zhu Y
Effectiveness and safety of mirikizumab in ulcerative colitis: real-world data from the Latium Net.Multicenter study BMJ open gastroenterology | 2026-05-05
To evaluate the effectiveness and safety of mirikizumab in patients with ulcerative colitis in clinical practice. We conducted a retrospective, multicenter cohort study across five Italian inflammatory bowel disease centers. Patients initiating mirikizumab between November 2024 and May 2025 were included. The primary endpoint was steroid-free clinical remission (SFCR) at 12 weeks, defined as the absence of rectal bleeding and near-normal stool frequency without corticosteroids. Secondary outcomes included clinical response (≥30% improvement in stool frequency and rectal bleeding), biochemical response (normalisation of fecal calprotectin (FCP) and C-reactive protein (CRP)), and safety (any adverse events). Follow-up at 24 weeks was assessed when available. Subgroup analyses were performed according to prior exposure to biologics (including ustekinumab) and induction regimen. A total of 95 patients were included (mean age 49.9±16.9 years; 50.5% male); 12.6% were biologic naïve and 17 (17.9%) received extended induction. At week 12, 43.2% of patients (41/95) achieved SFCR, 61.1% (58/95) clinical response, and 32/95 (33.7%) biochemical remission. SFCR rates were similar between biologic-naïve and biologic-experienced patients (42.6% vs 43.8%, p=0.906). SFCR rates were 36.2% and 88.2% in patients receiving extended and standard induction, respectively (p=0.002). At week 24, prior ustekinumab exposure was associated with numerically lower SFCR, although this difference was not statistically significant (38.5% vs 73.7%; OR=0.22, 95% CI 0.05 to 1.01, p=0.052). Changes in biomarkers were not statistically significant at week 12 (CRP Δ-0.08 mg/dL, p=0.464; FCP Δ-249 µg/g, p=0.127). Three patients discontinued treatment due to lack of efficacy. No adverse events were observed. Mirikizumab demonstrated meaningful clinical effectiveness and a favourable safety profile in a real-world setting, including in biologic-experienced patients.
Murgiano M, Balestrieri P, Calabrese E, Fiorino G, Festa S, Pugliese D, Di Vincenzo F, Puca P, Parello S, Vespasiano V
Improvement in Health-Related Quality of Life in Patients With Moderate to Severe Crohn’s Disease Treated With Risankizumab Versus Ustekinumab in the Phase 3B SEQUENCE Study.★ The American journal of gastroenterology | 2026-05-05
Normalized quality of life represents a crucial long-term treatment goal in Crohn’s disease (CD). We evaluated the effect of risankizumab (RZB) versus ustekinumab (UST) on achieving clinically meaningful improvements in patient-reported outcomes (PROs) in the phase 3b head-to-head SEQUENCE study. Adults with moderate-to-severe CD who have failed prior anti-tumor necrosis factor therapy were randomized 1:1 to recommended induction and maintenance doses of RZB or UST. The proportion of patients who achieved Inflammatory Bowel Disease Questionnaire (IBDQ) response, IBDQ remission, and improvements in 36-item Short-Form Health Survey (SF-36v2) physical and mental component summary (PCS and MCS, respectively) scores was evaluated at weeks 24 and 48. The proportion of patients experiencing improvement in select symptoms of the IBDQ was reported. Analysis included 520 patients (RZB: N=255; UST: N=265). At week 24, greater proportions (all P≤.01) of RZB- versus UST-treated patients achieved IBDQ response (75.3% vs 64.2%), IBDQ remission (52.5% vs 30.9%), and improvements in SF-36v2 PCS (65.9% vs 53.2%). At 24 weeks, lower proportions (all P≤.05) of RZB- versus UST-treated patients experienced fatigue (51.4% vs 69.1%), difficulty sleeping (37.7% vs 54.3%), depression (34.1% vs 42.6%), anxiety (34.1% vs 49.8%), and bowel urgency (27.1% vs 40.0%) “all of the time to some of the time.” Improvements were sustained through week 48. RZB was more effective than UST in achieving sustained clinically meaningful PRO improvements including IBDQ response and remission, and in reducing frequency of select symptoms of the IBDQ through week 48 among patients with moderate-to-severe CD.
Loftus EV, Joshi N, Sands BE, Jairath V, Blumenstein I, Shukla N, Kligys K, Anschutz T, Griffith J, Zambrano J
Multi-modal therapeutic approaches to inflammatory bowel disease: plant-derived compounds, nanoparticle drug delivery systems, and gene-based interventions.Review Molecular biology reports | 2026-05-05
Inflammatory bowel disease (IBD) is a chronic, relapsing inflammatory disorder primarily affecting the gastrointestinal tract. The pathogenesis arises from complex interactions among genetic predisposition, immune dysregulation, and gut microbiota alterations. Recent advances in molecular biology, genomics, and microbiome research have identified novel therapeutic targets, enabling the development of innovative treatment strategies. Natural products derived from plants offer bioactive compounds with anti-inflammatory, antioxidant, and immunomodulatory properties, gaining attention for IBD symptom management. Conventional therapeutic management includes aminosalicylates, immunomodulators, corticosteroids, and biologics; however, 30-50% of patients show inadequate response, and oral drug delivery faces challenges due to gastrointestinal environmental heterogeneity. Recent years have witnessed substantial advances in nanoparticle-based drug delivery systems for IBD, offering improved targeting capabilities, enhanced therapeutic efficacy, and better tolerability through stimuli-responsive platforms (ROS-sensitive, pH-responsive) and active targeting strategies. Nanoparticle-mediated gene therapy, including siRNA, miRNA, and emerging CRISPR-based approaches, represents a paradigm-shifting strategy for modulating aberrant gene expression in IBD. This comprehensive review synthesizes the current understanding of IBD pathophysiology, evaluates both conventional and emerging therapeutic approaches, and provides critical analysis of advanced nanoparticle delivery systems and gene-based therapeutic strategies.
Komal A, Ilyas D, Khan MU, Rehman MKU, Hassan T, Ayub H, Naqi N, Ullah N, Ilyas U
Silk fibroin and oxidized glycyrrhizic acid hydrogel loaded with mesalazine nanoparticles: A promising strategy for ulcerative colitis treatment. Biomaterials advances | 2026-05-01
Ulcerative colitis (UC) is a chronic inflammatory bowel disease with rising global incidence, imposing a significant burden on healthcare systems. Current treatments, including aminosalicylic acid derivatives like mesalazine, often face limitations such as low water-solubility and bioavailability. This study explores the development of a silk fibroin (SF)/oxidized glycyrrhizic acid (OG)/silk sericin-mesalazine (SM) hydrogel for rectal administration to enhance therapeutic efficacy. The SF/OG/SM hydrogel exhibits excellent adhesion, injectability, and gradual release of SM nanoparticles. It demonstrates high biocompatibility with negligible cytotoxicity and hemolysis, along with potent antioxidant and anti-inflammatory activities. In vivo studies reveal significant alleviation of UC symptoms, including reduced disease activity index (DAI), preserved colon length, and improved histological outcomes. The hydrogel suppresses the abundance of Escherichia coli and Enterococcus, while promoting the proliferation of Bifidobacterium and Lactobacillus, as well as the expression of tight junction proteins. Overall, the SF/OG/SM hydrogel presents a promising therapy for UC with enhanced therapeutic potential.
Zhang J, Xiao T, Wu X, Lin Y
Effect of Mirikizumab on Clinical and Endoscopic Outcomes Based on Prior Advanced Therapy Failure in Patients With Moderately to Severely Active Ulcerative Colitis.RCT★ United European gastroenterology journal | 2026-05
Mirikizumab demonstrated efficacy in moderately-to-severely active ulcerative colitis, including in patients with prior advanced therapy failure (PATF) (Phase 3: LUCENT-1 [NCT03518086], LUCENT-2 [NCT03524092]). This post hoc analysis evaluates mirikizumab efficacy by number/mechanism of PATF. LUCENT-1 patients received 300 mg mirikizumab or placebo; mirikizumab induction responders entered LUCENT-2 and received 200 mg mirikizumab or placebo until week (W)52. Mirikizumab induction non-responders received extended induction with open-label 300 mg mirikizumab between W12 and W24. Extended induction responders received open-label 200 mg mirikizumab between W24 and W52. In each population, efficacy was analyzed by subgroups based on PATF number (0, 1, ≥ 2 [2-3]) and mechanism (including difficult-to-treat [DTT]: anti-TNF plus tofacitinib and/or vedolizumab). At baseline, 479/1162 patients (41.2%) had (≥ 1) PATF, of which 177 (37.0%) had DTT. Among mirikizumab-treated patients (n = 868), W12 clinical response was achieved by 69.8%, 63.9%, 45.3%, and 41.9% of the 0-PATF, 1-PATF, ≥ 2-PATF, and DTT subgroups, respectively. 42.1% (365/868) continued with maintenance treatment. Among W12 responders, 51.9% (0-PATF), 44.2% (1-PATF), 49.0% (≥ 2-PATF), and 42.9% (DTT) achieved clinical remission at W52. Over half of the patients (54.0% [147/272]) in the extended induction population had PATF; 51.0% (75/147) were DTT. At W24, clinical response was achieved by 62.4%, 41.4%, 49.5%, and 49.3% of the 0-PATF, 1-PATF, ≥ 2-PATF, and DTT subgroups. Of this 49.3% of the DTT subgroup (extended induction responders), 38.9% (14/36) achieved W52 clinical remission. Mirikizumab induction and maintenance is efficacious in moderately-to-severely active ulcerative colitis with or without prior failure of advanced therapy, including difficult-to-treat disease. LUCENT-1: NCT03518086; LUCENT-2: NCT03524092.
Hart A, Navabi S, D’Haens G, Matsuoka K, Martín-Arranz MD, Atreya R, Samaan KH, Dhesi E, Redondo I, Zhu B
[Relationships of interleukin-7 receptor gene polymorphisms with the risk of Crohn’s disease and the efficacy of infliximab]. Zhonghua yi xue za zhi | 2026-05
Objectives: To explore the relationships of interleukin-7 receptor (IL-7R) gene polymorphisms with the risk of Crohn’s disease (CD), as well as the efficacy of infliximab (IFX) in patients with CD. Methods: The CD patients (CD group) and healthy controls (control group) at the Second Affiliated Hospital of Wenzhou Medical University between January 2020 and May 2025 were retrospectively collected. Genotypes of IL-7R gene at loci rs6897932, rs1494555, rs1494558 were examined in both groups. According to Montreal CD Classification, the disease locations were divided into terminal ileal-type, colonic-type, ileocolic-type and upper gastrointestinal-type. Among CD patients receiving IFX treatment, the clinical response was evaluated by Crohn’s Disease Activity Index (CDAI) at week 14 of follow-up. The patients were divided into the clinical response group (a decline of CDAI≥100 points compared with week 0) and the clinical non-response group. The efficacy of endoscopy was assessed by Simplified Endoscopic Score for Crohn’s Disease (SES-CD) at week 32. The patients were divided into the mucosal healing group (SES-CD≤2 points or absence of mucosal ulcerations) and the mucosal non-healing group. The distribution differences of IL-7R gene polymorphisms were compared between CD group and control group, among CD patients with different clinical phenotypes, between the clinical response group and the clinical non-response group, as well as between the mucosal healing group and the mucosal non-healing group. The genotypes or alleles with distribution differences were included into multivariate logistic regression model to investigate the relationships of IL-7R gene polymorphisms with the risk of CD, the clinical phenotypes, and the clinical efficacy of IFX in CD patients. Results: The CD group consisted of 303 participants [200 males and 103 females, aged 30 (23, 40) years]. The control group consisted of 514 participants [313 males and 201 females, aged 32 (26, 42) years]. The variant allele (T) [14.0% (85/606) vs 18.5% (190/1 028)] of locus rs6897932 were less frequent in the CD group than that in the control group, but the difference was not statistically significant after adjustment (adjusted P=0.054). The homozygous variant genotype (TT) of locus rs6897932 in the patients with terminal ileal-type and ileocolic-type CD group were less frequent than that with colonic-type CD [0.8% (2/261) vs 9.5% (4/42), adjusted P=0.009]. The homozygous variant genotype (TT) of locus rs6897932 (OR=0.06, 95%CI: 0.01-0.38) was the related factor influencing the terminal ileum involvement (the disease location is terminal ileal-type or ileocolic-type) in CD patients. A total of 112 CD patients were treated with IFX. There were 78 cases in the clinical response group and 34 cases in the clinical non-response group at week 14 of IFX treatment. The variant genotype (CT+TT) [38.5% (30/78) vs 11.8% (4/34), adjusted P=0.015] and variant allele (T) [20.5% (32/156) vs 5.9% (4/68), adjusted P=0.018] of locus rs6897932 in the clinical response group were more frequent than those in the clinical non-response group. The variant genotype (CT+TT) (OR=5.17, 95%CI: 1.54-17.36) of locus rs6897932 was the related factor influencing the clinical response at week 14. There were 43 cases in the mucosal healing group and 69 cases in the mucosal non-healing group at week 32 of IFX treatment. The variant genotype (TC+CC) [65.1% (28/43) vs 85.5% (59/69), adjusted P=0.036] of locus rs1494558 in the mucosal healing group was less frequent than that in the mucosal non-healing group. The variant genotype (TC+CC) (OR=0.24, 95%CI: 0.09-0.71) of locus rs1494558 was the related factor influencing the mucosal healing at week 32. Conclusions: The homozygous variant genotype (TT) of locus rs6897932 in IL-7R gene may be related with a lower risk of terminal ileum involvement (the disease location is terminal ileal-type or ileocolic-type). In CD patients receiving IFX treatment, the variant genotype (CT+TT) of locus rs6897932 in IL-7R gene may be related with an increased clinical response rate at week 14, while the variant genotype (TC+CC) of locus rs1494558 may be related with a reduced mucosal healing rate at week 32. 目的： 探讨白细胞介素7受体（IL-7R）基因多态性与克罗恩病（CD）发病风险及英夫利西单抗（IFX）治疗CD患者疗效的相关性。 方法： 回顾性收集2020年1月至2025年5月温州医科大学附属第二医院确诊的CD患者（CD组）和同期健康体检者（对照组）。检测两组IL-7R基因rs6897932、rs1494555和rs1494558位点的基因型。采用蒙特利尔CD分类标准，将疾病部位分为末段回肠型、结肠型、回结肠型和上消化道型。在接受IFX治疗的CD患者中，随访至第14周时采用克罗恩病活动指数（CDAI）评估临床应答情况，分为临床应答组（CDAI较第0周下降≥100分）和临床无应答组；第32周时采用简化克罗恩病内镜评分（SES-CD）评估内镜疗效，分为黏膜愈合组（SES-CD≤2分，或无溃疡）和黏膜未愈合组。比较CD组与对照组、不同临床表型CD患者组、临床应答组和临床无应答组、黏膜愈合组和黏膜未愈合组间IL-7R基因多态性的分布差异；将存在分布差异的基因型或等位基因分别纳入多因素logistic回归模型，分析IL-7R基因多态性与CD发病风险、临床表型及IFX治疗CD患者疗效的相关性。 结果： CD组303例，男200例，女103例，年龄30（23，40）岁；对照组514名，男313名，女201名，年龄32（26，42）岁。CD组rs6897932位点的变异等位基因（T）频率低于对照组［14.0%（85/606）比18.5%（190/1 028）］，但校正后差异无统计学意义（校正P=0.054）。末段回肠型+回结肠型CD患者rs6897932位点的纯合子变异基因型（TT）频率低于结肠型CD患者［0.8%（2/261）比9.5%（4/42），校正P=0.009］；rs6897932位点的纯合子变异基因型（TT）（OR=0.06，95%CI：0.010.38）是CD患者末段回肠受累（疾病部位为末段回肠型或回结肠型）的相关因素。接受IFX治疗的CD患者共112例，IFX治疗第14周时，临床应答组共78例，临床无应答组34例。临床应答组rs6897932位点的变异基因型（CT+TT）频率［38.5%（30/78）比11.8%（4/34），校正P=0.015］和变异等位基因（T）频率［20.5%（32/156）比5.9%（4/68），校正P=0.018］均高于临床无应答组；rs6897932位点的变异基因型（CT+TT）（OR=5.17，95%CI：1.5417.36）是第14周临床应答的相关因素。IFX治疗第32周时，黏膜愈合组43例，黏膜未愈合组69例。黏膜愈合组rs1494558位点的变异基因型（TC+CC）频率低于黏膜未愈合组［65.1%（28/43）比85.5%（59/69），校正P=0.036］；rs1494558位点的变异基因型（TC+CC）（OR=0.24，95%CI：0.09~0.71）是第32周黏膜愈合的相关因素。 结论： IL-7R基因rs6897932位点的纯合子变异基因型（TT）可能与CD患者末段回肠受累（疾病部位为末段回肠型或回结肠型）的风险降低相关。在接受IFX治疗的CD患者中，IL-7R基因rs6897932位点的变异基因型（CT+TT）可能与第14周临床应答率增高相关，rs1494558位点的变异基因型（TC+CC）却可能与第32周黏膜愈合率降低相关。.
Dai CX, Xu JY, Chen WW, Xu Y, Ma GL, Jiang Y
DOI: 10.3760/cma.j.cn112137-20251111-02949 | View on PubMed →
Treatment outcomes of prolonged induction or re-escalation dosing of upadacitinib in patients with inflammatory bowel disease.Letter Crohn’s & colitis 360 | 2026-04-29
Proposed treatment algorithms favor the use of upadacitinib in medically refractory Crohn’s disease (CD) and ulcerative colitis (UC). There has not yet been data published regarding efficacy of prolonged induction in CD or the efficacy of re-escalation to induction dosing in patients with either CD or UC. The aim of this study was to evaluate the real-world efficacy and safety of prolonged and/or re-escalation upadacitinib therapy in patients with inflammatory bowel disease (IBD) and prior inadequate response to standard upadacitinib treatment. This was a retrospective, dual-center study of the efficacy of prolonged induction or re-escalation of upadacitinib in patients with IBD with prior inadequate response to standard upadacitinib treatment. Fifty-five patients met eligibility criteria. Thirty-nine (70.9%) persisted on upadacitinib therapy while 16 (29.1%) met the primary endpoint for upadacitinib failure. Of those that had comparative objective data, 62.5% had improvement in endoscopic activity, 100% had normalization of an elevated CRP, and 83.3% experienced a decrease in FCP by >50%. There were no new safety signals. Over two-thirds of patients met the primary endpoint of persistence on therapy without requiring surgery, steroids, or additional biologic/small molecule inhibitor during follow-up. In a subset of patients who had adequate baseline and follow up objective data, the majority of patients had improvement in mucosal healing, decrease by 50% in FCP, and normalization of CRP. This study shows promising results that prolonged upadacitinib induction or dose re-escalation may improve clinical outcomes in a medically refractory patient population.
Axenfeld E, Chaudhary V, Clinton JW, Frohlinger M, George L, Cross RK, Axelrad JE
Exploration of novel costunolide derivatives bearing indole/indoline as anti-ulcerative colitis agents by targeting JAK2-STAT3 pathways. Bioorganic chemistry | 2026-04-27
Ulcerative colitis (UC) is a kind of hard to cure chronic inflammatory disease. In present work, a series of new costunolide derivatives bearing indole/indoline have been prepared, and anti-inflammatory activities and mechanism have been tested. The results indicated that costunolide derivatives displayed good inhibition of NO generation. The in vivo studies showed that 4c exerted good protective effects in DSS-induced UC mice model by inhibiting the expression of IL-17 A and IL-17F, reducing the infiltration of immune cells, and inhibiting the phosphorylation of JAK2-STAT3 tyrosine residues. Therefore, new costunolide derivatives could be considered as potential JAK2/STAT3 pathway modulator for treatment of UC.
Yang H, Jiang Y, Yang R, Huang Z, Mao Z, Li Y
Neutrophil count and platelet-lymphocyte ratio as simple predictors of ustekinumab response in patients with Crohn’s disease: a retrospective multicenter study.Multicenter study Frontiers in immunology | 2026-04-22
Although ustekinumab (UST) has been recommended by guidelines as a parallel first-line biologic agent for Crohn’s disease (CD), its efficacy varies among individuals. This study aimed to identify baseline clinical features and laboratory indicators that can predict clinical remission with UST to assist clinical decision-making. This retrospective study collected data from patients with CD who received UST induction and maintenance therapy across multiple centers. The primary endpoint was the rate of clinical remission at week 48. Independent predictors of clinical remission were identified by multivariate logistic regression analysis. Receiver operating characteristic (ROC) curves and the Youden index were used to determine optimal cutoff values. Among the 157 included patients, clinical and endoscopic remission rates were 76.4% (120/157) and 51.6% (81/157), respectively. Multivariate analysis showed that baseline neutrophil count and baseline platelet-lymphocyte ratio (PLR) were independent predictors of clinical remission at week 48 with UST treatment. Area under the ROC curve values for baseline neutrophil count, baseline PLR, and their combination were 0.633, 0.709, and 0.769, respectively. Optimal cutoff values for baseline neutrophil count and baseline PLR were ≤4.135×109/L and <237.912, respectively. Baseline neutrophil count and baseline PLR together constitute a simple and effective predictive model. This model may help identify patients who are more responsive to UST before treatment, offering a practical tool for individualized and precise treatment of CD.
Li L, Lin P, Xu X, Qian N, Li S, Xu M, Deng M, Sun X, Zhang Y, Xie L
A single-center clinical study on the combination of Five-flavor sophora flavescens enteric-coated capsules and vedolizumab in induction therapy for ulcerative colitis. Frontiers in immunology | 2026-04-22
The aim of this study was to evaluate the efficacy and safety of Vedolizumab (VDZ) combined with Five-flavor sophora flavescens enteric-coated capsules (FSEC) for induction therapy in Ulcerative colitis (UC). UC patients treated with FSEC and/or VDZ were enrolled and divided into combination group (VDZ+FSEC) and single drug group (VDZ). The primary end points were clinical and endoscopic response and remission rates at week 14 and week 52. Secondary end points were the 14-week corticosteroid withdrawal rate, the number of bowel movements, the number of bloody stools, improvement in inflammatory markers, and safety. The clinical response rate (97.4% vs. 79.1%, P = 0.011, 95% confidence interval(CI) 4.1%, 32.8%) and endoscopic response rate (74.4% vs. 51.2%, P = 0.031, 95%CI 2.2%, 41.4%) at week 14 in the combination group were significantly higher than those in the single-agent group. PP analysis showed that the endoscopic response rate at week 52 in the combination group was significantly better than that in the monotherapy group (85.7% vs. 62.5%, P = 0.042, 95%CI 2.0%, 44.4%), but there was no significant difference in ITT analysis. At week 14, the number of bowel movements and hematochezia scores were significantly improved in the combination group and the monotherapy group, and the improvement in the combination group was more significant at early stage and multiple time points. There were no serious adverse reactions in the two groups. FSEC combined with VDZ demonstrated superior clinical response rates and endoscopic response rates, and had greater advantages in early improvement of hematochezia and defecation frequency, compared to VDZ monotherapy, with a favorable safety profile.
