IBD Literature Report
Coverage: November 04, 2026 - November 11, 2026
125
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Therapeutics & Mechanisms (20 papers)
Comparative effectiveness of infliximab and tofacitinib in advanced therapy-naive and -exposed patients with ulcerative colitis: a multicenter real-world study.★ Inflammatory bowel diseases | 2026-11-10
and Aim: Infliximab (IFX) and tofacitinib (TOF) are advanced therapies for ulcerative colitis (UC), but real-world comparative data by prior advanced therapy (AT) exposure remain limited. We compared effectiveness by prior AT exposure. This multicenter retrospective cohort study included adults with UC who initiated IFX or TOF between June 2010 and May 2025. The primary analysis was restricted to May 2018 onward, when both were available in Japan. AT-naive and AT-exposed cohorts were analyzed separately using overlap weighting. The primary outcome was corticosteroid-free clinical remission at week 52. Of 266 patients (137 IFX, 129 TOF), the primary analysis included 76 AT-naive (27 IFX, 49 TOF) and 120 AT-exposed (40 IFX, 80 TOF) patients. Week 14 remission did not differ significantly between treatments in either cohort. At week 52, remission numerically favored TOF in AT-naive patients (IFX, 43.9%; TOF, 64.5%; odds ratio [OR], 2.32; 95% CI, 0.84-6.44; P = .105), whereas remission was higher with TOF in the AT-exposed cohort (IFX, 19.0%; TOF, 38.8%; OR, 2.71; 95% CI, 1.08-6.80; nominal P = .034). Three-year treatment persistence did not differ significantly in either cohort but numerically favored TOF in AT-naive patients (IFX, 39.2%; TOF, 61.5%; hazard ratio, 0.64; 95% CI, 0.31-1.36). Multiple-imputation analyses yielded similar findings. Week 52 remission numerically favored TOF in AT