Li X, Zhou L, Tian F, Li H, Xie Y
Recall urticaria caused by vedolizumab: case report and literature review.Case report Frontiers in allergy | 2026-04-21
Recall urticaria is a rare hypersensitivity phenomenon characterized by the reappearance of urticarial wheals strictly confined to previously exposed skin sites following systemic re-exposure to a trigger. Although reported with several drugs, its clinical features and underlying mechanisms remain poorly defined. A 25-year-old man with ulcerative colitis developed acute pruritic wheals localized exclusively to prior subcutaneous injection sites approximately 15 min after intravenous administration of vedolizumab. He had experienced repeated localized injection-site reactions during prior subcutaneous therapy. Histopathology revealed mild perivascular inflammation with eosinophils. The eruption resolved spontaneously within 24 h without systemic symptoms, and vedolizumab therapy was continued. This case represents the first report of vedolizumab-associated recall urticaria. A review of previously reported cases highlights strict site specificity as the defining feature, irrespective of the route or timing of re-exposure. Recall urticaria should be recognized as a site-specific hypersensitivity reaction distinct from systemic drug allergy.
Kozuma M, Hara R, Sakuragi Y, Saito-Sasaki N, Sawada Y
Biomarkers & Precision Medicine (15 papers)
Integrated Serum Pharmacochemistry, Metabolomics, and Network Pharmacology Uncover Potential Active Components and Mechanisms of Shenling Baizhu Powder in Treating Ulcerative Colitis With Spleen Deficiency and Dampness Stagnation. Biomedical chromatography : BMC | 2026-06
This study combined serum pharmacochemistry, metabolomics, and network pharmacology to uncover potential active components and mechanisms of Shenling Baizhu Powder (SLBZP) in treating ulcerative colitis with spleen deficiency and dampness stagnation (UC-SDDS), providing scientific evidence for its efficacy. Pharmacodynamic investigations demonstrated that SLBZP exhibits substantial anti-inflammatory properties and confers protection to the intestinal barrier in UC-SDDS rat models. Further, 16 active components and six core targets (BCL2, NFKB1, TNF, IL6, AKT1, CASP3) were obtained using serum pharmacochemistry and network pharmacology. Twenty-six differential metabolites in serum and 25 differential metabolites in urine were identified using untargeted metabolomics analyses. Subsequently, nine active components (butein, calycosin-7-o-β-d-glucoside, glabridin, isochlorogenic acid B, naringenin chalcone, naringenin, neoliquiritin, oroxyloside, and vanillic acid) were identified from SLBZP for treating UC-SDDS by integrating network pharmacology and chinmedomics. Molecular docking and dynamics simulation revealed that these compounds exhibit superior binding affinities to six core targets. Finally, the expression levels of AKT1, p-AKT1, mTOR, Caspase 3, TLR2, TLR4, ERK1/2, STAT1, MyD88, NFκB, and BCL2 in colon tissues were detected in UC-SDDS rats treated with SLBZP. The study showed that SLBZP effectively treats UC-SDDS rats by modulating multiple components, targets, and pathways using serum pharmacochemistry, network pharmacology, and metabolomics.
Shen B, Yang Z, Pan Y, Yang W, Chen J
Strength of Association: How Useful Is Handgrip Strength as a Functional Biomarker in Patients with Inflammatory Bowel Disease?Editorial Digestive diseases and sciences | 2026-05-06
The real diagnostic value of serum iron in iron deficiency anemia among patients with inflammatory bowel disease: A retrospective study. The Journal of international medical research | 2026-05-06
ObjectiveThe diagnostic utility of serum iron in identifying iron deficiency anemia among patients with inflammatory bowel disease remains underreported. This study aimed to evaluate the true diagnostic value of serum iron.MethodsA total of 160 patients with iron deficiency anemia from a grade-A general hospital in Sichuan Province between January 2022 and January 2025 were enrolled. Eighty patients with inflammatory bowel disease and iron deficiency anemia were included in the test group, while 80 patients with iron deficiency anemia without inflammation were included in the control group. Iron metabolism parameters, including serum iron and serum ferritin, complete blood count indices, and biochemical markers, were collected and compared. Differences in diagnosing iron deficiency anemia using serum iron and serum ferritin among patients with inflammatory bowel disease were compared using the chi-square test. Spearman correlation analysis was performed among serum iron, serum ferritin, and other indicators. Meanwhile, potential factors affecting serum iron levels were investigated using linear regression, and the significance of serum iron in diagnosing inflammatory bowel disease with iron deficiency was evaluated using the receiver operating characteristic curve.ResultsAmong patients with inflammatory bowel disease, ulcerative colitis and Crohn’s disease showed no significant differences in serum iron and serum ferritin levels. The real clinical results showed that when using 1-6.6 times the lower limit of normal of serum ferritin as a threshold to diagnose patients with inflammatory bowel disease and iron deficiency anemia, a statistically significant difference was observed compared with the serum iron lower limit of 1 time (p < 0.01). The positivity rate of iron deficiency anemia was 88.75% (71/80) for serum iron and 61.25% (49/80) for 3.3-time serum ferritin. Correlation analysis revealed that serum iron was positively correlated with serum ferritin (r = 0.263, p = 0.018) and negatively correlated with most inflammatory parameters (p < 0.05). Multiple linear regression analysis showed that when serum iron was used as the dependent variable, the optimal regression model with the independent variables serum ferritin, hemoglobin, platelet count, and monocyte-to-lymphocyte ratio had regression coefficients (β) of 0.246, 0.231, -0.405, and -0.187, respectively, all of which were significantly different (p < 0.05). Moreover, according to the European Crohn’s and Colitis Organization diagnostic criteria for iron deficiency, patients with inflammatory bowel disease were divided into an iron deficiency group involving 41 patients and a non-iron deficiency group involving 39 patients. By comparing the parameters of the two groups and constructing the receiver operating characteristic curve, serum iron alone yielded the highest Youden index and the largest area under the curve for diagnosing iron deficiency (area under the curve = 0.764, p < 0.001). However, when the false-positive rate was controlled at 20%, the sensitivity of serum iron for diagnosing iron deficiency was 62.00%.ConclusionsIn patients with inflammatory bowel disease, serum iron is inversely associated with inflammation and appears to be more sensitive than serum ferritin in detecting iron deficiency anemia. These findings suggest that combined measurement of serum iron and serum ferritin may enhance the diagnosis of iron deficiency anemia in clinical practice.
Tang JT, Wang X, Chen H, He GB
DUSP family phosphatases in cell signaling, inflammation, and chronic diseases.Review Journal of biomedical science | 2026-05-06
Multiple members (DUSP1-29) of dual-specificity phosphatase (DSP) family are key regulators of mitogen-activated protein kinases (MAPKs), which regulate numerous physiological responses. Eight DUSPs are also named MAPK phosphatases (MKPs). DUSP dysregulation contributes to the pathogenesis of various human inflammatory and chronic diseases. Downregulation of DUSP1, DUSP3, DUSP11, and DUSP22, as well as upregulation of DUSP4, DUSP6, and DUSP23 are involved in human autoimmune diseases. Besides autoimmune diseases, reduction of DUSP1, DUSP2, and DUSP14, as well as induction of DUSP8 contribute to the pathogenesis of allergic diseases. Additionally, decreased levels of DUSP2, DUSP11, DUSP22, and DUSP28 are associated with human inflammatory bowel diseases. Moreover, deficiency of 10 DUSPs, as well as induction of DUSP4 are associated with metabolic diseases. Downregulation of 5 DUSPs are involved in cardiovascular disease pathogenesis; in contrast, upregulation of other 5 DUSPs are correlated with cardiovascular diseases. Collectively, dysregulated DUSPs could be diagnostic biomarkers and therapeutic targets for inflammatory diseases. Due to complex expression patterns of DUSPs, it is crucial to study the regulatory mechanisms of individual DUSPs in various inflammatory and chronic diseases. In this review, we summarize the roles and regulatory mechanisms of DUSPs in human inflammatory and chronic diseases. We also discuss the potential therapeutic applications of DUSP agonists/inhibitors in human inflammatory and chronic diseases.
Wang CW, Chuang HC, Tan TH
Spatiotemporal analysis reveals distinct inflammatory programs underlying chronic colitis. Immunity | 2026-05-06
Inflammatory bowel disease (IBD) is a complex disorder that is often resistant to immunomodulatory treatments. Here, to understand how immune, epithelial, and stromal compartments are rewired during disease initiation and progression, we leveraged T cell transfer and Il10-/- spontaneous colitis models, including anti-IL-12p40 intervention, and integrated time-course transcriptomic analyses at bulk, single-cell, and spatial resolution. These well-established models exhibited conserved features of chronic inflammation, including neutrophil infiltration, and impaired tissue regeneration. Comparison of murine transcriptional programs and human IBD datasets revealed neutrophil-associated inflammation and cytokine signaling as the most conserved pathways across species. We identified spatial heterogeneity in inflammatory modules and described three gene programs with differential spatial and temporal distributions, including one corresponding to tertiary lymphoid structures. When used together, these models recapitulate complementary aspects of human disease at both cellular and transcriptional levels. This high-resolution spatiotemporal atlas will guide future translational research aimed at optimizing therapeutic strategies for IBD.
Fransson J, Sorini C, Castillo F, Chi Y, He N, Suarez-Alvarez M, Ulloa MA, Morales Castro RA, Okhovat A, Sounart H
Predicting trajectories of illness using RNA velocity of whole blood.Observational study★ Nature communications | 2026-05-06
Transcriptomic analyses reveal the status of cells, tissues, or organisms, across states of health and disease. RNA velocity adds a temporal dimension to single cell analyses, predicting future transcriptomic and phenotypic states, based on the current spliced and unspliced mRNA of each cell. We hypothesized that RNA velocity could be adapted to predict future clinical state of individuals with acute and chronic illnesses, using their whole-blood transcriptomes. We developed VeloCD, a method for quantitative prediction of transitions in clinical state from a single time-point RNA sample. This predicts transcriptomic trajectories and future infection status in influenza A and SARS-CoV-2 controlled human infection studies, which are consistent with trajectories in naturally acquired infections. In HIV-TB coinfected individuals, VeloCD predicts the onset of immune reconstitution inflammatory syndrome. In individuals receiving biological therapy for inflammatory bowel disease, whole blood RNA velocity after the first dose of treatment indicates whether remission will be achieved by the end of the treatment course. In a multinational observational study of acutely unwell febrile children, VeloCD predicts those with greatest medical care requirements. Our results demonstrate proof-of-concept for the use of RNA velocity to predict trajectories of human diseases.
Dunican C, Wilson C, Habgood-Coote D, Paterson S, Noursadeghi M, Moseki R, Stek C, Wilkinson RJ, Agyeman PKA, Beudeker CR
Dexpanthenol reduces IL 6 and VEGF gene expression in a rat model of acetic acid induced ulcerative colitis. Molecular biology reports | 2026-05-05
Ulcerative colitis is a chronic inflammatory bowel disease characterized by inflammation of the colonic mucosa. This study aimed to evaluate the effects of dexpanthenol in an acetic acid-induced model of colitis in rats. Thirty-two adult male Wistar rats were randomly assigned to four groups: Control (intracolonic saline), dexpanthenol, acetic acid (A.A; 4% acetic acid-induced colitis), and treatment (A.A + dexpanthenol 500). Colitis was induced by intracolonic administration of 4% acetic acid. After 7 days, macroscopic and histopathological evaluations of the colon were performed. The mRNA expression levels of IL-6 and VEGF were assessed using real-time PCR. Stool consistency, colon length, and colon weight-to-length ratio were also measured. Dexpanthenol administration significantly ameliorated acetic acid-induced colitis. The A.A + dexpanthenol group showed partial restoration of colon length, improved stool consistency, and a reduced colon weight-to-length ratio compared with the A.A group. Histopathological analysis demonstrated reduced mucosal damage and decreased inflammatory cell infiltration in dexpanthenol-treated rats. In addition, dexpanthenol significantly decreased IL-6 and VEGF mRNA expression compared with the A.A group (P < 0.0001). Dexpanthenol exerts protective effects against experimental ulcerative colitis in rats by attenuating inflammation, improving tissue integrity, and downregulating IL-6 and VEGF gene expression. These findings suggest its potential as a supportive therapeutic agent in ulcerative colitis.
Shahrooei M, Rahimi K, Givi ME, Rezaie A
Impact of Neutrophils on the Tissue Microenvironment During Intestinal Inflammation.Review Journal of inflammation research | 2026-05-01
Neutrophils (polymorphonuclear leukocytes, PMN) are abundant innate immune cells that rapidly accumulate at mucosal surfaces during inflammation. While their antimicrobial functions are essential for host defense, sustained PMN activation profoundly alters the tissue microenvironment, driving epithelial barrier disruption, ECM remodeling, metabolic imbalance, and microbiome dysbiosis. In chronic inflammatory diseases such as inflammatory bowel disease (IBD), these processes contribute to persistent tissue injury and therapeutic resistance. In this review, we synthesize evidence from human mucosal biopsies, experimental models of intestinal inflammation, and emerging single-cell, spatial, and metabolic approaches to define how PMN shape the inflamed mucosal microenvironment. We highlight mechanisms governing PMN recruitment, retention, and survival; effector programs including reactive oxygen species production, protease release, and PMN extracellular trap formation; and bidirectional crosstalk with epithelial, stromal, and immune cell compartments. We further discuss how PMN-driven metabolic and microbiome alterations reinforce chronic inflammation and influence responses to biologic therapy. Collectively, these insights reframe PMN as context-dependent regulators of mucosal pathology and repair and identify PMN-centered pathways as promising targets for precision therapies aimed at restoring barrier function and promoting durable inflammatory resolution.
Minhajuddin F, Colgan SP, Cartwright IM
Faecal calprotectin in perianal fistula: Can a negative test miss isolated Crohn’s disease?Letter Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland | 2026-05
Integrated single-cell transcriptomics and in vivo investigation reveal the role of ANXA1 in intestinal barrier dysfunction during heat stroke by mediating neutrophil-monocyte interaction and regulating the TLR4/ERK/NF-κB pathway. Biochemical and biophysical research communications | 2026-04-30
Heat stroke (HS) causes high mortality via multiple organ dysfunction syndrome, with intestinal barrier dysfunction as an early trigger of systemic inflammation. However, the roles of annexin A1 (ANXA1) in HS-induced intestinal barrier dysfunction remain unclear. Therefore, this study investigated the roles of ANXA1 in HS-induced intestinal barrier dysfunction through integrating single-cell transcriptomics and in vivo experiments. The single-cell RNA sequencing (scRNA-seq) data were used to analyze the cell subpopulation changes between healthy controls and HS patients, as well as between the inflammatory sites and non-inflammatory sites in inflammatory bowel disease. In vivo, the H&E staining, flow cytometry, ELISA, and Western blot were used to determine the pathological injuries, the proportion of neutrophils and monocytes, inflammatory cytokine levels, and related protein expression levels in the colon tissue. Immunofluorescence co-localization analysis was performed to detect the interaction between ANXA1 and immune cells. The scRNA-seq data showed that the proportion of neutrophil and CD14+Mono subpopulations was increased in HS patients. Concurrently, the ANXA1 expression was significantly upregulated in multiple immune cell subpopulations, including the CD14+Mono, CD16+Mono, mDC, MDSC, and neutrophil subpopulations. Cell-cell communication analysis further demonstrated that the ANXA1-formyl peptide receptor 2 (FPR2) ligand-receptor pairs were the dominant mode of interaction during HS. Importantly, there was partial overlap between cell populations expressing ANXA1 and barrier genes. In addition, ANXA1 was positively associated with M2 monocyte phenotype in both inflammatory and non-inflammatory sites. After establishing the HS model, there were some alterations in the colon tissue, including the exacerbated pathological injuries, upregulated ANXA1 and FPR2 protein expression levels, downregulated ZO-1 and occludin protein expression levels, increased inflammatory cytokine levels, and activated TLR4/ERK/NF-κB pathway. Immunofluorescence co-localization analysis revealed that the mean density of ANXA1, CD14+, and Ly6G in the colon tissue of HS mice was significantly elevated compared with the control group, and the co-localization of ANXA1 with CD14+ and ANXA1 with Ly6G was enhanced. The treatment of Boc1 led to a dramatic reduction in ANXA1 mean density, a further increase in CD14+ and Ly6G mean density, and a reduction in the co-localization of ANXA1 with CD14+ and Ly6G. Apart from reversing the ANXA1 and FPR2 protein expression levels, inhibiting ANXA1 aggravated the damaging effects of HS on the colon tissue. In conclusion, ANXA1 protected against HS-induced intestinal barrier dysfunction by regulating neutrophil-monocyte interaction and inhibiting TLR4/ERK/NF-κB, with ANXA1-FPR2 as a key axis, which offers a novel target and strategy for the clinical treatment of HS-induced intestinal barrier dysfunction.
Li J, Chen X, Tong Z, Jin Y
Opportunistic coronary calcium progression on routine chest CT improves cardiovascular risk stratification in patients with inflammatory bowel disease: a multicenter study. Frontiers in cardiovascular medicine | 2026-04-28
Patients with inflammatory bowel disease (IBD) have increased atherosclerotic cardiovascular risk that may be underestimated by conventional factors. Whether coronary artery calcium (CAC) progression adds prognostic value beyond baseline CAC in IBD is unclear. In this multicenter retrospective cohort, 467 IBD patients without known atherosclerotic cardiovascular disease underwent ≥2 routine non-contrast chest CT scans (mean interval 21.2 months). CAC progression was defined as incident CAC (0 to >0), absolute progression (0 < baseline <100 with annualized increase ≥10), or relative progression (baseline ≥100 with annualized increase ≥10%). Major adverse cardiovascular events (MACE) were the primary outcome; incident atrial fibrillation (AF) was secondary. Cox proportional hazard regression was utilized to estimate hazard ratios (HRs) for time to MACE regarding CAC progression. Incremental value was assessed by C-index and continuous net reclassification improvement (NRI). Over a median follow-up of 37 months, 59 patients had MACE and 41 developed AF. CAC progression occurred in 27.6% and predicted MACE (HR 7.41, P < 0.001), with graded risk (relative HR 10.31; absolute HR 8.14; incident HR 5.22; all P < 0.001). Adding CAC progression to conventional factors improved discrimination (C-index 0.67 vs. 0.73) and reclassification (NRI 0.22, P < 0.001), whereas baseline CAC added modest value (C-index 0.67 vs. 0.68; NRI 0.04, P = 0.021). CAC progression was also associated with incident AF. Opportunistic CAC progression assessment from routine chest CT improves cardiovascular risk stratification in IBD beyond conventional factors and baseline CAC, including among patients with zero baseline CAC.
Zhang Q, Su Y, Song C, Xu T, Liu W, Cao J, Guo B, Wang L, Yue H, Xu C
Connecting polygenic disease risk to cell states and regulatory programs through single-cell chromatin accessibility. bioRxiv : the preprint server for biology | 2026-04-28
Single-cell ATAC-sequencing enables high-resolution mapping of cell states and their putative regulatory elements. The enrichment of genome-wide association study (GWAS) signals within context-specific regulatory regions can reveal disease-relevant cell populations. We present Single-Cell ATAC-seq Disease Score (SCADS), a computational framework that integrates GWAS summary statistics with scATAC-seq data to prioritize disease-relevant cells. SCADS produces calibrated, cell-level scores that are comparable across datasets and traits by: (i) identifying chromatin co-regulatory regions via topic modeling, (ii) quantifying their polygenic GWAS enrichment, and (iii) calculating cell-specific disease scores from topic weights and enrichment levels. Across extensive simulations, SCADS outperforms existing methods in power while controlling false positives. Applied to multiple autoimmune traits, SCADS reveals marked heterogeneity in disease relevance within canonical immune cell types. We specifically studied the differential disease relevance within CD8 + T and colon epithelial cells for inflammatory bowel disease, and pinpointed underlying gene programs and variants. SCADS is scalable, interpretable, and modular, providing a general framework to connect noncoding regulatory variation to cellular identity and function.
Yu L, Deary LT, Liu Q, Zhang Q, Zhao S
Toward a United Arab Emirates national inflammatory bowel disease transition care pathway: Findings from a healthcare professional survey and development of evidence-based tools. Saudi journal of gastroenterology : official journal of the Saudi Gastroenterology Association | 2026-04-24
The transition from pediatric to adult inflammatory bowel disease (IBD) care in the United Arab Emirates (UAE) is unstructured, creating a critical gap that risks treatment nonadherence and abrupt, unstructured transfers into adult services. We aimed to assess national practice patterns and barriers to inform development of a standardized UAE National IBD Transition Care Pathway. A 45-item electronic survey was distributed to UAE gastroenterologists and IBD nurse specialists via the Emirates Gastroenterology and Hepatology Society (EGHS) networks. We analyzed demographics, current practices, and perceived barriers, performing cross-tabulations between pediatric and adult healthcare professionals. Fifty-five healthcare professionals responded (46 adult gastroenterologists, 7 pediatric gastroenterologists, 2 IBD nurse specialists). Only 5.5% reported having a consistently used formal transition policy, while 58.2% had no policy. Joint pediatric-adult clinics were unavailable in 81.8% of practices. The highest-rated barriers included lack of a formal transition program (mean 3.65/5, 54.5% rating significant/very significant), patient inability to afford medications (3.40, 49.1%), and difficulty navigating public-private sectors (3.25, 47.3%). Adult healthcare professionals tended to rate barriers higher, with significant differences for poor communication between teams ( P = 0.020) and medication affordability ( P = 0.016). Healthcare professional priorities were development of a standardized national pathway (78.2%) and unified handover templates (49.1%). This first national assessment confirms critical infrastructure and communication gaps in UAE IBD transition care. In response, the EGHS Task Force has developed a comprehensive toolkit, including a standardized medical handover template, clinical transition framework, and the first Arabic-language Transition Readiness Assessment Questionnaire to standardize clinical practice.
Quraishi MN, Bitar R, El Ouali S, Nathwani RA, Koutoubi Z, Jazzar A, El-Gazzar Y, Al Awadhi S, Al Hassani A, Omar NM
Integrated transcriptome and single-cell RNA sequencing identifies small GTPase-associated biomarkers in ulcerative colitis. Frontiers in immunology | 2026-04-22
Ulcerative colitis (UC) is a chronic, multifactorial inflammatory bowel disease. The involvement of small GTPase-related genes (SGRGs) in UC remains poorly defined. This study aims to identify SGRGs associated with UC and elucidate the molecular mechanisms by which they regulate the pathological progression of UC. Multiple transcriptomic datasets were integrated to identify candidate SGRGs in UC. Four machine learning algorithms were utilized for biomarker screening, followed by the construction of a diagnostic nomogram. The robustness of the identified biomarkers and the nomogram was rigorously evaluated through external validation in multiple independent cohorts. Furthermore, the associations between biomarkers and clinical severity, as well as their capacity for differential diagnosis (UC vs. Crohn’s disease (CD)), were assessed. Functional enrichment, immune infiltration, and cross-dataset single-cell RNA sequencing (scRNA-seq) were employed for in-depth mechanistic investigation. In vivo experiments validated core gene expression. Three biomarkers (ARHGEF3, S100A8, and RHOU) were successfully identified and validated across multiple independent cohorts. The nomogram constructed based on these biomarkers exhibited excellent diagnostic performance (AUC = 0.991 in the training set, 0.938 and 0.968 in the external validation cohort). Notably, the expression levels of these biomarkers significantly correlated with clinical severity and pathological mucosal states, demonstrating their capacity to reflect disease activity and monitor progression. Furthermore, among the identified biomarkers, ARHGEF3 significantly differentiated UC from CD (p < 0.05), while all three markers exhibited discriminative potential with AUC values exceeding 0.6. Functional annotation illustrated that they were commonly enriched within pathways encompassing “Tight junction” and “Leukocyte transendothelial migration”. Immune infiltration assessment demonstrated 27 differentially expressed immune cells (DEICs) among the UC and control groups. Cross-dataset scRNA-seq analysis further confirmed that macrophages were the key cells, exhibiting significant metabolic reprogramming and functional heterogeneity in UC. In vivo experiments confirmed the expression of above biomarkers in UC. This study systematically identifies ARHGEF3, S100A8, and RHOU as novel UC diagnostic biomarkers, implicating them in disease progression via immune regulation and macrophage function. These findings provide a new basis for precise diagnosis and targeted therapy.
Chen M, Dong W
Advances in research on the effects of bile acids and their receptors on intestinal function.Review Frontiers in nutrition | 2026-04-21
Bile acids (BAs), once regarded primarily as detergents facilitating lipid digestion, are now recognized as pivotal signaling molecules that orchestrate intestinal and systemic physiology through a diverse network of nuclear and membrane receptors, with distinct receptor classes mediating complementary transcriptional and rapid signaling responses, including Farnesoid X Receptor (FXR), Takeda G protein-coupled Receptor 5 (TGR5), Pregnane X Receptor (PXR), Peroxisome Proliferator-Activated Receptor α (PPARα), Vitamin D Receptor (VDR), and Mas-related G protein-coupled Receptor member X4 (MRGPRX4). This review synthesizes recent advances in understanding the molecular architecture of BA signaling, emphasizing receptor structural diversity, spatiotemporal expression patterns along the gastrointestinal tract, ligand specificity shaped by BA chemical modifications, and the emerging roles of microbiota-derived bile acid derivatives and selected non-canonical host targets in intestinal immune and metabolic regulation. Central to this signaling axis is the gut microbiome, which enzymatically reprograms the BAs pool through deconjugation, dehydroxylation, oxidation, and epimerization, as well as emerging reconjugation/amidation pathways, thereby generating classical secondary BAs as well as structurally novel metabolites that modulate host receptor activity and immune-cell programs. In turn, BAs shape microbial composition, establishing a dynamic bidirectional feedback loop critical for maintaining intestinal homeostasis. In addition to classical receptor signaling, selected microbiota-derived BAs metabolites can also influence immune-associated transcriptional regulators, thereby expanding the scope of BAs signaling in mucosal immune homeostasis. Beyond metabolism, BAs-receptor interactions integratively regulate gut barrier integrity via tight junction reinforcement, modulate immune responses through anti-inflammatory pathways and tolerogenic cell induction, and influence gut motility and neuroendocrine signaling. Dysregulation of BAs receptor and metabolite-mediated signaling axes is increasingly implicated in the pathogenesis of inflammatory bowel disease, bile acid malabsorption, diarrhea-predominant irritable bowel syndrome, colorectal cancer-via DNA damage and Wnt/β-catenin pathway activation-and systemic conditions such as obesity, non-alcoholic fatty liver disease, and sepsis-related intestinal injury. Emerging therapeutic strategies aim to restore BAs signaling balance through next-generation receptor modulators, tissue-targeted delivery systems, microbiome-directed interventions, rational use of sequestrants, and synergistic combination therapies, thereby supporting the development of more precise and mechanism-based interventions. Future progress will hinge on interdisciplinary approaches integrating metabolomics, gnotobiotic models, and clinical translation to harness the full therapeutic potential of the BAs signaling network in gastrointestinal and metabolic health.
Cheng Y, Zhang L, Zhang M, Yu J
Pathogenesis & Basic Science (12 papers)
Drugst.One DREAM-Drug repurposing through expert annotation and modification.★ British journal of pharmacology | 2026-05-10
Complex diseases often lack an actionable understanding of their underlying causal biological mechanisms, which leads to treating symptoms rather than causes. Network and systems medicine define disease mechanisms through disease-associated genes, their encoded proteins and their protein-protein interactions (PPIs), thus forming disease modules. Complex diseases can be subdivided into actionable causal mechanisms for potential precision and curative therapy by repurposing small-molecule drugs for new indications. However, current computational methods for disease module construction overlook pathway annotations, cellular compartments and directed PPIs. Consequently, disease modules require contextual refinement to identify dysregulations, select appropriate drug classes and eliminate promiscuous proteins. Here, we present Drugst.One DREAM, which equips biomedical experts with a user-friendly toolbox for disease module refinement that does not require bioinformatics expertise. This extension of the web tool Drugst.One introduces network editing features. Users can refine PPI modules supported by pathway enrichment analysis and network clustering. Dedicated graph layouts highlight subcellular localisation and causal relationships queried from OmniPath. We demonstrate our tool by reproducing a previously described NOX5-containing module and refining an algorithmically inferred candidate module for Crohn’s disease, showcasing its effectiveness in refining disease modules for a broad user group in pharmacology and biomedical research. The Drugst.One DREAM extension closes an important gap in the network medicine tool landscape by offering experts a user-friendly option for refining disease modules.
Spindler LM, Kersting J, Manz Q, Hartung M, Maier A, Mamdouh ZM, Casas AI, Baumbach J, List M
Lacticaseibacillus paracasei 18 effectively ameliorates dextran sodium sulfate-induced colitis in mice through regulating gut microbiota metabolite-mediated PI3K/AKT/NF-κB signaling pathway. International immunopharmacology | 2026-05-09
Ulcerative colitis (UC) is a persistent inflammatory bowel disorder marked by mucosal inflammation and dysbiosis of the gut microbiome. Lacticaseibacillus paracasei 18 (LP18) is a versatile carbohydrate-degrading bacteria that may work as a probiotic to improve gut health by modulating gut microbiota. However, its exact function and mechanisms in UC remain ambiguous. This research employed integrated microbiome, metabolome, and transcriptome analysis to investigate the therapeutic benefits and underlying mechanisms of Lacticaseibacillus paracasei on dextran sulfate sodium (DSS)-induced colitis in murine models. After the intervention of LP18, colitis mice demonstrated an improvement in body weight loss and a mitigation of colonic shortening, accompanied by a moderate increase of expressions in colonic tight junction-related genes (Claudin-1, Claudin-2, Claudin-5, ZO-1, and Occludin). Additionally, LP18 improved the structure and diversity of the gut microbiota in these DSS-induced mice. Metabolomic study suggested that LP18 substantially influenced the intestinal metabolic profile, particularly compounds associated with tryptophan metabolism. The metabolic alterations were closely linked to the enhancement of the microbial community makeup. The analysis of colon RNA sequencing indicated that, in comparison to the DSS group, LP18 significantly downregulated various immune-related signaling pathways, especially the PI3K/AKT/NF-κB pathways. Correlation analysis of microbiota, metabolism, and genes uncovered a substantial association between the taxa enhanced by LP18 and the critical genes in the NF-κB signaling pathways. Overall, the integrated analysis of multiple omics approaches revealed that LP18 may function as a probiotic therapeutic agent for UC. It represents novel dietary and therapeutic strategies for controlling UC through the regulation of gut microbiota, modification of metabolic profiles, reinforcement of the intestinal barrier, and downregulation of the PI3K/AKT/NF-κB signaling pathway.
Lu W, Liu Y, Hao H, Li X, Hou G, Zhang J, Li W, Wang Q, Huang Q
Isoliquiritigenin suppresses ER stress-driven epithelial apoptosis to preserve barrier integrity in colitis. Toxicology and applied pharmacology | 2026-05-07
Ulcerative colitis (UC) is an inflammatory bowel disease characterized by epithelial barrier disruption and chronic mucosal inflammation, and its underlying mechanisms remain incompletely understood. Increasing evidence suggests that endoplasmic reticulum (ER) stress contributes to epithelial injury and apoptosis and plays an important role in the development of UC. Isoliquiritigenin (ISL), a natural flavonoid derived from licorice, has been reported to exert anti-inflammatory and antioxidant effects. However, whether ISL alleviates UC by regulating ER stress-associated apoptosis and the underlying mechanisms remain unclear. This study aimed to determine whether ISL alleviates dextran sulfate sodium (DSS)-induced colitis by regulating ER stress-associated apoptosis and to explore the underlying molecular mechanisms. A DSS-induced colitis model was established in mice, and ER stress was induced in Caco-2 cells using tunicamycin. Disease severity was evaluated by disease activity index scoring, histological examination, mucus production assessment, and intestinal permeability analysis, and inflammatory cytokine levels were measured. Quantitative proteomics was performed to identify altered pathways. ER stress signaling and apoptosis-related proteins were further examined. In addition, the ER stress inhibitor 4-phenylbutyric acid (4-PBA) was used to verify the involvement of ER stress. The results showed that ISL markedly alleviated DSS-induced colitis, as evidenced by improved epithelial structure, mucus production, and barrier function, along with reduced levels of IL-6, IL-1β, TNF-α, and IL-17 A. Proteomic analysis revealed enrichment of ER protein processing and apoptosis-related pathways in DSS-treated tissues, which were partially reversed by ISL. DSS induced ER stress, as indicated by increased GRP78 (BiP) expression and activation of the PERK-eIF2α-ATF4-CHOP pathway, and promoted epithelial apoptosis, evidenced by Bax upregulation, caspase-3 activation, Bcl-2 reduction, and increased TUNEL-positive cells. ISL inhibited activation of this pathway and restored apoptotic balance. Consistently, ISL suppressed tunicamycin-induced ER stress, barrier dysfunction, and apoptosis in Caco-2 cells, whereas pharmacological inhibition of ER stress with 4-PBA produced similar protective effects. Collectively, these findings suggest that ISL attenuates DSS-induced colitis by inhibiting ER stress-mediated epithelial apoptosis, potentially through modulation of the PERK signaling pathway, thereby providing experimental evidence for its therapeutic potential in UC.
Xu C, Wang H, Zhu M, Fan Z
Euphorbia humifusa Willd. alleviates ulcerative colitis by inhibiting lipid peroxidation via ACSL4/COX-2 axis. Journal of ethnopharmacology | 2026-05-07
Herba Euphorbiae Humifusae (Euphorbia humifusa Willd., EH), named Dijincao, a traditional Chinese herbal medicine used to treat dysentery and enteritis, shows therapeutic potential for ulcerative colitis (UC), yet its mechanism remains unclear. To elucidate the efficacy of EH against UC and its mechanism. The effect of EH extract (EHE) on UC was evaluated using DSS-induced mice. Integrated analysis of metabolomics and network pharmacology based on the colonic exposure of prototypes in EHE predicted key targets and pathways involved in the treatment of UC, while molecular docking and biological experiments investigated the mechanism. Spearman’s correlation analysis identified key anti-UC active components, followed by in vitro activity and mechanistic validation in RSL3-induced HCT116 cells and intestinal organoid models. EHE alleviated UC mice in a dose-dependent manner. Network pharmacology predicted the major targets of the 18 colonic exposure components in EHE to be signaling pathways involved in inflammation and lipid metabolism. Metabolomics revealed that EHE primarily regulated glutathione metabolism and arachidonic acid metabolism. Through the integrated analysis of network pharmacology and metabolomics, suggesting that lipid peroxidation involving 11 pivotal targets may mediate the beneficial effect of EHE against UC, while molecular docking analysis and experiments substantiated that the amelioratory action of EHE partially contributed to its inhibition on ACSL4/COX-2 axis mediated lipid peroxidation. Notably, quercetin, kaempferol and naringenin, as key active constituents of EHE against UC, demonstrated the direct regulatory effect on ACSL4/COX-2 axis mediated lipid peroxidation in vitro, which was attenuated upon treatment with overexpressed ACSL4. This study demonstrated that EH ameliorates UC by modulating ACSL4/COX-2 axis mediated lipid peroxidation, thereby enhancing our understanding of the mechanism underlying EH against UC.
Dai P, Zheng B, Pan X, Fan B, Zou Y, Yao Y, Zhang K, Zhou R, Wang M, Zhu C
Effect of Intravesical Administration of Steroid Enemas on an Experimental Autoimmune Interstitial Cystitis-Like Mouse Model. Neurourology and urodynamics | 2026-05-07
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic, non-bacterial cystitis presenting with bladder pain, frequent urination, and Hunner’s lesions. Current therapies, including dimethyl sulfoxide (DMSO) instillation, provide temporary relief but often cause procedural pain. Steroid enemas, used for ulcerative colitis and suitable for self-administration, may offer a novel intravesical treatment option. An experimental autoimmune interstitial cystitis (EAIC) mouse model was induced by immunization with bladder homogenate. Four weeks later, EAIC mice received intravesical phosphate-buffered saline (PBS), 50% DMSO, or a steroid enema formulation containing prednisolone phosphate (Predonema®). Controls received PBS. Outcomes included locomotor activity, cystometry, histopathology, and bladder gene expression by RT-qPCR. EAIC mice showed increased locomotor activity, shortened bladder contraction intervals, urothelial irregularity, and upregulated inflammatory cytokines (IL-1β, IL-6), chemokines (CCL2, CXCL1, CXCL10), COX-2, NGF, VEGF-A, vimentin, and uroplakin-2. DMSO transiently reduced locomotor activity, worsened epithelial thickening, cellular infiltration, and decreased body weight. In contrast, steroid enema instillation preserved urothelial architecture, reduced inflammation, suppressed gene upregulation, normalized bladder function, and alleviated hyperactivity without adverse effects. EAIC mice reproduce pathological and functional features of IC/BPS. Intravesical steroid enema administration showed superior anti-inflammatory and functional benefits compared with DMSO, without apparent tissue damage or disease-associated hyperactivity. Although the effectiveness of steroid enemas might be partially influenced by the effect of thickening agents used as enema additives, this approach could represent a practical, patient-friendly therapy for IC/BPS, supporting further preclinical and clinical evaluation.
Sugaya K, Nishijima S, Kadekawa K, Ashitomi K, Matsumoto S
Bee venom acupuncture therapy ameliorates ulcerative colitis by reducing inflammatory response, oxidative stress, and suppressing the NF-κB/HIF-1α pathway. Open life sciences | 2026-05-05
Ulcerative colitis (UC) is a chronic inflammatory bowel disease that poses a significant challenge to public health due to its relapsing nature and complex pathogenesis. This study investigated the protective effects of bee venom acupuncture on UC and explored the underlying mechanisms using a rat model of UC. The findings demonstrated that bee venom acupuncture significantly restored body weight, reduced disease activity index (DAI) scores, and ameliorated colonic tissue injury. Moreover, bee venom therapy decreased serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-8 (IL-8), and downregulated their protein expression in colon tissue. Furthermore, assessment of oxidative stress biomarkers revealed that bee venom treatment significantly reduced reactive oxygen species (ROS) and malondialdehyde (MDA) levels while elevating superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT) levels in the colon. Western blot and immunohistochemistry analyses indicated that bee venom treatment inhibited NF-κB/HIF-1α pathway. In conclusion, bee venom acupuncture ameliorates UC by reducing inflammatory responses, alleviating oxidative stress, and suppressing NF-κB/HIF-1α pathway, suggesting its potential as a therapeutic strategy for UC management.
Liang J, Ma X, Ren Y, Chen M, Ma H, Guo J
Mechanism of recombinant Trichinella spiralis antigen p53 alleviating experimental colitis via the IDO-AhR Axis. International immunopharmacology | 2026-05-05
Inflammatory Bowel Disease (IBD) is a chronic inflammatory disorder characterized by disrupted intestinal immune homeostasis. Emerging evidence indicates that parasitic infections may exert anti-inflammatory effects by modulating host immunity, although the underlying molecular mechanisms remain incompletely elucidated. This study aimed to investigate whether recombinant Trichinella spiralis (T. spiralis) antigen p53 (rTs p53) protects against experimental colitis by regulating the indoleamine 2, 3-dioxygenase (IDO)-aryl hydrocarbon receptor (AhR) axis. In vitro assays were performed to evaluate the effects of rTs p53 on IDO expression in dendritic cells (DCs), the kynurenine/tryptophan (Kyn/Trp) ratio, cytokine secretion, and regulatory T cell (Treg) frequency. Specific inhibitors were used to functionally validate the IDO and AhR pathways. In a dextran sulfate sodium (DSS)-induced mouse model of chronic colitis, the therapeutic efficacy of rTs p53 was assessed comprehensively using the disease activity index, colon length, histopathological scoring, myeloperoxidase (MPO) activity, cytokine levels, and flow cytometric analysis of immune cell populations. Mechanistic validation was further conducted in vivo and in vitro by combined administration of the IDO inhibitor 1-MT and the AhR antagonist CH-223191. In vitro, rTs p53 stimulation significantly upregulated IDO expression in DCs, elevated the Kyn/Trp ratio, promoted CD4+ T cell differentiation into Tregs, and suppressed Th17 polarization through activation of the AhR pathway. These effects were abrogated by the IDO inhibitor 1-MT or the AhR antagonist CH-223191. In mice with DSS-induced colitis, rTs p53 treatment markedly ameliorated disease activity, alleviated colonic histopathological damage, downregulated proinflammatory cytokine levels, and restored the Treg/Th17 balance. Notably, co-administration of 1-MT or CH-223191 significantly attenuated these protective effects. This study demonstrates that rTs p53 promotes Trp catabolism toward Kyn by activating the IDO-AhR signaling axis in DCs. This mechanism regulates the Treg/Th17 balance, suppresses intestinal inflammatory responses, and ultimately mitigates experimental colitis. These findings provide a novel perspective for clarifying the mechanisms of parasite-derived immunomodulatory molecules and offer experimental evidence for the development of IDO-AhR-targeted therapeutic strategies against IBD.
Yuan X, Li W, Li L, Han C
Eosinophil-derived COX-2 protects against experimental colitis through the PGE2-IL-22 axis. Proceedings of the National Academy of Sciences of the United States of America | 2026-05-04
Inflammatory bowel disease (IBD) is driven by a breakdown in immune regulation and epithelial barrier function, yet the contribution of eosinophils to this process has remained poorly defined and controversial. While eosinophils infiltrate the intestinal mucosa during both flares and remission, their role in shaping disease outcomes is unclear. Our RNA-seq analyses of colonic eosinophils isolated from dextran sulfate sodium (DSS)-treated mice revealed a significant upregulation of cyclooxygenase (COX)-2 (gene name, Ptgs2). Eosinophil-specific deletion of COX-2 (Ptgs2fl/fleoCre+/-) reduced IL-22 production and exacerbated DSS- and trinitrobenzene sulfonic acid (TNBS)-induced colitis, characterized by greater weight loss, higher disease activity, colon shortening, and epithelial injury. Administration of recombinant IL-22 reversed these phenotypes. Mechanistically, eosinophil-derived COX-2 enhanced IL-22 production by type 3 Innate lymphoid cells (ILC3s) through prostaglandin E2 (PGE2) signaling. Consistently, Ptgs2fl/fleoCre+/- mice exhibited reduced colonic PGE2 levels, while PGE2 analog treatment restored IL-22 production and mucosal protection. Our findings identify eosinophil-derived COX-2 and PGE2 as a critical regulator of IL-22 production during colitis, uncovering a eosinophil-ILC3 cross talk that safeguards the intestinal barrier and represents a promising therapeutic target in IBD.
Yang Y, Atkins CL, Fan Y, Hou L, Zhao J, Gao J, Wen Y, Moreno NF, Huang X, Bishehsari F
Comparative pharmacodynamic material basis of oral and colonic administration of Baitouweng decoction in experimental ulcerative colitis. Journal of ethnopharmacology | 2026-05-04
Baitouweng Decoction (BTWD) is a traditional Chinese medicine formula widely used in clinical practice for treating ulcerative colitis (UC). However, its precise therapeutic mechanisms remain unclear. This study investigates the therapeutic effects of BTWD administered via colon and oral routes in a UC model induced by fecal microbiota transplantation (FMT) and dextran sodium sulfate (DSS). It further explores the distinct pharmacological mechanisms associated with each route of administration. Male rats with UC induced by human-derived FMT and DSS were treated with BTWD via oral or colonic administration. Therapeutic outcomes were evaluated through clinical indicators and histopathology. Drug metabolites in serum and colon contents were analyzed by Ultra Performance Liquid Chromatography-Q Exactive-Orbitrap Mass Spectrometer (UPLC-QE-Orbitrap MS). Serum and fecal metabolomics identified disease-related biomarkers. Potential active substances were screened by correlating serum and fecal biomarkers with BTWD-derived components. Key active substances and targets were identified through network pharmacology and molecular docking, clarifying the pharmacological basis of each administration route. Surface plasmon resonance (SPR) and Western blot were performed to experimentally validate the binding interactions and target protein expression. Both administration routes of BTWD significantly alleviated UC symptoms. Compared to the model group, BTWD-treated rats exhibited reduced weight loss, lower disease activity index (DAI) scores, and recovered colon length. Serum levels of pro-inflammatory cytokines IL-6, IL-17, and IL-1β were decreased, while anti-inflammatory IL-10 was increased. Expression of Occludin and MUC2 proteins in colon tissue was significantly upregulated. In total, 82 serum and 70 colon components were identified following oral administration, while colonic administration yielded 73 serum and 78 colon components. Correlation analysis screened 36 active components associated with colonic administration and 25 with oral administration. Network pharmacology and molecular docking suggested that core components from colon administration (Anemoside B4, Betulonic acid) may act via targets such as EGFR, LCK, and MET, while oral components (Berberine, Oxyepiberberine) may target AURKA, MET, and PTGS2. SPR confirmed direct binding of anemoside B4 and berberine to EGFR with KD values of 9.47E-04 M and 2.96E-04 M, respectively. Western blot revealed route-dependent modulation of EGFR, PTGS2, LCK and AURKA expression, corroborating the predicted targeting. BTWD is effective in treating UC through both colonic and oral administration. This study provides a comprehensive “efficacy-component-metabolism-target” analysis that reveals distinct pharmacological mechanisms underlying each administration route. These findings support the traditional use of BTWD and offer a theoretical foundation for developing optimized, route-specific therapies for UC.
Liu T, Zhao Y, Wang X, Ding L, Yu G, Lin X, Wu X
MiR-155 knockout alleviates colitis exacerbated by EHDPHP exposure through inhibition of the JAK-STAT-p53 axis and apoptosis.★ Journal of hazardous materials | 2026-04-28
The increasing environmental concentration of the organophosphate ester 2-ethylhexyl diphenyl phosphate (EHDPHP) poses a threat to global health, particularly for individuals with preexisting conditions such as inflammatory bowel disease (IBD). This study investigated the impact of EHDPHP on a dextran sulfate sodium (DSS)-induced colitis mouse model. We found that EHDPHP exposure significantly aggravated disease severity and was associated with a marked upregulation of microRNA-155 (miR-155) in the colon. To elucidate the role of miR-155 in this process, we utilized miR-155 gene knockout (miR-155-/-) mice. Our results demonstrate that miR-155 knockout protected against EHDPHP-exacerbated colitis by inhibiting apoptosis and suppressing the proinflammatory JAK-STAT-p53 signaling axis, and this process is closely linked to shifts in gut microbiota abundance. Conversely, miR-155 overexpression reverses these protective effects. These findings establish miR-155 as a critical mediator in the aggravation of colitis by environmental pollutants and suggest that targeting miR-155 may represent a potential therapeutic target for pollutant-aggravated inflammatory bowel disease.
Hsu C, Li XW, Liu JL, Zeng JH, Chen L, Yang JZ, Liu Y, Li JH, Li JH, Chen LJ
Eupalinolide B alleviates ulcerative colitis by targeting HMGB1 through modulation of the HMGB1/TLR4/MyD88/NF-κB signaling pathway.★ Phytomedicine : international journal of phytotherapy and phytopharmacology | 2026-04-25
Ulcerative colitis (UC) is a chronic, relapsing inflammatory bowel disease with limited therapeutic options. Eupalinolide B (EB), a guaianolide sesquiterpene lactone derived from Eupatorium lindleyanum DC., exhibits anti-inflammatory and immunomodulatory activities. This study investigated the therapeutic potential and mechanism of EB against UC. In vitro anti-inflammatory effects of EB were assessed in LPS-induced RAW264.7 and IEC-6 cells by measuring NO production and inflammatory cytokine mRNA levels (IL-6, IL-1β, TNF-α). In vivo, a DSS-induced UC mouse model was used to evaluate EB’s efficacy through body weight, DAI score, immunohistochemistry, and inflammatory factor levels. Target identification employed activity-based protein profiling (ABPP) with an EB-based probe, followed by validation via pull-down, CETSA, SIP, and immunofluorescence assays. Binding affinity and site were characterized using isothermal titration calorimetry (ITC), LC-MS/MS, molecular docking, and mutagenesis. Molecular mechanism was explored by analyzing HMGB1/TLR4/MyD88/NF-κB pathway by WB, qPCR and co-precipitation. EB exerted anti UC effects by alleviating inflammation and enhancing intestinal barrier integrity in vitro and in vivo. Using ABPP, high mobility group box-1 protein (HMGB1) was established as a high-confidence target of EB, characterized by the covalent binding of Cys106 residue. Mechanistically, EB suppressed the TLR4/MyD88/NF κB pathway and disrupted HMGB1 TLR4 interaction. EB ameliorates UC and exerts anti-inflammatory effects by targeting HMGB1 at Cys106 residue. By downregulating HMGB1 protein expression and reducing the binding affinity between HMGB1 and TLR4, EB inhibits the TLR4/MyD88/NF-κB signaling pathway. This study provides theoretical support for the development of EB as a potential anti-UC candidate drug.
Luo W, Zhuang Y, Shen S, Wang Y, Zhu Y, Liu Y, Zhang S, Zhang J, Li S, Zhong L
Modified gegen qinlian decoction ameliorates Veillonella parvula-exacerbated ulcerative colitis via restoration of intestinal mucosal barrier function. Frontiers in pharmacology | 2026-04-21
Ulcerative colitis (UC) is being increasingly connected to the pathogen Veillonella parvula (V. parvula). Modified Gegen Qinlian Decoction (MGQD), a traditional Chinese medicine therapy, is used to treat UC. However, the underlying mechanism by which V. parvula exacerbates UC and whether MGQD can alleviate it is unknown. MGQD therapy was tested on pathogen-free and pseudo-germ-free mice infected with V. parvula. Colitis severity was determined by disease activity index, colon length, and histology. Transmission electron microscopy, Western blot, immunofluorescence, and immunohistochemistry were used to assess the integrity of the intestinal mucosal barrier. In vitro, mouse colonic organoids were utilized to examine the effects of baicalin and puerarin on inflammation-induced downregulation of Muc2 and ZO-1. MGQD therapy dramatically reduced the severity of colitis in both mouse models. MGQD restored the integrity of the mucus and mechanical barriers. Furthermore, baicalin and puerarin reduced inflammation-induced downregulation of Muc2 and ZO-1 in mouse colonic organoids. These findings demonstrate that MGQD alleviates intestinal barrier dysfunction caused by V. parvula, providing novel mechanistic insight for the management of chronic colitis.
She M, Dai X, Wang X, Wang Z, Zhang J, Shi Z, Peng Y, Li X, Chen T, Tang X
Surgery & Complications (11 papers)
Disease phenotype affects treatment of late-onset inflammatory bowel disease: Analysis of a large UK cohort.★ Inflammatory bowel diseases | 2026-05-08
The incidence of inflammatory bowel disease (IBD) in older adults is rising. Studies of late-onset (LO) (diagnosis ≥60 years of age) IBD are contradictory, with some suggesting increased use of corticosteroid and reduced use of advanced therapies. This multicenter study assessed disease phenotype and therapeutic choice in LO-IBD. Patients recruited to the NIHR IBD BioResource with LO ulcerative colitis (UC) or Crohn’s disease (CD) were compared with those with young-onset (YO) (16-39 years of age) and mid-onset (MO) (40-59 years of age) IBD. Medication use and surgeries were assessed in propensity score-matched cohorts. A total of 32 012 patients were studied: 16 930 UC (2247 LO) and 15 082 CD (1409 LO). LO-UC was mostly left-sided, with less isolated proctitis. LO-CD patients had less ileocolonic and perianal disease. Corticosteroid, immunomodulator, and anti-tumor necrosis factor α (anti-TNF) use was lower in LO-UC and LO-CD; however, there was no difference in time to colectomy (LO-UC) or intestinal resection (LO-CD) compared with younger patients. LO-CD patients were more likely to receive vedolizumab and ustekinumab than YO-CD (odds ratio, 0.34 [95% confidence interval, 0.18-0.61] and 0.29 [95% confidence interval, 0.09-0.76], respectively). LO patients with perianal CD were less likely to receive anti-tumor necrosis factor or undergo perianal surgery than YO and MO patients with perianal CD (all P < .01). LO-IBD has a distinct phenotype, with less isolated proctitis (LO-UC) and less ileocolonic and perianal CD. LO-IBD patients had lower corticosteroid, immunomodulator, and anti-tumor necrosis factor use but equivalent colectomy and intestinal resection rates. LO-CD is notable for the higher use of vedolizumab and ustekinumab, suggesting that age, comorbidity, and disease phenotype affect biologic choice in older adults. Research to understand whether differential treatment of older adults is justified is crucial. Disease phenotype and treatment differ in late-onset inflammatory bowel disease compared with younger patients. Late-onset ulcerative colitis and Crohn’s disease patients receive less corticosteroid, immunomodulator and anti-tumor necrosis factor therapy, but have equivalent requirements for colectomy and intestinal resection. Late-onset Crohn’s disease patients receive more vedolizumab and ustekinumab.
Foulser PFG, Martinez-Gili L, Balarajah S, Sundramoorthi R, Alexander JL, Mullish BH, Marchesi JR, Parkes M, Orchard TR, Hicks LC
A gut vascular barrier damage-based scoring system predicts postoperative outcomes in Crohn’s disease. BMC gastroenterology | 2026-05-08
The gut vascular barrier (GVB) is essential for maintaining intestinal homeostasis. However, its role in patients undergoing surgery for Crohn’s disease (CD) remains unclear. Thus, our study aimed to explore the association between GVB and disease severity and postoperative outcomes in CD patients, as well as to develop a scoring system to predict postoperative prognosis. Endothelial plasmalemma vesicle-associated protein (PV-1) is a typical biomarker of GVB dysfunction. The expression of PV-1 was measured in intestinal mucosa of patients with Crohn’s disease (CD) and controls scheduled for surgery. The correlation between PV-1 expression and clinical data was analyzed. Moreover, a scoring system based on PV-1 was developed to predict the postoperative outcomes. GVB damage was detected in CD patients. Levels of intestinal PV-1 expression were markedly higher in inflamed parts of CD patients than in non-inflamed parts and in control patients (both P < 0.05). Levels of PV-1 were positively correlated with preoperative disease activity indexes and postoperative clinical outcomes. Importantly, a new scoring system based on PV-1 was established to predict an adverse total postoperative prognosis or a longer length of stay, and it showed better discrimination (Areas under the receiver operating characteristic curves (AUCs) = 0.808, 0.902, P < 0.001). GVB damage was found in CD patients and was associated with the severity of disease and postoperative outcomes. A scoring system based on GVB damage is promising in predicting poor postoperative outcomes.
Chen XJ, Guo Y, Peng H, Zhang HF, Zhang YN, Liu ZM, Zhang XY
Antibiotic Utilization for Perianal Fistulizing Complications Among Young Patients with Crohn’s Disease. The Journal of pediatrics | 2026-05-07
To characterize patterns of antibiotic use among children with Crohn’s disease (CD) and perianal fistulizing complications (PFCs) via a large, national administrative database. Retrospective analysis of US administrative claims including patients ≤21 years with CD diagnosed 2009-2018 and 5-years of continuous enrollment. We evaluated patient characteristics, medication dispensing, and disease outcomes. Multivariable negative binomial regression evaluated predictors of days of antibiotics dispensed. 5,277 patients were included, with median age 16.0 years at diagnosis (55% male, 77% commercial insurance, 61% White). In total 17% developed PFC during enrollment. Antibiotic dispensing was common, 83% had at least 1 antibiotic prescription. Patients with PFC had more antibiotic days (median 67 days, interquartile range [IQR] 26-138) compared with those without PFC (median 27 days, IQR 10-63; p = 0.001). In an adjusted model, patients with PFC had 90% more antibiotic dispensing than those without PFC. PFCs are common and are associated with greatly increased antibiotic dispensing with 1 in 12 patients filling >20 prescriptions during the 4-year study period. The optimal use of antibiotics remains unclear, and their extensive use in this population emphasizes the need for evidence-based treatment strategies and approaches to antibiotic stewardship.
Gadepalli S, Tribble A, Rahman M, Manning L, Adler J
Εsophageal Crohn’s disease in adults: A systematic review of the literature.Review Surgery | 2026-05-07
Esophageal involvement in Crohn’s disease is rare and poorly understood, presenting with nonspecific symptoms that contribute to delayed diagnosis and inconsistent management. This systematic review aims to characterize the clinical presentation, diagnostic pathways, and treatment approaches for adult patients with esophageal Crohn’s disease. A systematic search of PubMed and Scopus was conducted through May 2025 to identify studies reporting on adult patients with esophageal Crohn’s disease. Descriptive statistics, univariate comparisons, and post hoc pairwise testing with Bonferroni correction were performed. Ninety studies, involving 100 adult patients (54% women; median age, 38 years), were included. The most common primary location was ileocolic (31%), and 20% of the study population had isolated upper gastrointestinal involvement. Dysphagia was the most frequent symptom (41%). Endoscopic diagnosis was made in 98% of patients, with predominant findings of ulcers (70%) and strictures (37%). Granulomas were identified in 29% of biopsy specimens. First-line treatments varied, with corticosteroids (29.6%) and surgery (14.3%) used most frequently. Biologic agents were used in 15.4% of patients, as most studies were published before the biologics era. Four deaths were reported due to postoperative complications. Significant associations were found between the primary site of Crohn’s disease and both esophageal behavior and endoscopic findings. Esophageal Crohn’s disease is a rare entity with diagnostic delays and inconsistent treatment. The variability in clinical features, diagnostic findings, and treatment approaches reported in adult patients, as well as the lack of consensus definitions and standardized management, is reflected in high rates of surgical intervention and morbidity in the past. Improved awareness and collaborative research are needed to establish evidence-based guidelines and improve patient outcomes.
Mela E, Garoufalia Z, Emile SH, Karangeli N, Mantziari S, Tagkalos E, Papanikolaou IS, Papaconstantinou I, Schizas D
Appropriate J-pouch volume associated with improved clinical outcomes and long-term quality of life in patients with ulcerative colitis after ileal pouch-anal anastomosis: results from China UC Pouch Center Union. Intestinal research | 2026-05-07
A well-functioning and well-constructed pouch is crucial for the long-term quality of life (QOL) in ulcerative colitis (UC) patients after ileal pouch-anal anastomosis (IPAA). What pouch volume is appropriate to construct to maintain satisfactory pouch function for better long-term prognosis remains unknown. UC patients who underwent IPAA from January 2008 to January 2024 in our pouch surgery centers affiliated with the China UC Pouch Center Union were enrolled. The primary outcomes were the occurrence of postoperative complications and impaired long-term QOL. A total of 222 eligible UC patients with a median follow-up time of 8.0 years (interquartile range, 4.0-10.3 years) were enrolled. Among the patients, 117 (52.7%) had a pouch with volume <120 mL, whereas 105 (47.3%) had a pouch volume ≥120 mL. We found that patients with pouch volume ≥ 120 mL were more likely to achieve significantly improved long-term QOL (P= 0.013), better bowel function (P= 0.030) as well as have decreased risk of late postoperative complications (P= 0.005), mainly presented as pouchitis (P= 0.039). Furthermore, we demonstrated that a small pouch with volume < 120 mL is an independent risk factor for the development of late postoperative complications (odds ratio, 2.157; P= 0.013) and impaired long-term QOL (odds ratio, 2.049; P= 0.018). A J-pouch volume ≥ 120 mL could be a considerable option for colorectal surgeons in pouch configurations to achieve better long-term prognosis.
Xu W, Dai Z, Ding W, Cui L, Wu X, Zhou W, Ding Z, Du P
Mesenteric preservation vs extended mesenteric excision in Crohn’s disease: A systematic review and meta-analysis.Review The surgeon : journal of the Royal Colleges of Surgeons of Edinburgh and Ireland | 2026-05-06
There remains ongoing debate and lack of consensus regarding the benefit of extended mesenteric excision (EME) compared to limited mesenteric excision (LME) in the surgical management of Crohn’s disease (CD). This study aimed to synthesise the most recent evidence through an up-to-date meta-analysis comparing clinical outcomes following EME versus LME. This study was guided by Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, with prospective registration on PROSPERO (CRD420251020438). PubMed, Cochrane and Scopus were searched for studies published to April 2025. The primary outcome was surgical recurrence, defined as need for repeat surgery for CD. Secondary outcomes included endoscopic recurrence, postoperative complications, length of stay and operative duration. Meta-analysis was performed using RevMan 5.4. Odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs) were calculated. Risk of bias was assessed using ROBINS-I and RoB2 criteria. Six studies (four non-randomized and two randomized), comprising 4469 patients, met inclusion criteria. EME was significantly associated with reduced surgical recurrence compared to LME (OR = 0.31; 95% CI [0.11-0.87]; p = 0.03). There was no difference in endoscopic recurrence between groups (OR 0.77; 95% CI 0.46-1.27; p = 0.30). There were no significant differences in rates of superficial surgical site infection, intra-abdominal collections, anastomotic leaks, operative duration or length of stay. Our findings demonstrate that EME is associated with a significant reduction in surgical recurrence in CD compared to LME, without any increase in post-operative complications, operative time, or length of hospital stay.
O’Mahony A, Cullinane C, Ariaratnam J, Condon E, Fleming CA, Peirce C, Li Y, Coffey JC
Transcriptional and ubiquitinative suppression of macrophage CST3 disrupts colonic homeostasis through defective efferocytosis. Cell death and differentiation | 2026-05-05
To elucidate the role and regulatory mechanisms of macrophage-derived cystatin C (CST3) in Crohn’s disease (CD), focusing on colonic inflammation, macrophage-epithelial interactions, and barrier dysfunction. Colonic samples from CD patients, including inflamed and non-inflamed regions, were subjected to scRNA-seq. In vitro macrophage-epithelial co-culture models and untargeted metabolomics were employed, and the findings were validated using macrophage-specific CST3 knockout (KO) and overexpression mice under TNBS-induced and IL-10 KO colitis conditions. Mechanistic investigations included Co-IP, ChIP-qPCR, ubiquitination assays, rescue experiments, and functional analyses of efferocytosis, macrophage polarization, and barrier integrity. CST3 expression was considerably reduced in macrophages from inflamed CD tissues through suppressor of SMAD5-dependent transcriptional repression and MYCBP2-mediated K48-linked ubiquitination and degradation. Loss of CST3 impaired efferocytosis and M2 polarization by inhibiting the ACVR1C/TGF-β/SMAD pathway. CST3 deficiency also disrupted intestinal epithelial proliferation, compromised barrier function, and increased apoptosis via enhanced NAMPT-INSR signaling and accumulation of the inflammatory cytokines. In mice, macrophage-specific CST3 deletion exacerbated colitis, whereas its overexpression alleviated inflammation and restored epithelial integrity. These findings establish macrophage CST3 as a key regulator of immune-metabolic-epithelial crosstalk in CD, and indicate that restoring CST3 function or targeting its regulatory axis may represent a novel therapeutic strategy for CD.
Wang H, Jiao C, Xing H, Cheng C, Cheng S, Jiang W, Xu Z, Yang J, Sun J, Zhao J
The Impact of Metabolic Bariatric Surgery on Inflammatory Bowel Disease Risk and Outcomes in Adults With Obesity: a Propensity-matched, Nationwide, Analysis. Obesity surgery | 2026-05-05
The risk of de novo inflammatory bowel disease (IBD) after metabolic bariatric surgery (MBS) has been described, but the timing and severity of de novo IBD is unclear. Using MarketScan Databases, patients with severe obesity undergoing Roux-en-Y-gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) were propensity-matched with patients with severe obesity without MBS (controls). Adjusted hazard ratio (aHR) assessed ulcerative colitis (UC) or Crohn’s disease (CD) hazard <3 or ≥3 years from surgery or severe obesity. IBD severity was assessed using healthcare utilization-based proxies including medication exposure, IBD-related hospitalizations, and surgical interventions. The cohort included 100,832 adults with MBS versus 376,855 controls (76.0% females, median age of 44 years). The incidence of IBD was higher in MBS cohort versus controls (61.2 vs. 44.4 per 100,000 adults/year). Within 3 years, patients with MBS had a 24% lower risk of de novo IBD versus controls (aHR: 0.76, 95% CI: 0.60-0.95). When stratified by surgery and IBD type, VSG had reduction in CD risk (aHR=0.46, 95% CI:0.22-0.96), while RYGB had reduction in UC risk (aHR=0.22, 95% CI:0.06-0.75). After 3 years, patients with MBS, particularly VSG, had greater than 2-fold increased risk of IBD (aHR=2.28, 95%CI: 1.02-5.06). Markers of treatment intensity and healthcare utilization did not significantly differ between groups overall; however, a higher proportion of UC patients in the MBS cohort underwent colectomy, though absolute event numbers were small. (8.70% vs 1.57%, p=0.03). While MBS may lower IBD risk initially, IBD risk increases after 3 years, especially UC after VSG, and may be more severe as indicated by the higher proportion of colectomies for patients in the MBS cohort versus controls. Findings regarding treatment intensity should be interpreted cautiously, as objective measures of disease activity were not available in claims data.
Pusateri A, Gokun Y, Allen K, Chang C, Chiplunker A, Butnariu M, Hussan H
Pattern-based histologic approach in colitis without chronic architectural damage: GIPAD recommendations.Review Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver | 2026-05-02
In patients presenting with intestinal symptoms who undergo colonoscopy with mucosal sampling, the pathologist plays a central role in identifying the underlying etiology in order to guide appropriate clinical management. However, common intestinal symptoms such as diarrhea are shared by a broad spectrum of conditions, including infectious diseases, functional disorders (e.g., irritable bowel syndrome), inflammatory bowel disease (IBD), drug-induced injury, and metabolic disorders (e.g., diabetes mellitus). Although serological biomarkers may support the diagnostic workup, they are frequently insufficient to establish a definitive diagnosis. Moreover, endoscopic examination may fail to detect significant mucosal abnormalities even when histology reveals disease-specific patterns, as occurs in lymphocytic and collagenous colitis (i.e., microscopic colitis). In this complex diagnostic landscape, histomorphological evaluation represents a crucial element, allowing integration of microscopic findings with clinical and endoscopic data to reach an accurate interpretation. In recent years, accumulating evidence has demonstrated that similar histological patterns of intestinal injury-such as IBD-like architectural and inflammatory changes or eosinophil-rich infiltrates-may be associated with different underlying etiologies. This overlap is particularly relevant in patients treated with novel oncologic therapies, including tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors (ICIs), and emerging treatments such as chimeric antigen receptor T-cell (CAR-T) therapy. In addition, in daily practice, pathology request forms often lack essential clinical, endoscopic, and laboratory information, further increasing the risk of diagnostic misinterpretation and inappropriate disease attribution. To address these challenges, the Italian Group of Digestive Disease Pathology (GIPAD) proposes a pattern-based histological approach for reporting mucosal damage in patients with colitis. In this first paper, we focus on non-chronic patterns of mucosal injury and discuss their principal differential diagnoses, with the aim of supporting standardized reporting and improving clinicopathological correlation.
Panarese I, Spaggiari P, Albarello L, Arpa G, Gambella A, Grillo F, Vanoli A, Mastracci L, Giordano C, Vasuri F
Venous Thromboembolism After Total Colectomy in Inflammatory Bowel Disease: Risk Factors and Mortality - a Danish Population-Based Cohort Study. Clinical epidemiology | 2026-05-01
Total colectomy is a key intervention in inflammatory bowel disease (IBD) management and a high-risk procedure for postoperative venous thromboembolism (VTE). We investigated risk factors for postoperative VTE and VTE-associated mortality in patients with IBD undergoing total colectomy. We conducted a population-based cohort study using Danish registries (1996-2021), including all patients with IBD who underwent total colectomy (n=5303). We calculated the 90-day cumulative risk of VTE and used Cox regression to assess the association between potential risk factors and VTE. We used the Kaplan-Meier method to calculate 1-year mortality after VTE, and we compared mortality between patients with and without VTE using Cox regression as an estimate of the mortality rate ratio. The 30-day VTE risk was 0.6% in patients with Crohn’s disease and 1.3% in those with ulcerative colitis. During this period, the strongest risk factors were age (adjusted hazard ratio 3.95 [95% CI 1.87-8.37]) for 41-60 years and 2.96 [1.30-6.75] for ≥60 years vs ≤40 years), calendar year of total colectomy (3.84 [1.10-13.34] for 2014-2020 vs 1996-2001), high comorbidity burden (2.14 [0.94-4.88] vs low comorbidity), IBD duration <1 year (1.84 [0.81-4.16] vs 1-5 years), male sex (1.56 ([0.92-2.64]), and corticosteroid use (1.55 [0.86-2.79]). In secondary analyses, comparing preoperative systemic corticosteroid use to non-use, we found a twofold higher 30-day VTE rate. Most associations persisted for 31-90 days, though with some attenuation. The 1-year mortality risk after VTE was 21.0% (hazard ratio of 7.65 [95% CI, 3.12-18.73]). Several patient and clinical factors were associated with elevated postoperative VTE risk, and VTE after total colectomy carried a substantially increased 1-year mortality. These findings may help identify high-risk subgroups and inform future studies of extended thromboprophylaxis and perioperative management in IBD.
Kurt G, Erichsen R
Bayesian prior elicitation on the efficacy of medical therapies in perianal fistulizing Crohn’s disease.★ Journal of Crohn’s & colitis | 2026-05
Robust evidence for most licensed Crohn’s disease therapies is lacking for perianal fistula outcomes due to a lack of dedicated clinical trials. This study aimed to use a Bayesian framework to determine the efficacy of medical therapies for perianal fistulizing Crohn’s disease (PFCD). A formal prior elicitation exercise was conducted by a group of 11 gastroenterologists and 5 statisticians. Consensus priors were developed leveraging both existing published data and clinical expertise, to determine one-year fistula remission rates for medical treatments with 5 different mechanisms of action (anti-TNF, anti-integrin, anti-IL-12/23, anti-IL-23, and JAK inhibitor). Consensus priors on efficacy of each treatment were determined relative to an elicited consensus prior for placebo control. Consensus priors were obtained for the likelihood of fistula remission at 1 year. The prior mean, together with a 90% prior credible interval, of the one-year fistula remission rate was 0.22 (0.05, 0.46) for placebo, 0.58 (0.09, 0.96) for intravenous infliximab, 0.39 (0.06, 0.82) for adalimumab, 0.53 (0.09, 0.93) for subcutaneous infliximab, 0.24 (0.03, 0.60) for intravenous vedolizumab, 0.44 (0.05, 0.90) for upadacitinib, 0.34 (0.04, 0.77) for ustekinumab, and 0.36 (0.04, 0.82) for anti-IL-23 specific agents. Oral upadacitinib and subcutaneous infliximab demonstrated the highest probability for efficacy, alongside intravenous infliximab. We have conducted the first Bayesian prior elicitation exercise in inflammatory bowel disease. The generated priors could be used to enhance the design and analysis of clinical trials in PFCD by improving estimation of treatment efficacy, minimizing sample sizes, and potentially reducing the need for placebo control arms.
Noor NM, Zheng H, Cao Z, Caruso G, Voller C, Cooney R, Din S, Gordon H, Kok KB, Lindsay JO
Quality of Life & PROs (8 papers)
Environmentally relevant concentrations of PFDA exacerbate inflammatory bowel disease through impairing macrophagic efferocytosis of apoptotic intestinal epithelial cells. Ecotoxicology and environmental safety | 2026-05-08
Perfluorodecanoic acid (PFDA), a member of the per- and polyfluoroalkyl substances (PFAS) family, is widely used in industrial and consumer products. The compound is bioaccumulative, raising significant health concerns regarding the pathological consequences of human exposure, which primarily occurs through contaminated drinking water and dietary sources. Previous studies have shown that PFDA exposure has adverse associations with inflammatory bowel disease (IBD). However, the mechanism underlying this association is unclear. This study aims to investigate the impact of PFDA on IBD progression, elucidate the underlying mechanisms, and identify potential therapeutic targets. In this study, we utilized population-based analysis, RNA-sequencing, in vitro and in vivo experiments to elucidate the mechanisms underlying PFDA-induced exacerbation of IBD and explore potential interventions. Our study reveals that PFDA exacerbates IBD progression by inducing macrophage senescence, which impairs efferocytosis of apoptotic intestinal epithelial cells. Notably, metformin counteracts this PFDA-driven pathology. These findings establish the pro-inflammatory mechanism of PFDA and highlight metformin as a potential therapeutic agent, providing new insights for PFAS risk assessment and disease management.
Cui Z, Wang Y, Lu K, Fei X, Zhang J, Liu Z, Ni H, Zhong J, Wan SM, Chen Y
Self-Efficacy Mediates the Dyadic Relationship Between Psychological Distress and Self-Care in Individuals With Inflammatory Bowel Disease and Their Caregivers. The Psychiatric quarterly | 2026-05-07
Emotional distress is common among individuals with inflammatory bowel disease (IBD) and their caregivers, potentially impairing illness management and daily functioning. The psychological mechanisms underlying how depression, anxiety, and stress influence self-care and caregiver contribution to self-care remain unclear in IBD dyads. This study examined the dyadic associations between emotional distress and self-care behaviours in IBD, testing the mediating role of self-efficacy in both patients and caregivers. A multicentre cross-sectional study was conducted in accordance with STROBE guidelines across nine Italian IBD units. Emotional distress was assessed using the Depression Anxiety Stress Scale (DASS-21), self-efficacy using the Self-Care Self-Efficacy Scale (SCSES) for patients and the Caregiver Self-Efficacy in Contributing to Self-Care (CSE-CSC) for caregivers, and self-care behaviours using the Self-Care of Chronic Illness Inventory (SC-CII) and its caregiver version (CC-SC-CII). The Actor-Partner Interdependence Mediation Model (APIMeM) with Bayesian estimation was applied to test direct and indirect effects while adjusting for demographic and clinical covariates. A total of 274 patient-caregiver dyads were enrolled. Patient depression showed credible indirect associations with self-care through lower self-efficacy. Anxiety showed weak and inconsistent associations, with only one credible negative total association between patient anxiety and patient self-care monitoring. Patient stress showed credible positive direct associations with patient self-care outcomes. Caregiver-to-patient partner effects were generally non-credible. Depression undermines self-care in IBD primarily via diminished self-efficacy, whereas patient stress may be linked to adaptive vigilance in patient self-care. Strengthening patient self-efficacy and addressing depressive symptoms may represent relevant targets for supporting self-care in individuals with IBD, while caregiver-focused strategies require further investigation in longitudinal or interventional designs.
Napolitano D, Bozzetti M, Lo Cascio A, Longobucco Y, Magi CE, Iovino P, Vellone E
Caregiver burden in inflammatory bowel disease: a systematic review and meta-analysis. BMC psychology | 2026-05-06
Caregiver burden is increasingly acknowledged in chronic illnesses but its impact in the context of Inflammatory Bowel Disease (IBD) remains underexplored. A systematic review and meta-analysis were conducted following PRISMA 2020 guidelines to evaluate caregiver burden across physical, emotional, psychological, financial, and social domains. Comprehensive database searches were performed in PubMed, Embase, Web of Science and Scopus databases on 3 February 2025. Studies assessing at least one aspect of caregiver burden in IBD were included. Data extraction and bias assessment were carried out independently by reviewers. Pooled prevalence rates for caregiver burden and associated domains were estimated using a random-effects model in R. Out of 383 records, 25 studies met the inclusion criteria, with 12 eligible for meta-analysis. The pooled prevalence of caregiver burden was 470 per 1000 carers (95% CI: 390-560), depression at 370 per 1000, and anxiety at 400 per 1000. Loss of work productivity and activity impairment were reported in 290 and 300 per 1000 caregivers, respectively. Stress, reduced quality of life, and financial burden were also common. Coping strategies varied, with adaptive strategies (e.g., religious practices) linked to lower burden. Caregiver burden was notably higher in cases of active disease, severe IBD, and among caregivers with additional dependents or personal psychiatric histories. This systematic review underscores a substantial and multidimensional burden on caregivers of IBD patients, affecting mental health, productivity and quality of life. Future interventions should incorporate caregiver-centred support mechanisms and resilience training, emphasising psychosocial care as an integral component of IBD management. The study was registered on Open Science Framework (OSF), Registration https://doi.org/10.17605/OSF.IO/YA3NU.
Dadoo N, Prabha PK, Jena A, Birda CL, Raut S, Parajuli S, Sharma A, Medhi B, Sebastian S, Sharma V
Fatigue and mood disorders are highly prevalent in patients with inflammatory bowel disease: A single-centre, cross-sectional study using patient-reported outcomes. Internal medicine journal | 2026-05-06
Fatigue is a common and debilitating symptom in inflammatory bowel disease (IBD), yet it remains under-recognised in clinical practice. This study aimed to quantify fatigue among Australian patients with IBD and examine associations with disease control, psychological distress and quality of life (QoL). We conducted a cross-sectional study of adult patients with IBD at a tertiary centre. Participants completed four validated questionnaires: Functional Assessment of Chronic Illness Therapy-Fatigue, IBD-Control 8, Short Inflammatory Bowel Disease Questionnaire and Hospital Anxiety and Depression Scale. Associations between fatigue and other patient-reported outcomes were analysed, and multivariate regression identified independent predictors of fatigue. Of 1179 patients invited, 327 (28%) participated; 166 (51%) had Crohn disease, 152 (46%) ulcerative colitis and nine (3%) IBD-unclassified. Severe fatigue was reported in 46% of participants. Depression and anxiety were present in 29% and 41% of patients respectively. Fatigue was significantly associated with poorer disease control and QoL (P < 0.0001). On multivariate analysis, independent predictors of fatigue included depressive symptoms (β = -1.03, P < 0.0001), anxiety (β = -0.41, P = 0.003), reduced disease control (β = 0.70, P < 0.0001) and lower QoL (β = 0.23, P = 0.0006). Notably, in a subgroup of 55 patients (17%) with well-controlled disease, fatigue remained strongly linked with psychological distress and impaired QoL. Fatigue is highly prevalent in IBD and persists even among patients with good disease control. Psychological distress, poor disease control and reduced QoL are independently associated with fatigue, underscoring the need for routine screening and multidisciplinary management.
Chen A, Wong D
The role of DAP12 in immune-related inflammatory diseases.Review Inflammation research : official journal of the European Histamine Research Society … [et al.] | 2026-05-06
DNAX-activated protein 12 (DAP12) is a key transmembrane adaptor protein containing an immunoreceptor tyrosine-based activation motif. DAP12 associates with a broad spectrum of cell surface receptors, including triggering receptors expressed on myeloid cells (TREM1 and TREM2), myeloid DAP12-associating lectin-1 (MDL-1), sialic acid-binding immunoglobulin-like lectin 15 (Siglec15), killer cell immunoglobulin-like receptor (KIR), NKG2C/CD94, and NKp44. They form a sophisticated signaling network that precisely regulates cellular activation, differentiation, and the balance between pro-inflammatory and anti-inflammatory responses. DAP12 is predominantly expressed in innate immune cells, including monocytes/macrophages, microglia, osteoclasts, and natural killer (NK) cells, where it governs key processes like cytokine production, cytoskeletal remodeling, and cytotoxic activity. Dysregulation of DAP12 signaling has been implicated in the pathogenesis of multiple immune-related inflammatory diseases, such as multiple sclerosis, Alzheimer’s disease, rheumatoid arthritis, inflammatory bowel disease, and systemic lupus erythematosus. In these conditions, DAP12 contributes to either protective or pathological outcomes depending on the receptor complex and microenvironment. This review provides a comprehensive overview of the structural characteristics of DAP12, its interaction with relevant receptors, and its specific functions in various cell types and immune-mediated inflammation.
Lu J, Shi L, Jin G, Yang Y, Zhu F, Zhou G
Specific Depressive Symptoms are Associated with Subtypes of Fatigue in Inflammatory Bowel Disease. Journal of clinical psychology in medical settings | 2026-05-05
Fatigue is common in inflammatory bowel disease (IBD) yet firm understanding of its management remains unclear. While psychosocial factors influence fatigue, less is known about how these factors differ among fatigue subtypes. This study examined the contributions of self-reported disease activity and psychosocial factors to five fatigue subtypes. Patients with Crohn’s disease or ulcerative colitis were recruited from an academic medical center. Participants completed online surveys including the Multidimensional Fatigue Inventory (MFI-20) and measures of depression, anxiety, pain interference, pain catastrophizing, and insomnia. In 312 participants, depression was most associated with subtypes of fatigue. Percent variance attributable to fatigue subtypes: general (17%), physical (12%), mental (25%), and reduced motivation (17%). Anxiety was most strongly associated with activity avoidance (17% variance). Factors associated to a lesser degree were pain interference and insomnia. The contribution of psychosocial factors to fatigue was as, if not more substantial than patient-reported disease activity. Symptom-level analysis found cognitive and behavioral symptoms of depression to be most associated with fatigue. While subtypes of fatigue differ in their association to psychosocial factors, depression was a consistent and strongly associated factor. Results highlight the importance of screening for depression and point to specific treatments that may be beneficial for fatigue management.
Duarte B, Said H, Salwen-Deremer J
Digital health technologies for monitoring and managing IBD-related fatigue: A scoping review.Review Digital health | 2026-04-28
Fatigue is a common, persistent symptom in inflammatory bowel disease (IBD). Digital health technologies (DHTs) may enable ongoing monitoring and timely support, yet the relevant evidence remains dispersed. To map how DHTs are used to monitor or manage IBD-related fatigue, summarize intervention characteristics, measures, feasibility, acceptability, and reported effectiveness. Following the Joanna Briggs Institute (JBI) methodology and the Arksey O’ Malley framework, and reported per PRISMA extension for Scoping Reviews (PRISMA-ScR), eight databases and gray sources from inception to 30 October 2025 were searched using a Population-Concept-Context schema. Eligible studies used a DHT to assess or manage IBD-related fatigue. Screening and data charting were conducted in duplicate; findings were synthesized narratively. Eleven studies were included: four randomized trials, two cohorts, one program evaluation, one non-randomized feasibility study, one multisensor pilot, one mixed-methods study, and one qualitative study. Technologies fell into six groups: telemedicine portals, web-based cognitive behavioral therapy (CBT) self-management, mobile self-management applications, device-linked neuromodulation, wearable-enabled monitoring, and eDiary-based symptom tracking. Feasibility and acceptability were commonly reported in patient-facing studies, and implementation-focused evidence suggested professional acceptability when roles and workflows were clearly defined. Randomized comparisons rarely showed significant differences in fatigue improvement between the groups. Patient-reported outcomes predominated, including IBD-F, FACIT-F, FSS, and PROMIS-Fatigue. Device metrics were mainly activity-based with limited higher-frequency physiology. Engagement often declined, and misalignment between measurement and intervention design was common. Current evidence suggests that DHTs for IBD-related fatigue are generally feasible and acceptable in the studied contexts, but evidence for reducing fatigue is limited and mixed. A pragmatic next step may be a hybrid measurement strategy combining validated fatigue questionnaires, brief daily ratings, and a small set of interpretable device metrics within timing-sensitive trial designs to support implementation in routine care.
Zhu T, Sheng G, Zhou X, Yang L
Scutellaria baicalensis-Derived Extracellular Vesicles Alleviate Inflammatory Bowel Disease by Inhibiting the NF-κB/NLRP3 Pathway. International journal of nanomedicine | 2026-04-27
Plant-derived extracellular vesicles (PDEV) are emerging as natural nanomedicines for various diseases. Scutellaria baicalensis (S. baicalensis) is a traditional Chinese herb long used to treat intestinal inflammatory bowel disorders (IBD), with its therapeutic effects attributed to bioactive flavonoids such as baicalin and wogonin. However, whether SEV contribute to its anti-inflammatory activity remains unexplored. The assembled multi-component nature of SEV, which carry flavonoids, lipids, proteins, and miRNAs, suggests a potential to exert therapeutic effects against IBD through mechanisms distinct from isolated compounds, with potential advantages in bioavailability and multi-target engagement. We demonstrated that SEV exert potent antioxidant and anti-inflammatory effects in LPS-stimulated RAW264.7 macrophages and Caco-2 intestinal epithelial cells. Moreover, we assessed the therapeutic effects of SEV on dextran sulfate sodium (DSS)-induced IBD in a murine model. In inflamed RAW264.7, SEV modulated the NF-κB/NLRP3 signaling axis to exert anti-inflammatory effects. They scavenged reactive oxygen species (ROS), restored mitochondrial membrane potential, upregulated the anti-inflammatory cytokine IL-10, and suppressed the pro-inflammatory cytokines TNF-α, IL-6, and IL-1β. In Caco-2 intestinal epithelial cells, SEV also repaired intestinal barrier function by restoring expression of the tight junction proteins Zonula Occludens-1 (ZO-1), Claudin-1, and Occludin (OCLN), alongside reduced TNF-α levels. In vivo, SEV accumulated at colonic inflammatory loci to effectively alleviate IBD, as evidenced by improved body weight and increased colon length. This protective effect was mediated through inhibition of the NF-κB/NLRP3 signaling axis in colon tissues, which subsequently restored intestinal barrier integrity by increasing goblet cell numbers, upregulating OCLN proteins, and enhancing Mucin2 (MUC2) secretion, while simultaneously rebalancing inflammatory cytokines through suppression of TNF-α/IL-1β and promotion of IL-10 production. SEV have the potential to protect the colon against DSS-induced colitis by inhibiting the NF-κB/NLRP3 signaling pathway, providing a promising therapeutic candidate for IBD.
Miao R, Wang S, Yin H, Zhu R, Yin Y, Liao W, Wang S, Zhang J, Li R, Xu J
Epidemiology & Outcomes (7 papers)
Association of frail status with incident digestive diseases: A large prospective cohort study. Digestive diseases (Basel, Switzerland) | 2026-05-07
Frailty, reflecting age-related decline in physiological reserve, has been implicated in adverse health outcomes, but its contribution to digestive disease risk is not well established. Leveraging two prospective cohorts from the UK Biobank (n≈340,000 and n≈358,000) with participants free of gastrointestinal or hepatobiliary-pancreatic conditions at baseline, we evaluated incident disease over a median follow-up of 13.7 years using a validated frailty phenotype. Individuals classified as frail showed consistently higher rates of digestive disorders than robust peers. After multivariable adjustment, hazard ratios (HRs) for frailty were 1.65 (95% CI 1.57-1.72) for overall gastrointestinal disease and 1.78 (1.66-1.92) for hepatobiliary-pancreatic disease. Risk elevations were observed for gastroesophageal reflux disease (HR 1.70), peptic ulcer (1.81), inflammatory bowel disease (1.48), irritable bowel syndrome (2.43), diverticulosis (1.38), constipation (2.25), coeliac disease (1.58), cirrhosis (2.22), metabolic dysfunction-associated steatotic liver disease (1.76), gallbladder disease (1.69), and pancreatic disease (1.60), all with P values <0.01. Subgroup analyses across age, sex, adiposity, and comorbidity strata yielded similar results. Exploratory mediation using the C-reactive protein-to-albumin ratio, an index of inflammation and nutritional status, suggested partial attenuation of the frailty-disease associations (up to 9.5% for inflammatory bowel disease and 4.1% for cirrhosis). Excluding early events and adding extensive lifestyle and biochemical covariates did not materially change the findings. Frailty, including pre-frail states, appears to be an independent marker of vulnerability to a broad range of digestive diseases, supporting its potential use in early risk assessment and targeted preventive strategies.
Qin Z, Shi L, Zhang K, Pan M, Liu Y, Peng J, Zhang Y, Zhang Z, Zhang S, Wei H
The trend of obesity and inflammatory bowel disease in Australia and New Zealand: a bi-nation cohort study. Internal medicine journal | 2026-05-05
The paradigm of inflammatory bowel disease is shifting from a malabsorptive, undernourished state to one where obesity is a prevalent comorbidity, yet large-scale Australasian data are lacking. We conducted a retrospective, multicentre cohort study from the binational Crohns Colitis Care registry, highlighting a high prevalence of obesity and overweight in our cohort where increasing body mass index was associated with older age and cardiometabolic comorbidities including diabetes and metabolic dysfunction associated steatotic liver disease.
Kaazan P, Seow W, Wilson B, Connor SJ, Andrews JM
Outcomes of Root Canal Treatment in Patients With Autoimmune Disease: A Retrospective Case-Control Study. International endodontic journal | 2026-05-04
The purpose of this study was to compare the outcome of nonsurgical root canal treatment (RCT) in patients with autoimmune diseases (AD) with the outcome in patients without AD. The null hypothesis was: there is no difference in the outcomes of RCT regardless of the patient group. Results were also compared among AD subgroups: inflammatory bowel disease (IBD), rheumatoid arthritis (RA), and psoriasis (Ps). Data were obtained from a database using codes corresponding to the National Health Insurance Dental Fee Schedule. Patients diagnosed with AD who received primary RCT at the Veterans Health Service Medical Center from 2010 to 2022 formed the study group. Controls were matched using propensity score matching for age, sex, arch type, and tooth type. Preoperative periapical lesions, canal filling quality, and RCT outcomes were assessed through radiographs, including panoramic, periapical, and cone-beam computed tomography images. Outcomes were evaluated at approximately 1 year and at maximum follow-up. Chi-square tests and logistic regression were used to evaluate associations between AD and RCT success. The study included 203 ad patients (317 teeth) and 203 controls (312 teeth). At 1 year, success rates were 69.4% in AD patients and 73.7% in controls (p = 0.268). Within the AD group, success rates were 64.6% for IBD, 75.3% for RA, and 73.2% for Ps. Patients with IBD showed only statistical significance (p = 0.025). The mean observation duration for the maximum follow-up was approximately 50 months. Long-term success rates were 61.5% for AD and 66.0% for controls (p = 0.207). Multivariate logistic regression analysis indicated that arch type, tooth type, and the presence of preoperative apical lesions were significant factors influencing the outcome of RCT. Comparing the 1-year and long-term outcomes, IBD, RA, and Ps showed a similar trend of decreased success rates, although the differences were not statistically significant. RCT success rates in patients with AD were comparable to those of controls. Multivariable analysis revealed that clinical factors were the primary predictors of success, rather than the presence of AD. Therefore, high-quality clinical procedures are the critical factor for favorable outcomes in AD patients.
Lee S, Kim E, Jung H, Kim H, Kim S
Safety of IL-17A Inhibitors in Patients With Moderate to Severe Psoriasis in a US Claims Data-Based Cohort Study. Journal of psoriasis and psoriatic arthritis | 2026-05-02
Safety outcomes from IL-17A inhibitors have not been fully evaluated. Compare the risk of seven safety outcomes in patients with psoriasis who started treatment with either ixekizumab or secukinumab vs other biologics to treat psoriasis. In this cohort study (Apr 2016 - Dec 2022), we used US claims data to assess the risk of infections, major adverse cardiac events (MACE), inflammatory bowel disease (IBD), malignancy, and anaphylaxis, in patients with psoriasis starting an IL-17A inhibitor vs other biologics (TNF, IL-12/23, or IL-23 inhibitors). Among 4261 IL-17A inhibitors users we observed no meaningfully increased risk of MACE (RR = 0.67, 0.27-1.63), or malignancy (RR = 0.92, 0.58-1.45) vs patients initiating other biologics. After propensity score matching IL-17A inhibitors users had a 3-fold increase in the risk of oral candidiasis (RR = 3.43; 1.48-7.84), a 19% increase in the risk of outpatient infections (RR = 1.19; 1.05-1.35) and a 40% increased risk of serious infections with wide confidence intervals (RR = 1.40; 0.72-2.71). We observed a signal for an increased risk of IBD based on very few events. Patients with psoriasis using an IL-17A inhibitor had an increased risk of oral candidiasis and outpatient infections but no increase for MACE, anaphylaxis, or malignancy compared to other biologics.
Schneeweiss MC, Merola JF, Jin Y, Wyss R, Anand P, Mostaghimi A, Schneeweiss S, Glynn RJ
Pharmacological interventions for obesity in patients with inflammatory bowel disease: A systematic review of GLP-1 receptor agonist efficacy and safety.Review Obesity pillars | 2026-04-28
Obesity is an escalating global health challenge, particularly among patients with inflammatory bowel disease (IBD), where the coexistence of metabolic dysfunction and chronic intestinal inflammation complicates clinical management. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are potent weight-management agents; however, their efficacy and safety profiles in patients with obesity and IBD specifically regarding gastrointestinal tolerability remain poorly characterized. We conducted a systematic review to evaluate the impact of GLP-1 RAs on anthropometric outcomes in patients with obesity and IBD. A comprehensive search of PubMed, Embase, and Web of Science was performed through November 10, 2024. Observational studies reporting weight-related metrics were synthesized. To ensure scientific rigor, all imperial units were converted to metric (kg), and a narrative synthesis was employed to address heterogeneity in study designs. A total of n = 7 studies (sample sizes from 16 to 47,424 participants) were analyzed. GLP-1 RAs consistently demonstrated significant weight reduction, with reported losses ranging from a median of -6.2 kg (range: -3.4 to -8.5 kg) to a mean of approximately -9.5 kg (SD = 8.5) over follow-up periods of 3-18 months. Greater weight loss was observed in patients with higher baseline body mass index and longer treatment duration. Overall, reductions ranged from approximately -16 lbs (SD = 13) to -26 lbs (SD = 20), with longer follow-up studies (up to 450 days) showing median reductions of -8.15 kg (range: -15.9 to -2.2 kg). GLP-1 RAs are effective pharmacological adjuncts for weight loss in patients with obesity and IBD, with outcomes modulated by treatment duration and agent selection. These findings support the clinical utility of incretin-based therapies in this complex patient population. However, large-scale randomized controlled trials are essential to establish long-term safety and determine the impact of these agents on IBD disease activity.
Jan A, Dubwa D
Associations of prenatal exposure to maternal autoimmune disorders with a wide spectrum of psychiatric and neurodevelopmental disorders in offspring-a nationwide cohort study. Human reproduction open | 2026-04-26
Are children exposed in utero to various maternal autoimmune disorders (ADs) and autoinflammatory disorders (AIDs) at greater risk for developing any of a wide range of psychiatric or neurodevelopmental disorders? Prenatal exposure to maternal ADs and AIDs, but for those of the nervous system, was at modest effect sizes associated with a number of primarily early onset neurodevelopmental disorders. Prenatal exposure to maternal immune activation and certain ADs or AIDs has been associated with psychiatric and neurodevelopmental disorders in offspring. However, most studies examined only one specific maternal exposure, such as rheumatoid arthritis, in relation to one specific outcome, such as autism spectrum disorder (ASD). The potential impact of a broader range of maternal AD/AIDs on various mental outcomes remains largely unexplored. A nationwide, population-based cohort study of all live births in Finland from 1996 to 2014, with follow-up to 2021 (N = 1 107 802). Analyses were conducted from October 2023 to December 2025. Maternal diagnoses of AD/AIDs, recorded prior to and/or during pregnancy, were identified through Finnish National Health Registers (N = 34 033). Cox regression was used to estimate the hazard ratios (HRs) with 99% and 95% CIs of psychiatric and neurodevelopmental disorder diagnoses in offspring to AD/AIDs mothers. Of the 1 107 802 births, 3.2% were to mothers with an AD/AID. Offspring exposed to maternal AD/AIDs had a 15% higher risk of a major psychiatric disorder (HR, 1.15 [99% CI, 1.09-1.21]) and an 18% higher risk of a neurodevelopmental disorder (HR, 1.18 [99% CI, 1.14-1.22]).Combining AD/AIDs according to the main body system affected, associations with offspring’s mental diagnoses were detected mainly for connective tissue AD/AIDs and endocrine AD/AIDs. Although most effect sizes were modest (HRs below 2), there were two notable exceptions with more than 2-fold risk: (i) ASD in autoimmune thyroiditis, and (ii) other behavioral or emotional disorders (F98) in pernicious anemia. A 70-99% higher risk for certain neurodevelopmental disorders or milder regulatory disturbances was observed in offspring exposed to systemic vasculitis, type 1 diabetes mellitus (T1DM), acute thyroiditis, Crohn’s disease, and SIC (being polymyalgia rheumatica, Sjögren’s syndrome, and hypermobility syndrome). The T1DM associations were not completely mediated by adverse birth factors. The number of exposure-discordant siblings was insufficient to fully adjust for shared unmeasured familial confounding, and paternal information and breastfeeding data were unavailable. Second, some AD/AIDs were rare, limiting the statistical power. The numbers of exposed cases with outcome in the two associations with largest effect size was limited (n = 9 and 20). Third, rare prodromal AD/AID symptoms cannot be excluded, potentially causing misclassification. Fourth, some AD/AIDs recorded prior to pregnancy might have resolved before pregnancy, unknown to the study. Fifth, grouping AD/AIDs by the main affected body system implies a risk for not detecting true associations of individual AD/AIDs. Finally, the study is exploratory, and the observational design prevents causal inference. The findings may provide information for maternity care and family planning clinics potentially alleviating concerns among mothers with an AD/AID regarding offspring risk of neurodevelopmental and psychiatric disorder. This research was funded by Prima Child and Adult Psychiatry Stockholm AB (E.S.), the Swedish Research Council, Sweden (C.L., 2022-01188), the Swedish Brain Foundation, Sweden (C.L., FO2024-0194 and FO2025-0276-HK-192), Bo and Ulla Lundevall, Ulf Lundahl Memorial Fund, the regional agreement on medical training and clinical research (ALF) between Region Stockholm and Karolinska Institutet, Sweden (C.L., RS2021-0855 and 2023-0859) and China Scholarship Council (W.C.). The authors have no conflict to declare. N/A.
Skott E, Cai W, Stiernborg M, Fogdell-Hahn A, Giacobini M, Gissler M, Nivins S, Lavebratt C
Analgesic Use in Patients with Mild Inflammatory Bowel Disease-A Nationwide Cohort Study Based on Prescription Data. Journal of clinical medicine | 2026-04-20
Background: In patients with Crohn’s disease (CD) and ulcerative colitis (UC) disease severity and activity have been associated with pain. Data on analgesic use in patients with mild disease, however, are limited. We examined prescribed analgesics in mild CD and UC. Methods: In this cohort study, based on nationwide Danish prescription data, we identified incident patients (1996 through 2020) with mild CD (N = 5348) and UC (N = 15,622). Mild disease was defined by absence of advanced medical treatments, and no surgeries, in the period of 3.5 years after the diagnosis. We examined opioids, nonsteroidal anti-inflammatory drugs (NSAIDs), and paracetamol. We also examined opioid use in CD compared to UC. Results: In mild CD, the proportions of patients using analgesics in 2001 and 2020 were: strong/weak opioids 9.1% and 10.0%, chronic opioids 3.2% and 4.1%, NSAIDs 12.4% and 8.5%, and paracetamol 4.0% and 21.7%, respectively. In mild UC, the corresponding proportions in 2001 and 2020 were: strong/weak opioids 6.2% and 7.2%, chronic opioids 2.9% and 2.7%, NSAIDs 12.7% and 8.3%, and paracetamol 2.4% and 19.5%, respectively. The adjusted OR for chronic opioid use in mild CD relative to mild UC was 1.61 (95% CI 1.41-1.85). Conclusions: We found a widespread use of prescribed analgesics in patients with mild IBD. The trends across two decades were similar for both diseases: a steep increase in paracetamol, a modest decline in NSAIDs, a slight decline in weak opioids, but no decline in strong opioids. The risk of chronic opioid use was higher in mild CD than in mild UC. We suggest that patients with mild disease may have pain issues that need to be managed clinically.
Nørgård BM, Thorarinsson CT, Zeiss KE, Dalal RS, Andersen ML, Lund K, Friedman S, Kjeldsen J, Knudsen T
Pediatric IBD (6 papers)
“Being a light at the end of the tunnel”: Peer mentor experiences on supporting adolescents with inflammatory bowel disease. Journal of pediatric psychology | 2026-05-06
Inflammatory bowel disease (IBD) is a stigmatized and impairing chronic disease frequently diagnosed during adolescence. Adolescents with IBD may benefit greatly from psychosocial support, with early literature indicating effectiveness of formal mentorship programs for mentee-related outcomes. However, limited research has examined the mentor experience within IBD populations. The present study qualitatively examined the perspectives of young adult mentors participating in a peer mentorship program for adolescents with IBD. Young adults with IBD participated as mentors in the virtual iPeer2Peer © mentorship program across three tertiary pediatric centers. Twelve mentors participated in the present study through two focus groups. Interviews were analyzed following reflexive thematic analysis. Three themes were developed: (1) program delivery, (2) perceived value of participating in the program, and (3) membership dynamics. Mentors discussed logistical aspects of program implementation, including training needs, challenges in working with adolescent mentees, and factors shaping the in-call experience. The personal value of mentoring others was underscored, including growth within mentors’ own IBD journey, enhanced interpersonal qualities, and perceptions of making a difference. Finally, mentors highlighted the importance of a strong mentorship relationship and factors which supported growth over time. Present results underscore the benefit of peer mentorship in IBD, highlight the importance of incorporating lived experience in patient care, and provide important avenues for improvement of mentorship programs within the healthcare context. Further research is needed to continue to advance understanding of peer mentorship in IBD and its implementation within clinical care.
Ford MK, Jones K, Simourd LE, Stinson JN, Ahola Kohut S
Association between coronavirus disease 2019 and new-onset autoimmune diseases during the early phase of the pandemic. PloS one | 2026-05-05
Emerging evidence suggests that viral infections, including SARS-CoV-2, may trigger autoimmunity. This study investigated the risk of developing autoimmune diseases following coronavirus disease 2019 (COVID-19) using sequence symmetry analysis. We utilized nationwide population-based data from South Korea by linking the National Health Insurance Service database with the Korea Centers for Disease Control and Prevention Agency COVID-19 registry. This study included 2,678 patients with COVID-19 and 92,725 patients without COVID-19 identified between 01/10/2020 and 30/06/2021, during the early phase of the pandemic. Both groups consisted of individuals who were diagnosed with autoimmune diseases within 180 days before or after the index date. We calculated the adjusted sequence ratio (aSR) to compare the incidence of autoimmune diseases within 180 days before and from 14 to 180 days after the index date (the COVID-19 diagnosis date for the COVID-19 group and the first medical visit for the non-COVID-19 group). The differences in autoimmune disease incidence between the groups were evaluated using the ratio of aSR (RaSR). The incidence of newly diagnosed autoimmune diseases-Behcet’s disease (RaSR, 2.03), ankylosing spondylitis (2.04), ulcerative colitis (1.15), Crohn’s disease (2.22), psoriasis (1.27), type 1 diabetes mellitus (1.61), and Graves’ disease (1.14)-was significantly higher in the COVID-19 group than in the non-COVID-19 group after the index date. Subgroup analysis comparing patients with non-severe COVID-19 with those without COVID-19 yielded consistent findings. Furthermore, the incidence of inflammatory bowel diseases was higher in the non-severe COVID-19 group after the index date (RaSR, 1.29). These findings reinforce growing evidence that COVID-19 could induce autoimmunity and increase the risk of developing autoimmune diseases. Therefore, clinicians should remain vigilant for potential autoimmune complications in patients with a history of COVID-19 when clinically indicated.
Park JH, Lee MT, Jung SY, Choi ST, Choi SH
The evaluation of motor deficits in children with ulcerative colitis: a cross-sectional study. European journal of pediatrics | 2026-05-04
While the gastrointestinal symptoms of ulcerative colitis (UC) are well-defined, its impact on motor development in children remains poorly understood. We aimed to assess motor proficiency, handgrip strength, and physical activity levels in children with UC and to investigate associations with disease activity. In this cross-sectional study, 49 children with UC aged 8-17 years and 41 age‑ and sex-matched healthy controls were enrolled. Disease activity was assessed using the Pediatric Ulcerative Colitis Activity Index, and laboratory markers including C-reactive protein and erythrocyte sedimentation rate were measured. Motor proficiency was evaluated using the Bruininks-Oseretsky Test of Motor Proficiency, Second Edition. Handgrip strength was measured with a dynamometer, and physical activity was assessed via the Physical Activity Questionnaire (PAQ). Group comparisons were adjusted for age, sex, socioeconomic status, and body mass index, with False Discovery Rate correction for multiple testing. Children with UC scored significantly lower on the Total Motor Composite than controls (37.4 vs. 45.1, p < 0.001). Adjusted analyses revealed a specific pattern: fine motor skills were preserved, but significant deficits were found in gross motor domains, including bilateral coordination and strength and agility (all p < 0.001). Handgrip strength differences lost significance after adjustment for body mass index, and no difference was observed in physical activity. Within the UC group, a higher erythrocyte sedimentation rate correlated with lower non-dominant handgrip strength (ρ = - 0.533, p < 0.001) and poorer agility (ρ = - 0.414, p = 0.003). Children with UC exhibit significant gross motor deficits, even during clinical remission. These cross-sectional findings indicate that clinically well children may still have impaired motor proficiency compared to healthy peers. However, longitudinal studies are needed to determine whether these deficits predate diagnosis, emerge during active disease, or persist despite remission. • The primary treatment goal in ulcerative colitis with children is the resolution of symptoms and intestinal inflammation. • The potential effects of ulcerative colitis on a child’s motor function are not routinely assessed in clinical practice. • Children with ulcerative colitis have significantly lower overall motor proficiency scores compared to their healthy peers. • Children in clinical remission may still have impaired motor skills, indicating a potential need for comprehensive functional assessment during follow-up.
Akbulut UE, Atalay A, Isik İA, Sivil N, Sarı M, Birsen G, Kara OK, Kara K, Ulu HS, İnal HA
“She just wants to be a normal kid”: Adolescents with inflammatory bowel disease and their caregivers’ transition from paediatric to adult care. British journal of health psychology | 2026-05
Adolescents with inflammatory bowel disease (IBD) experience disruptions to normal adolescent development. Lack of preparation for transition from paediatric to adult care can have negative biopsychosocial outcomes. We aimed to explore adolescents’ perspectives on how IBD affects their lives. Additionally, we aimed to understand adolescents and their parents’ views on transition from paediatric to adult IBD care. Qualitative study. Adolescents and parents participated in semi-structured interviews together. Participants included eight adolescents with IBD (four females; four with Crohn’s disease, two with ulcerative colitis and two with IBD-U; mean age = 16) and their parent(s) (n = 9). Data were analyzed using template thematic analysis. Three themes were identified that reflected how IBD conflicts with typical adolescent development because of the need for careful planning to manage the disease and its symptoms (e.g., loss of bowel control, fatigue). They also described the active role parents currently play in managing their child’s IBD, from managing medication to organizing appointments and communicating with healthcare professionals. Anxiety and apprehension of adolescent participants towards transitioning from adolescent to adult care were also captured. Healthcare providers and carers must work together with adolescents with IBD to ensure they are ready for adult care, where they will need to take sole responsibility for managing their chronic condition.
de Gooyer M, Mackay MI, Mikocka-Walus A, Biurra YC, Emerson C, Klas A, Raven L, Massuger W, Giles EM, Evans S
The Current Use and Future Perspectives of Biosimilars in Pediatric Healthcare: A Narrative Review. Health science reports | 2026-04-30
The integration of biosimilars into pediatric healthcare represents a significant evolution in treatment accessibility and cost-effectiveness. Biosimilars-biological products highly similar to already approved biologics, have emerged as promising alternatives for managing chronic and rare pediatric conditions, including inflammatory bowel disease, juvenile idiopathic arthritis, psoriasis, asthma, lupus nephritis, and growth hormone deficiencies. Despite regulatory, clinical, and societal challenges, current data suggest biosimilars demonstrate comparable safety, efficacy, and immunogenicity profiles to their originator products. The review consolidates findings from recent clinical trials, real-world data, and regulatory landscapes across the US and EU, emphasizing the growing role of biosimilars in pediatric pharmacotherapy. It also explores future directions in biosimilar development, highlighting the need for improved pediatric-specific research, regulatory harmonization, and stakeholder education to ensure wider adoption and optimized outcomes in children. A structured literature search of PubMed, Scopus, Web of Science, and Google Scholar (2003-March 2026) identified English-language studies on pediatric biosimilars. Relevant clinical, regulatory, and review articles were thematically synthesized. In pediatric patients with chronic conditions such as inflammatory bowel disease and rheumatologic disorders, biosimilars like infliximab and adalimumab offer efficacy and safety comparable to originator biologics, while lowering treatment costs. Economic analyses demonstrate that biosimilars are typically 15%-45% cheaper than reference products in Europe, and in some markets up to 85% lower, improving affordability and access to treatment in pediatric populations. Biosimilars have a great deal of promise to improve therapeutic access and lower medical expenses associated with pediatric care. However, to maximize results and guarantee therapeutic fairness in pediatric medicine, broader adoption necessitates increased age-specific clinical trials, harmonized regulations, better training for healthcare providers, and increased stakeholder trust.
Ahmed Z, Maha TT, Nowsher S, Taslim W, Fatema-Tuz-Zohora, Sharmin S, Yasmin H
Long-Term Outcomes of Mediterranean-Adapted Crohn’s Disease Exclusion Diet in Mild Pediatric Crohn’s Disease: A Real-Life Study from a Referral IBD Center. Nutrients | 2026-04-20
Background: Exclusive enteral nutrition (EEN) is the recommended first-line therapy for induction of remission in pediatric mild-to-moderate Crohn’s disease (CD), but its restrictive nature often limits adherence and long-term sustainability. A modified version of the Crohn’s Disease Exclusion Diet (CDED), integrating Mediterranean dietary principles, was developed to offer a more acceptable alternative while preserving therapeutic efficacy. Methods: We conducted a retrospective, single-center study comparing short- and long-term outcomes of a Mediterranean-adapted CDED (M-CDED) with partial enteral nutrition (PEN) versus standard EEN in children with mild-to-moderate CD. Clinical remission was assessed after 8 and 16 weeks, while long-term outcomes were assessed after 1 and 2 years. Results: Data collected from thirty-two patients were analyzed (EEN, 14; M-CDED, 18). Clinical remission rates were comparable after 8 weeks (92.8% EEN vs. 94.4% M-CDED) and 16 weeks (100% in both groups). However, at 12 and 24 months, M-CDED was associated with significantly higher rates of clinical and biochemical remission and a markedly lower need for biologic drugs (12-month biologic initiation: 50% EEN vs. 11.1% M-CDED; p = 0.01). Adherence to M-CDED was excellent throughout follow-up. Conclusions: M-CDED with PEN appears to be as effective as EEN for remission induction, with improved long-term disease control and reduced therapeutic escalation. These findings support the feasibility of M-CDED as a sustainable option for long-term management of pediatric CD. Prospective studies are needed to confirm these results.
Alvisi P, Valerii MC, Perre E, Barbieri G, Rizzello F, Congiu M, Pranzetti A, Dussias NK, Sbravati F, Imbesi V
AI & Machine Learning (5 papers)
Development and Clinical Validation of an Automated Artificial Intelligence System for Bowel Wall Thickness Assessment in Adult Inflammatory Bowel Diseases. Ultraschall in der Medizin (Stuttgart, Germany : 1980) | 2026-05-07
Intestinal ultrasound (IUS) is used to assess and monitor inflammatory bowel disease (IBD). Bowel wall thickness (BWT) is its key marker, but accurate measurement is operator-dependent and requires expertise. Artificial intelligence (AI) may reduce variability and support IUS implementation. We developed and validated an AI model to detect bowel wall layers and measure BWT. We developed a deep learning system (BowelAssist,BA) based on pre-trained convolutional neural network. A dataset of 9000 images (711 patients, 421 IBD) was used for training (80%), validation (10%) and testing (10%). Ground-truth annotations of bowel wall layers for 3000 segments were provided by an expert sonographer. External validation was performed live in 35 patients (67 bowel segments), with additional blinded evaluation by a trained operator in 19 (30 segments). BA performance -including BWT measurement, wall-layer recognition, and intra- and inter-observer agreement- was compared with manual measurements using Pearson’s correlation and Bland-Altman analysis. BA analysis was feasible in 94.7% of measurements. It showed excellent agreement with manual BWT measurements (r=0.88 for cross-sectional and r=0.77 for longitudinal scans), and low mean absolute errors (<0.45mm). Sensitivity and specificity for detecting pathological BWT were 83.6% and 95.7%. Intra-observer reproducibility of BA measurements was >0.90 and inter-observer reproducibility between expert and trained operators was 0.53 for cross-sectional and 0.57 for longitudinal scans. Stratification recognition showed sensitivity of 90.1% and specificity of 83.8%. AI-based model provides accurate, reproducible assessment of BWT supporting its integration into clinical and research workflows for objective evaluation of IBD activity.
Maconi G, Cassella DG, Natalello G, Marra A, Cataletti G, Anand PK
Multi-omics-based machine learning model predicts response and guides treatment in Crohn disease: a case study in nutritional therapy.★ Inflammatory bowel diseases | 2026-05-04
Biomarkers are needed to predict treatment response and guide therapeutic decisions in Crohn disease (CD). We aimed to develop and validate a multi-omics machine learning (ML) model to predict response to nutritional therapy in pediatric CD. Treatment-naive children with newly diagnosed CD who were initiating exclusive enteral nutrition (EEN) were prospectively enrolled in this study. Metabolomics and lipidomics were measured in the serum and stool, as well as the fecal microbiome. Following feature selection via minimum redundancy maximum relevance, random-forest models were constructed for single- and multi-omics and performances were evaluated. The models were externally validated in an independent prospective cohort of treatment-naive children and young adults with CD treated with EEN. The discovery cohort consisted of 50 children (mean ± SD age 14.3 ± 2.7 years), of whom 34 (68%) responded to EEN. Combining complementary signals from host metabolism, gut microbiota, and lipid profiles from serum and stool in a multi-omics ML model yielded a model for predicting treatment response (training accuracy 94%; 95% CI, 82%-100%). Key predictive features included serum metabolites (2-hydroxyglutaric acid, Cer[d18:0/22:0], and HexCer[d18:1/d26:1]), fecal metabolites (3-methyladipic acid, DG[16:0 20:0], PC aa C42:2), and microbial taxa (family Bifidobacteriaceae and genus CAG-56). The validation cohort consisted of 21 patients of whom 12 (57%) responded to EEN. The multi-omics model performance achieved an area under the receiver operating characteristic curve (AUROC) of 0.81 (95% CI, 0.6-1.0). Clinical and endoscopic features did not improve the predictive ability of the model. As a proof-of-concept, we showed that integrated multi-omics ML models can predict EEN response in pediatric CD patients, supporting their potential use in precision nutrition and personalized care strategies. This study developed and externally validated a multi-omics machine-learning model integrating serum and fecal metabolomics, lipidomics, and microbiome data to predict pediatric Crohn disease response to exclusive enteral nutrition, achieving high accuracy. This study advances personalized medicine in pediatric IBD.
Azulay A, Gotesdyner L, Aharoni-Frutkoff Y, Focht G, Talmor Y, Borenstein E, Plotkin L, Orlanski-Meyer E, Lev-Tzion R, Ledder O
Deep Learning-Driven Analysis and Quantification of Histopathological features in a DSS-induced Colitis Mouse Model. The American journal of pathology | 2026-05-04
Dextran-based colitis model has been used extensively to study the pathophysiology of inflammatory bowel disease, including ulcerative colitis and Crohn’s disease. Histological studies of animal colon sections require an unbiased scoring to yield meaningful outcomes. These examinations tend to be tedious, time consuming, and influenced by inherent human bias, which can be reduced with digital pathology tools. In this study, a deep learning-based classifier was used to identify and quantify key histological features in colon sections from a dextran sodium sulfate-induced colitis mouse model. The artificial intelligence (AI)-based classifiers were trained on HALO, an interactive human-in-the-loop image analysis platform, to sequentially identify tissues, mucosa, submucosa, and lymphoid tissues followed by quantification of different levels of tissue damage and cell infiltration within subregions, as well as goblet cell numbers and several cell types based on nuclear phenotyping. AI-based assessments could accurately identify key pathological features and detect alleviation of the damage. This quantitative AI-based assessment of tissue damage exhibited a good correlation and better sensitivity to detect histopathological changes in comparison to pathologist assessment. This proof-of-concept study successfully established the efficiency of machine learning-based classifiers in characterizing disease pathology and their utility during the initial phases of drug discovery.
Doelemeyer A, Wieczorek G, Zierer J, Buffet D, Beckmann N, Amini P
Deciphering the macrophage ferroptosis regulatory network: construction of an ulcerative colitis diagnostic model and investigation of the immune microenvironment based on single-cell and transcriptomic data. Frontiers in immunology | 2026-04-22
Ulcerative colitis (UC) is a chronic inflammatory bowel disease manifested as persistent mucosal inflammation and immune dysregulation. As key regulators of intestinal immune homeostasis, macrophages are pivotal in the amplification of inflammation and tissue repair in UC. However, the molecular mechanisms associated with ferroptosis in macrophages remain unclear. We integrated single-cell and bulk colonic transcriptomes to map ferroptosis-associated programs in UC macrophages, prioritized candidate regulators using network/ML frameworks, and performed targeted experimental validation. We identified a ferroptosis-associated transcriptional program enriched in UC macrophages and derived a four-gene signature (HIF1A, S100A8, CYBB, GLS) linked to redox/iron stress. Among them, CYBB encodes NOX2 (the catalytic subunit of NADPH oxidase), and emerged as a key node associated with enhanced oxidative/iron stress and coordinated changes in ferroptosis-related markers in macrophages. This study systematically delineates the ferroptosis-associated transcriptional network in macrophages of UC, providing a systems-level framework linking macrophage redox/iron imbalance to ferroptosis vulnerability in UC and nominating CYBB-centered pathways for mechanistic interrogation and stratification-oriented biomarker development, thereby offering novel theoretical insights for immune metabolism mechanisms and targeted therapies in UC.
Zhang Y, Chen Z, Zhang S, Chen Y, Xie C, Xiao Q, Fang T
Phage Therapy in Gastrointestinal Diseases: Current Status and Challenges.Review International journal of molecular sciences | 2026-04-20
A phage is a virus that targets bacteria with high precision. While phage therapy provides a targeted alternative to broad-spectrum antibiotics, it is not completely free from the challenges of antimicrobial resistance, as phages can facilitate the horizontal transfer of resistance genes through transduction and promote the growth of phage-resistant strains. Nonetheless, within the One Health framework, the strategic use of phages remains a vital and promising tool for addressing the global antimicrobial resistance crisis. This paper reviews current research on phage therapy for gastrointestinal diseases such as cirrhosis, enteritis, and Helicobacter pylori infection. It also details how phages help regulate gut microecological balance and discusses how phage dysbiosis can lead to innate immune dysfunction and worsen conditions like inflammatory bowel disease. The review summarizes both the therapeutic potential and limitations observed in clinical trials and fundamental studies. Transitioning from laboratory research to clinical practice is hindered by multiple complex challenges, including the stomach’s extreme acidity, physical entrapment by the intestinal mucus layer, the rapid co-evolution of bacterial resistance, and ecological risks associated with temperate phages. To overcome challenges like gastrointestinal barrier tolerance and address ethical, technical, and practical hurdles for clinical use, the paper outlines treatment strategies for specific conditions and highlights future directions, providing guidance for employing phages in digestive system disease management. These future innovations focus on integrating artificial intelligence-driven precision matching, advanced bioengineering for durable delivery systems, and multimodal combination therapies to safely modulate the intestinal microecology.
Zhang S, Zhang Y
IBD-associated Neoplasia (5 papers)
Th9 cells at the intersection of IBD and colorectal cancer: a context-dependent factor in carcinogenesis.Review Inflammation and regeneration | 2026-05-07
The differentiation of naïve T cells into the Th9 phenotype is driven by the synergistic effects of IL-4 and TGF-β, leading to the secretion of their hallmark cytokine, interleukin-9 (IL-9). Known for their critical roles in mucosal immunopathology, Th9 cells are particularly prominent in the gastrointestinal tract, where they contribute to autoimmunity, inflammation, and tissue damage. Recent studies have highlighted the paradoxical role of Th9 cells in colorectal carcinogenesis, revealing that their function is highly context-dependent. In the chronically inflamed microenvironment of inflammatory bowel disease (IBD), Th9 cells exhibit pro-tumorigenic functions. Th9 cells drive the transition to colitis-associated cancer (CAC) by impairing intestinal barrier integrity and promoting epithelial cell survival through PU.1/IL-6/STAT3 signaling and direct oncogene upregulation. Conversely, in sporadic colorectal cancer (CRC), Th9-derived IL-9 exerts anti-tumorigenic effects by enhancing immune surveillance, specifically through the recruitment and activation of mast cells and CD8 + cytotoxic T lymphocytes. Given the complex and often contradictory reports in the literature, this review provides an in-depth analysis of the distinct molecular mechanisms by which Th9 cells shape the tumor microenvironment. By explicitly distinguishing between inflammation-driven carcinogenesis (CAC) and sporadic CRC, this article aims to reconcile current literature and discover emerging therapeutic strategies, such as targeted metabolic reprogramming, to selectively suppress pathogenic Th9 cells without compromising systemic anti-tumor immunity.
Afrough N, Soltani A, Khosravi M, Yadollahi N, Khodadadi A, Shohan M
Evaluation of Obesity as an Independent Risk Factor for Colorectal Dysplasia Development in Inflammatory Bowel Disease: A Matched Case-Control Study. Digestive diseases and sciences | 2026-05-05
Chronic intestinal inflammation is a well-established driver of colorectal dysplasia in inflammatory bowel disease (IBD). However, the role of metabolic factors such as obesity remains poorly understood. We evaluated whether chronic obesity, measured using five-year longitudinal body mass index (BMI), is independently associated with colorectal dysplasia in patients with IBD. We conducted a retrospective 1:1 matched case-control study at a tertiary academic center. Adult patients with ulcerative colitis (UC) or Crohn’s disease (CD) who underwent surveillance colonoscopy between 2019 and 2025 were included. Cases had biopsy-confirmed colorectal dysplasia (indefinite, low grade, or high grade). Controls were dysplasia-free and matched by age (± 5 years), sex, and IBD subtype. Obesity was defined as a mean body mass index (BMI) ≥ 30 kg/m2 using all outpatient measurements over a five-year period prior to the index colonoscopy. Multivariable conditional logistic regression was used to evaluate the association between obesity and dysplasia, adjusting for established dysplasia risk factors and surveillance-related variables. A total of 312 patients were included (156 dysplasia cases and 156 matched controls). Dysplasia cases had significantly longer IBD duration compared with controls (median 12.1 vs. 8.0 years, p < 0.01) and were more likely to have a history of prior colorectal dysplasia (16.0% vs. 3.8%, p < 0.01). In multivariable analysis, obesity was independently associated with colorectal dysplasia (adjusted odds ratio [aOR] 2.23, 95% CI 1.08-4.57). Longer disease duration (aOR 1.05 per year, 95% CI 1.02-1.08) and prior dysplasia (aOR 4.88, 95% CI 1.69-14.06) were also independently associated with dysplasia. In a secondary model adjusting for additional surveillance-related and structural colonic factors, obesity remained significantly associated with dysplasia (aOR 2.11, 95% CI 1.05-4.24). Obesity is independently associated with colorectal dysplasia in patients with IBD, suggesting that metabolic factors contribute to neoplastic risk beyond traditional inflammation-driven pathways. Incorporation of metabolic risk into dysplasia risk stratification may improve CRC prevention strategies in IBD.
Luke N, Echeverria C, Udaikumar J, Delau O, Faye A, Axelrad J
LL-37: Biological Mechanisms and Emerging Therapeutic Applications in Intestinal Disease.Review Immunity, inflammation and disease | 2026-05
Human cathelicidin peptide LL-37 is encoded by the CAMP gene and plays a key role in innate immunity. It maintains intestinal homeostasis through antibacterial, immunomodulation, and tissue repair functions. This paper reviews the multiple functions of LL-37 in the intestinal-immune axis and its contribution to intestinal immune homeostasis. A large amount of evidence shows that the biological effect of LL-37 is highly dependent on the environmental background, and its effects vary with peptide concentration, receptor binding status, disease stage, and local microenvironment. This article reviews the latest findings of the dual role of LL-37 in inflammatory bowel disease (IBD) and colorectal cancer (CRC), and focuses on the conditional mechanism of the transformation of its activity from protective to pathogenic. We also discuss the interaction between LL-37 and intestinal microbiota, focusing on how microbial signals and host peptides can coordinate to regulate mucosal immunity. At the same time, this article examines the key obstacles to the therapeutic application of LL-37 and its clinical promotion: cytotoxicity, rapid degradation by proteases, and drug resistance. We have further explored new strategies to overcome these challenges in the near future, including peptide engineering, nanocarrier delivery systems, and combined therapy. These findings together position LL-37 at the intersection of intestinal immunity and microbial ecology, providing a theoretical basis for its therapeutic application in IBD, CRC and infectious colitis.
Liu Q, Xu P, Zhang C
Additional Crypt Phenotypes Lined With High-Grade Cellular Dysplasia in Protruding Growths in Ulcerative Colitis. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica | 2026-05
Two crypt phenotypes (ACP): crypt rings in tandem (CRT) and crypts with lateral budding’s (CLB’s) were recently found interpolated amidst generally accepted crypt phenotypes (GACP, i.e., tubular, tubulovillous, villous and serrated). The frequency of cases with UC-PDG, with CRT and with CLB’s in GACP and in UC-associated sporadic adenomas (UC-aspa) was recorded. The possibility that the presence of ACP could increase histological discrimination between UC-PDG and UC-aspa was also explored. Two hundred digitalized biopsy-cases were investigated: 100 with UC-PDG and 100 with UC-aspa. Six GACP and two types of cellular dysplasia: low-grade (LGD) and high-grade dysplasia (HGD) were found. CRT and CLB’s were present in 66% of the 200 cases. A significantly higher number of cases with villous phenotype wihout or with HGD, with CLB’s phenotype without or with HGD, and with tubulovillous phenotype with HGD were found in UC-PDG than in UC-asta. Several authors found no significant difference in the histological characteristics between UC-protruding dysplastic lesions and US-aspa. This work reveals, however, that the different number of cases with the above-mentioned histological parameters present in each group permitted to discriminate between UC-PDG and UC-asta.
Rubio CA, Firmbach D, Matek C, Vieth M, Lang-Schwarz C
Surgical management of ulcerative colitis-associated colorectal cancer in a 20-year period, a single-centre study. Pathology oncology research : POR | 2026-04-22
The incidence of inflammatory bowel disease is on the rise. Inflammation that persists for years or decades may involve the risk of malignant transformation. Indeed, it is the cause of death in 15% of the UC patient population. Proctocolectomy followed by ileal pouch-anal anastomosis is the accepted surgical procedure. Our study objective was to retrospectively assess the occurrence and surgical treatment of UC-associated colorectal cancer cases in our institute and analyse survival data. In our department, 39 patients (12 female and 27 male patients) underwent surgery for UC-associated colorectal cancer between 1 January 2005 and 1 January 2025. Their mean age was 55 ± 13.4 years. Risk factors for the disease, examination results, types of surgery, perioperative and long-term surgical results, and survival measures were assessed retrospectively. The latter were determined using the Kaplan-Meier analysis. Thirty-nine patients were diagnosed with UC at a mean age of 35.7 ± 16.7 years, and an average of 19.4 ± 12.3 years passed between the diagnosis of UC and the first surgical intervention. Regular endoscopies were performed in only 66% of our patients. Preoperative staging confirmed distant metastases in 12 patients (30.7%). Patients underwent 34 elective and 5 emergency surgeries. The mean follow-up duration was 40.2 ± 51.7 months. Only 7 patients (17.9%) had a T1 lesion. Lymph node involvement was confirmed in 17 cases (44.5%), whereas 12 patients (30.7%) showed dissemination. Adjuvant chemotherapy was administered in 23 cases (58.9%), and follow-up was recommended for 13 patients (33.3%). During the study period, 17 of the 39 patients died. The mean survival after the surgical procedure was 98.6 months (8.2 years). Survival was significantly shorter in patients who had undergone emergency surgery, were active smokers, suffered from PSC, and lacked gastroenterological follow-up. Based on our experience, it is especially important for UC patients to receive close gastroenterological follow-up in specialised centres and undergo regular colonoscopies and for staff to evaluate biopsy samples properly and perform the appropriate surgical procedures in due time, preferably proctocolectomy and creation of IPAA with a minimally invasive method.
Tajti J, Libor L, Ábrahám S, Simonka Z, Maráz A, Paszt A, Molnár T, Oláh J, Lázár G
Extraintestinal Manifestations (4 papers)
Advanced therapies for extraintestinal manifestations of IBD: a systematic review and meta-analysis.★ Inflammatory bowel diseases | 2026-05-11
Extraintestinal manifestations (EIMs) occur in one-fifth of patients with inflammatory bowel diseases (IBDs) (Crohn’s disease[CD]; ulcerative colitis [UC]). As advanced therapies (ATs) for IBD become more targeted, effectiveness for luminal disease may not be extrapolatable to EIMs. We conducted a systematic review to evaluate the efficacy of ATs on EIMs in IBD. We conducted searches in PubMed/Embase (inception March 2025) for studies of any of the 5 FDA approved AT classes (tumor necrosis factor [TNF] antagonists, Janus kinase [JAK] inhibitors, anti-integrins, anti-interleukins [anti-ILs], and S1P receptor modulators) for musculoskeletal (arthritis, arthralgias), dermatologic (erythema nodosum, pyoderma gangrenosum), or ocular EIMs in patients with IBD. The primary outcome was clinical improvement. The pooled improvement rates by EIM type and AT class were calculated using a random effects model to account for anticipated heterogeneity. A total of 49 studies were included in the final analysis (6 randomized clinical trials [RCTs], 1 pooled analysis of clinical trials, and 42 observational studies). For musculoskeletal EIMs, TNF antagonists achieved response in 61% of patients, with higher response rates for peripheral (73%) than axial (57%) arthritis. JAK inhibitors were similarly effective (65%) while vedolizumab had significantly lower efficacy (42% improvement), particularly for axial arthritis (12%). For dermatologic EIMs, systemically directed ATs had high efficacy (TNF antagonists 89%, anti-IL 91%). There was a paucity of data on ocular EIMs. Systemically directed ATs (TNF-antagonists, JAK inhibitors, anti-ILs) demonstrated strong efficacy for musculoskeletal or cutaneous EIMs; vedolizumab achieved clinical response in lower rates, particularly for axial arthritis.
Sachdeva K, Manik D, Chhibba T, Ananthakrishnan A
Colorectal dysplasia and malignancy outcomes in primary sclerosing cholangitis and inflammatory bowel disease requiring liver transplantation and colectomy: A multicenter study. Surgery | 2026-05-08
Literature guiding management of patients with primary sclerosing cholangitis and inflammatory bowel disease undergoing liver transplantation for primary sclerosing cholangitis and total abdominal colectomy for dysplasia or malignancy is limited. This study describes patterns of colorectal dysplasia, malignancy, and ileal pouch anal anastomosis outcomes for these patients. Electronic health records from 9 centers were retrospectively reviewed. Adult patients who underwent liver transplantation for primary sclerosing cholangitis and total abdominal colectomy for inflammatory bowel disease with dysplasia or malignancy were eligible. Descriptive statistics were analyzed between 2 groups: total abdominal colectomy before liver transplantation (total abdominal colectomy first) and liver transplantation before total abdominal colectomy (liver transplantation first). Of 50 eligible patients, 30 underwent total abdominal colectomy for dysplasia and 20 for malignancy. Between the total abdominal colectomy first and liver transplantation first groups, there were no significant differences in malignancy as the indication for total abdominal colectomy (11 [50.0%] vs 9 [33.3%]; P= .26), T3+ disease (5 [50.0%] vs 2 [25.0%]; P= .37), or distant metastasis at the time of diagnosis (none). Nodal involvement was higher in the liver transplantation first group (5 [50.0%] vs 0 [0.0%]; P = .04). Colorectal cancer recurrence and 5-year overall survival were similar between groups (2 [18.2%] vs 2 [22.2%] and 7 [87.5%] vs 6 [75.0%]; all P= 1.0, respectively). Kaplan-Meier survival analysis showed no significant difference between the groups (P = .4). Both groups had a 54.5% rate of pouchitis. There was only 1 pouch failure. Despite more advanced disease at presentation for liver transplantation first patients, 5-year overall survival was comparable to total abdominal colectomy first patients and the general literature. Patients with ileal pouch anal anastomosis had similar rates of pouchitis to prior studies and low pouch failure.
Galloway JL, Matar AJ, Muralidharan VJ, Steinhagen R, Weaver L, Gaertner WB, Schultz KS, Leeds IL, Lovasik BP, Chapman WC
Serum anti-Saccharomyces cerevisiae antibody is associated with disease severity in patients with primary sclerosing cholangitis. Digestive diseases (Basel, Switzerland) | 2026-05-05
Primary sclerosing cholangitis (PSC) is a chronic liver disease accompanying inflammatory bowel disease (IBD). Anti-Saccharomyces cerevisiae antibody (ASCA) is a serological marker associated with aggressive IBD phenotype. Data on the association between ASCA and liver outcomes remain elusive. We aimed to explore whether ASCA seropositivity is associated with liver disease severity in people living with PSC-IBD. We conducted a retrospective study on adult patients with PSC-IBD at a tertiary center, between 2010 and 2023. Medical records were reviewed for demographics, clinical and laboratory data. Severity of liver disease was assessed using the Amsterdam-Oxford prognostic model (AOM) and liver stiffness measurement (LSM), assessed by vibration-controlled transient elastography (FibroScan®). The cohort comprised of 58 subjects with PSC-IBD and an available ASCA result. Thirty patients were diagnosed with ulcerative colitis (UC) and 28 with Crohn’s disease (CD). Six of 30 (20%) patients with UC and 14 of 28 patients (50%) with CD had positive ASCA. In a univariate analysis AOM (p=0.021) and LSM (p=0.018) were significantly higher in those positive for ASCA. In a multivariable model, ASCA positivity remained significantly associated with higher AOM score (p=0.026) and a higher LSM (p=0.036), even after adjustment for IBD subtype and disease duration. In subjects with IBD with concomitant PSC, the presence of serum ASCA is associated with increased liver stiffness and AOM score, well-known markers for disease severity and reduced transplant-free survival. Further studies are warranted to validate these findings and to explore the biological mechanism underlying this association.
Zmora N, Bannon L, Tzadok R, Nachmias N, Leibovitzh H, Zigmond E
Comparative Outcomes of Primary Sclerosing Cholangitis With and Without Comorbid Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis. Digestive diseases and sciences | 2026-05-05
Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease frequently associated with inflammatory bowel disease (IBD). While PSC with IBD is recognized as a distinct entity, comparative outcomes of PSC with IBD versus PSC alone remain uncertain. This systematic review and meta-analysis aimed to compare clinical outcomes in patients with PSC with and without comorbid IBD. We conducted a systematic review and meta-analysis following PRISMA and MOOSE guidelines. MEDLINE, PubMed, Embase, Scopus, and CENTRAL were searched to October 2025. Eligible studies included adults with PSC stratified by IBD status, reporting risk of all-cause mortality or liver transplant, malignancy, graft survival, or recurrent PSC. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled using random-effects models. Twenty-six studies involving 23,837 patients (16,502 PSC-IBD; 7,335 PSC only) were included. PSC-IBD was associated with a significant decrease in all-cause mortality or liver transplantation compared with PSC alone (HR 0.77, 95% CI, 0.62-0.97). Subgroup analysis showed that both PSC with Crohn’s disease (HR 0.67, 95% CI 0.54-0.84) or ulcerative colitis (HR 0.72, 95% CI 0.55-0.95) had a significantly lower risk of all-cause mortality or liver transplantation compared to PSC alone. Indeterminate colitis carried a higher risk compared with Crohn’s disease (HR 1.57, 95% CI 1.00-2.4). PSC-IBD was associated with increased risk of hepatopancreatobiliary cancer (HR 2.37, 95% CI 1.35-4.15). There was no significant difference in risk of recurrent PSC between PSC-IBD and PSC only. PSC-IBD may be associated with a lower risk of all-cause mortality and liver transplant compared to PSC alone, although these findings should be interpreted cautiously given the limited number of studies for several outcomes. Further prospective studies are needed to refine risk stratification.
Nguyen B, Quon S, Chahal D
Genetics & Genomics (4 papers)
The multifaceted regulation of autophagy protein ATG16L1 and its implications in human diseases.Review Autophagy | 2026-05-10
ATG16L1 (autophagy related 16 like 1) is a core macroautophagy/autophagy protein essential for autophagosome formation. It also functions in non-canonical autophagy pathways such as LC3-associated phagocytosis (LAP) and in other processes including immunity, inflammation, and membrane trafficking. This review synthesizes recent advances and proposes that ATG16L1 functions as a central molecular integrator governed by a multi-layered regulatory code. This framework includes genetic polymorphisms, transcriptional control, and diverse post-transcriptional and post-translational mechanisms. We detail how these regulatory layers collectively fine-tune ATG16L1 function in response to cellular stress. Dysregulation of this network contributes broadly to human diseases including inflammatory bowel disease, cancer, and neurodegenerative disorders. Notably, the functional impact of specific regulatory events is highly context dependent, a principle exemplified by the Crohn disease-associated T300A polymorphism. Deciphering this regulatory landscape and its crosstalk with both autophagy-dependent and autophagy-independent functions positions ATG16L1 as a pivotal node in cellular homeostasis and as an emerging therapeutic target.
Wei F, Liu Z, Yu X, Sun Y, Zhao Y, Wang Y, Feng Z, Zhao X, Ke X, Yang A
SOCS1 Haploinsufficiency in a Patient with Granulomatous Interstitial Lung Disease and Inflammatory Bowel Disease-like Disease. Clinical and experimental immunology | 2026-05-08
SOCS1 haploinsufficiency is an inborn error of immunity with dysregulated JAK-STAT signaling and heterogeneous autoimmune, infectious, and inflammatory phenotypes; its spectrum and management remain unclear. We report a 29-year-old woman with a novel heterozygous SOCS1 variant (c.494C>T; p.Pro165Arg) identified by whole-exome sequencing. Variant impact was assessed in silico (CADD, conservation mapping, AlphaFold3, PremPS) and functionally by measuring total and phosphorylated STAT1 expression in patient vs control cells at baseline and after IFN-γ stimulation. We also reviewed data from 20 previously reported SOCS1-deficient patients. The patient had granulomatous lymphocytic interstitial lung disease (GLILD), rheumatoid arthritis, IBD-like enteropathy, and hypogammaglobulinemia, initially diagnosed with CVID. GLILD responded to rituximab; sirolimus was ineffective for enteropathy. Segregation revealed an asymptomatic father carrying the same variant. The patient was found to have an additional heterozygous TACI gene variant. Post-stimulation flow cytometry showed higher STAT1 (24.7 vs 5.8 MFI) and p-STAT1 (43.4 vs 2.4 MFI) levels; however, these differences were not statistically significant (p>0.05). Structural modeling predicted SH2-domain destabilization (ΔΔG +1.16 kcal/mol). Literature synthesis for SOCS1 deficiency patients (n=21) showed median symptom onset of 8 years (range 5 months-44 years), autoimmune diseases (immune thrombocytopenia, psoriasis, etc.), and frequent immunophenotypic abnormalities: lymphopenia 4/8 (50%); high IgE 5/7 (71.4%); low CD3+ 11/17 (64.7%); CD4+ 6/19 (31.5%); CD8+ 5/17 (29.4%); B cells 5/17 (29.4%); and NK cells 4/19 (21%). SOCS1 haploinsufficiency presents heterogeneous phenotypes with variable penetrance. Early genetic testing and targeted interventions, such as JAK inhibitors or cytokine-blocking biologics, may improve outcomes.
Sonmez G, Yaz I, Ustun C, Şahin A, Aliyeva G, Babaoglu E, Özden G, Halacli SO, Cagdas D
Activation of GABABR alleviates DSS-induced colitis in mice by rebalancing inflammatory responses and antioxidant capacity through IRAK-M. International immunopharmacology | 2026-05-04
The pathogenesis of inflammatory bowel disease is complex, involving key contributors such as inflammatory factors and oxidative stress. While the gamma-aminobutyric acid B receptor (GABABR) is recognized for its potential anti-inflammatory and antioxidant capabilities, its specific role in colitis requires further elucidation. This study aimed to determine whether GABABR activation could alleviate colitis by modulating these interconnected pathways. Our findings demonstrate that dextran sulfate sodium-induced colitis significantly downregulates GABABR expression in colonic tissues, a finding confirmed in lipopolysaccharide-stimulated Caco-2 cells. Pharmacological activation of GABABR with baclofen effectively mitigated overall disease severity by ameliorating clinical symptoms and preventing colon shortening; it also preserved mucosal architecture while restoring goblet cell numbers and modulating mast cell populations. Mechanistically, experiments across both in vivo and in vitro models demonstrated that these multifaceted protective effects were primarily mediated through the upregulation of interleukin-1 receptor-associated kinase M (IRAK-M). Specifically, GABABR activation produced coordinated effects by significantly suppressing pro-inflammatory cytokines including IL-1β, IL-6, IL-17A, IL-22, and TNF-α, while potently countering oxidative stress via elevation of key antioxidants including HO-1, NRF2, and GPX4 and simultaneous inhibition of iNOS. Most importantly, genetic knockout of IRAK-M completely exacerbated all pathological aspects of colitis, encompassing clinical severity, histological damage, inflammatory cytokine storm, and oxidative imbalance, thereby definitively confirming IRAK-M as the essential downstream mediator. Consequently, these results establish that GABABR alleviates colitis by targeting IRAK-M to coordinately enhance antioxidant responses and inhibit inflammation, highlighting the GABABR signaling as a promising therapeutic target.
Huang Z, Lao R, Ye Y, Xiu Y, Xie Y, Su R, Lu A, Chen Y, Liao J, Huang Y
The gut-lung axis: pathological crosstalk and inter-organ communication in chronic obstructive pulmonary disease and inflammatory bowel disease.Review Frontiers in immunology | 2026-04-22
The significant bidirectional comorbidity risk and extensive subclinical involvement observed between chronic obstructive pulmonary disease (COPD) and inflammatory bowel disease (IBD) underscore the pivotal role of the “gut-lung axis” in cross-organ pathological crosstalk. Here, we comprehensively review the molecular and immunological mechanisms driving this comorbidity. Genome-wide association studies (GWAS) have substantiated genetic pleiotropy that underpins a shared susceptibility to mucosal defense deficits. The “common mucosal immune system” (CMIS), rooted in embryonic homology, constitutes the anatomical basis for this pathological interplay, wherein aberrant immune cell homing, Th17/Treg imbalance, and the cross-organ trafficking of innate lymphoid cells (ILCs) mediate the distal dissemination of inflammation. Furthermore, gut dysbiosis-induced depletion of short-chain fatty acids (SCFAs), acting in concert with systemic hypoxia and the IL-23/IL-17 axis, potentiates synergistic injury to the gut-lung barriers. We highlight the reciprocal, bidirectional causality of this “hypoxic loop” and its testable mechanistic predictions for barrier dysfunction. Furthermore, we evaluate pharmacological evidence from drug repositioning, alongside a critical examination of the “hidden axis” of clinical therapies as profound iatrogenic confounders. Elucidating these mechanisms is critical for establishing systemic diagnostic and therapeutic strategies; interventions targeting shared molecular targets and the microbiota hold promise for achieving a simultaneous treatment approach for these distinct pathologies.
Liu X, Yang S, Yan Y, Zhang L, Yang X, Liu L
Guidelines & Consensus (3 papers)
Soluble transferrin receptor as a reliable inflammation-independent marker of iron deficiency in Crohn’s disease and ulcerative colitis.★ Inflammatory bowel diseases | 2026-05-09
Iron deficiency is a common complication in inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD). However, standard iron markers are influenced by inflammation, complicating the diagnosis of true iron deficiency. Soluble transferrin receptor (sTfR) has been proposed as a more reliable, inflammation-independent marker of iron demand. This study aimed to assess the utility of sTfR in identifying iron deficiency without anemia (IDWA). The ID_IBD study was a multicenter, cross-sectional study. Iron status was classified using two approaches: the ECCO consensus definition, focusing on ferritin thresholds adjusted for inflammatory markers (C-reactive protein [CRP] and fecal calprotectin [FCAL]), and a stricter definition that adds transferrin saturation to the ECCO criteria. sTfR levels were compared across groups, and ROC curve analysis was used to identify optimal diagnostic cut-offs. This analysis included 411 IBD patients (130 UC, 281 CD) and 178 controls. sTfR showed no correlation with CRP or FCAL. In UC, patients with IDWA had significantly higher sTfR levels (median 1.20 mg/L, IQR 1.02-1.42) compared to non-IDWA patients (median 1.05 mg/L, IQR 0.92-1.22; P = .013). Anemic UC patients also showed elevated sTfR levels (median 1.27 mg/L, IQR 1.14-1.59) compared to non-IDWA individuals (P < .001). In CD, sTfR did not significantly differ between IDWA and non-IDWA patients but was significantly higher in anemic patients (P = .003). sTfR appears to be an inflammation-independent marker of iron status in IBD. It showed greater potential for identifying IDWA in UC, while in CD it mainly reflected increased iron demand in anemia. Overall, sTfR may be useful as a complementary parameter to conventional iron markers. Further longitudinal studies are warranted to validate these findings and assess their clinical utility in IBD. This study suggests that soluble transferrin receptor may serve as an inflammation-independent marker of iron status in Inflammatory Bowel Disease, helping to identify iron deficiency without anemia in ulcerative colitis and reflecting increased iron demand in anemic Crohn’s disease patients.
Portela F, Ministro P, de Sousa HT, Roseira J, Fernandes S, Crespo R, Domingues B, Santiago M, Melo-Miranda R, Dias S
Correction: Human DNA levels in feces reflect gut inflammation and associate with presence of gut species in IBD patients across the age spectrum. Microbiome | 2026-05-08
Abstract not available.
Mazzoni C, Ochana BL, Orlanski-Meyer E, Ya’acov AB, Focht G, Harpenas E, Shmorak S, Ledder O, Lev-Tzion R, Shemer R
Construction and clinical validation of a Team STEPPS-based discharge planning program for patients with inflammatory bowel disease.Clinical trial Frontiers in medicine | 2026-04-20
The transition from hospital to home is a high-risk period for patients with Inflammatory Bowel Disease (IBD). This study aimed to develop and preliminarily validate a structured discharge planning program for patients with IBD by applying the Team STEPPS framework. This study employed a sequential two-phase, mixed-methods design. First, a Team STEPPS-based discharge planning program was rigorously developed using Delphi method between August and October 2023. Subsequently, a randomized controlled trial was conducted from October 2023 to March 2024 to validate the program. Ninety eligible inpatients were randomly assigned to an intervention group (n = 45) receiving the structured Team STEPPS program or a control group (n = 45) receiving standard care. The primary outcome was discharge readiness, assessed at the time of discharge. Secondary outcomes included the quality of discharge teaching, measured at discharge, and health-related quality of life, evaluated at baseline, discharge, and 30-day follow-up. Longitudinal outcomes analyzed via linear mixed-effects models. All 90 enrolled participants completed the study. The Delphi process successfully achieved expert consensus, resulting in a structured discharge program with all items meeting predefined criteria (mean importance ≥ 4.0, coefficient of variation ≤ 0.25). In the subsequent randomized controlled trial, baseline characteristics were well-balanced. At discharge, the intervention group exhibited statistically superior outcomes, including significantly higher discharge readiness (103.0 ± 7.3 vs. 94.9 ± 4.7, P < 0.001) and quality of discharge teaching scores (183.6 ± 6.4 vs. 172.7 ± 5.0, P < 0.001). Longitudinal analysis of health-related quality of life revealed a significant group-by-time interaction effect (P < 0.001), with the intervention group demonstrating a greater magnitude of improvement. The model estimated an incremental benefit of the intervention of 9.2 points (95% CI: 5.7-12.7) at the 30-day follow-up compared to standard care. A Team STEPPS-based discharge planning program was successfully developed and shown to be effective, significantly improving discharge readiness, the quality of discharge teaching, and health-related quality of life in patients with IBD. https://www.chictr.org.cn/index.html, identifier ChiCTR2501113716.
Lv P, Li M, Lao L, Li Y, Wang R, Zhang P, Xu L
Pregnancy & Reproductive Health (3 papers)
Maternal influenza infection during pregnancy and subsequent risk of inflammatory bowel diseases in offspring: a nationwide birth cohort study in South Korea.Letter★ Gut | 2026-05-04
Abstract not available.
Choi Y, Kim H, Park J, Yeo D, Kang J, Yon DK
Repeated opioid use during pregnancy in women with inflammatory bowel disease: prevalence and impact on birth outcomes in Denmark.★ Journal of Crohn’s & colitis | 2026-05
In women with IBD, there are few options to treat pain during pregnancy and prescribers sometimes rely on opioids. We investigated the prevalence of repeated opioid use during the pregnancy period as well as the impact on birth outcomes. Using the Danish national registries, we identified pregnancies of women with IBD from January 1, 1997, to June 1, 2023. We defined repeated opioid use as at least two opioid prescriptions with a minimum 30-day interval between them. We examined the prevalence in three separate time periods: (1) nine months before conception; (2) throughout pregnancy; and (3) nine months postpartum, and we calculated adverse birth outcomes. Of 10 904 women with IBD, 237 (2.2%) had repeated use of opioids prior to pregnancy, 220 (2.0%) during pregnancy and 359 (3.3%) postpartum. Women with repeated opioid use prior to pregnancy were significantly more likely to have repeated use during pregnancy (adjusted odds ratio (aOR): 231.50 (95% CI, 159.80-335.36)). Women who had repeated use during pregnancy were significantly more likely to have repeated use during the postpartum period (aOR: 74.98 (95% CI, 53.76-104.57)). Women with repeated use of opioids during pregnancy had statistically significant risks of preterm birth (aOR: 1.87 (95% CI, 1.28-2.74)) and of delivering a small for gestational age infant (aOR: 2.46 (95% CI, 1.41-4.32)). The proportions of women who used repeated opioids prior to pregnancy, during pregnancy, and in the postpartum period were low but consequences for neonates can be severe. Providers should screen for opioid use in this population.
Friedman S, Zeiss K, Wod M, Nielsen J, Nørgård BM
Shifting Towards Empagliflozin First-Line Therapy in Glycogen Storage Disease Type Ib: A Nationwide Real-World Study. Journal of inherited metabolic disease | 2026-05
Neutrophil dysfunction and neutropenia are burdensome findings in glycogen storage disease type Ib (GSDIb). Treatment with granulocyte-colony stimulating factor (G-CSF) often corrects neutropenia but fails to improve clinical symptoms like inflammatory bowel disease (IBD). Recently, empagliflozin (EMPA) was shown to correct the neutrophil dysfunction and its clinical consequences. It is increasingly used as first-line monotherapy, but long-term, real-world data are lacking. This nation-wide retrospective study investigated 42 GSD1b patients (36 children) treated with EMPA as first-line monotherapy and compared them with those receiving combination therapy with G-CSF and treatment-naïve patients (I:EMPA first-line monotherapy [n = 9]; II:G-CSF monotherapy [n = 7]; III:EMPA plus G-CSF [n = 16]; and IV: neither EMPA nor GCSF [n = 10]). Pediatric (P) patients were evaluated separately. In pediatric patients receiving EMPA as first-line monotherapy (P-I) and those with EMPA plus G-CSF (P-III), the frequency of infections, hospital admissions, and IBD was significantly lower than in patients receiving GCSF-monotherapy (P-II) or no treatment (P-IV). Additionally, significantly improved weight gain was observed in P-I. While clinical improvement related to correction of neutrophil dysfunction was seen with EMPA first-line monotherapy (P-I), significant improvement in absolute neutrophil count (ANC) and hemoglobin levels was only seen in P-III with additional G-CSF treatment. In three cases, EMPA was safely paused and subsequently resumed, for example, during pregnancy or liver transplantation. First-line EMPA monotherapy effectively corrects clinical symptoms of neutrophil dysfunction in GSD Ib patients, even in the absence of a statistically significant increase in ANC.
Uçar SK, Mungan NÖ, Gökçay GF, Zeybek AÇA, Kılavuz S, Güneş S, Kardaş F, Kısa PT, Çıkı K, Yavaş AK
Endoscopy & Imaging (non-IUS) (2 papers)
Transfer of faeces in ulcerative colitis 2: improving efficacy - study protocol for a multicentre randomised controlled trial (TURN2 study). BMJ open | 2026-05-05
The interaction between the gut microbiota and the host immune system is implicated in the pathogenesis of inflammatory bowel disease, including ulcerative colitis (UC). Targeting the gut microbiota with faecal microbiota transplantation (FMT) from a healthy donor has shown promise in inducing remission in patients with active UC. However, mixed results and protocol heterogeneity have limited its practical application. Our previous Transfer of Faeces in Ulcerative Colitis; Restoring Homeostasis (TURN) trial found a correlation of clinical response with specific strains and butyrate production. Since most gut microbes, including many butyrate producers, are anaerobes, anoxic processing of donor stool may be essential to increase efficacy of FMT in UC. This trial aims to enhance FMT efficacy by applying strict anoxic processing, selecting donors based on microbial composition and using repetitive dual-route administration. This randomised, double-blind, placebo-controlled, multicentre study evaluates the efficacy of strictly anoxic prepared donor FMT compared with anoxic prepared autologous FMT in patients with mild to moderate active UC. An open-label extension option is available for non-responders in the autologous arm. Included patients will receive 4 weekly FMTs, comprising two double-route administrations (nasoduodenal administration combined with enema) and two single enemas. Donors are selected based on their microbiota profile, informed by our previous TURN trial and literature. A total of 76 patients evaluable for the primary endpoint will be included. The primary endpoint is steroid-free clinical and endoscopic remission at week 8, assessed by the adapted Mayo score. An interim analysis will be conducted midway through the study by a Data Safety Monitoring Board to monitor efficacy and safety. Other outcomes of this study include the evaluation of clinical, endoscopic and histological response. In addition to clinical results, this study aims to provide valuable insights into specific microbial strains, metabolites and mechanisms correlated with response, aiding in the development of future microbial therapies. Ethics approval was obtained from the medical ethics committee of the Amsterdam University Medical Centre in the Netherlands (reference number 2018_057). All participants will provide written informed consent. The results of the trial will be disseminated through publication in a peer-reviewed journal and presentations at (inter)national conferences. Prospectively registered in May 2018 in the Dutch Trial Register (NTR/LTR) as NL7770. Assigned NL-OMON52507 following the transition of the Dutch Trial Register to the Overview of Medical Research in the Netherlands. Also registered at ClinicalTrials.gov (NCT05998213).
Bénard MV, Van Der Spek MJ, Davids M, Visser CE, Zoetendal EG, Rethans B, Zwezerijnen-Jiwa FH, Visschedijk MC, Ponsioen CY, Oldenburg B
Colonoscopy in elderly patients: diagnostic yield, pre-referral assessment and quality indicators in two Swedish cohorts. Scandinavian journal of gastroenterology | 2026-05-03
Colonoscopy in elderly, frail patients requires weighing diagnostic yield against procedure-related risk, but real-world data are limited. We describe outcomes from two Swedish cohorts undergoing non-screening colonoscopy in two regions. We combined aggregated results from two retrospective cohort studies. The Ersta cohort included all patients aged ≥75 years undergoing colonoscopy in 2022 and compared inpatient versus outpatient examinations. The Örebro cohort included all colonoscopies in patients aged ≥80 years during 2016-2018. We extracted data on indications, pre-referral investigations, findings, quality indicators, and short-term mortality. For Örebro, we used previously calculated odds ratios and positive predictive values for significant findings. At Ersta, 1,066 patients aged ≥75 years underwent 1,144 colonoscopies; 40% were performed in inpatients admitted for bowel preparation. Colorectal cancer was diagnosed in 5%, inflammatory bowel disease in 6%, microscopic colitis in 3%, and other colitis in 4%, with similar proportions in inpatients and outpatients. One-year mortality was 6% after inpatient and 1% after outpatient colonoscopy. In Örebro, 565 colonoscopies in patients aged ≥80 years were analyzed. Significant findings occurred in 26.2% (colorectal cancer 18.8%, high-grade dysplasia 4.6%, any colitis 5.0%, with some overlap). Abnormal rectal examination, abnormal abdominal imaging, low ferritin, and positive f-Hb predicted significant disease. Altered bowel habits was the most common indication but had an odds ratio below 1 for significant disease. In elderly Swedish patients, colonoscopy detects colorectal cancer or colitis, but many examinations show benign or no findings. Selection using simple pre-referral tests and life expectancy may reduce low-yield examinations.
van Nieuwenhoven M, Ghaderi S, Backman AS, Nieuwenhoven MV, Backman AS, Höög C, Forsberg A, Hreinsson JP, Bednarska O, de Lange T
Drug Safety & Pharmacovigilance (1 papers)
Discovery, development, and characterization of SPY002 and SPY072, two novel extended half-life monoclonal antibodies targeting TL1A: in vitro properties, in vivo pharmacology, pharmacokinetics, and preclinical safety. mAbs | 2026-05-10
TL1A is a proinflammatory cytokine in the tumor necrosis factor (TNF) superfamily that signals via DR3 on T helper cells, innate lymphoid cells, and fibroblasts. Dysregulated TL1A signaling has been hypothesized to affect multiple immune-mediated diseases, with clinical proof of concept demonstrated in ulcerative colitis and Crohn’s disease. We characterized the binding affinity, specificity, structure, pharmacodynamics, pharmacokinetics, and toxicity profiles of SPY002 and SPY072, two novel extended half-life monoclonal antibodies that inhibit TL1A. SPY002 and SPY072 demonstrated selective, high-affinity binding to human TL1A (KD ≈ 31-35 pM) and potent functional inhibition of DR3 signaling. Based on Fc modifications, SPY002 and SPY072 showed attenuated Fc effector function and increased FcRn binding at acidic pH (5.8). Both antibodies exhibited enhanced PK profiles in nonhuman primates, resulting in predicted human half-lives that support quarterly or biannual dosing. In toxicity studies, no drug-related adverse effects were observed with either antibody at exposures >10 times those anticipated in clinical trials. In a rat collagen-induced arthritis model, anti-TL1A antibody treatment effectively reduced arthritis severity, with similar efficacy to the TNF antagonist etanercept. In humanized mouse Imiquimod-induced psoriasis and 2,4,6‑trinitrobenzene sulfonic acid colitis models, anti-TL1A demonstrated similar efficacy to anti-IL-23 and anti-TNF antibodies. These findings characterize two novel extended half-life TL1A antibodies and support the ongoing Phase 2 clinical development of SPY002 and SPY072 for immune-mediated diseases such as inflammatory bowel disease and rheumatic diseases.
Siegel M, Zhu E, Rios D, Kang BH, McNally J, Kennedy M, Hew K, Patel P, Ballew O, Giles DH
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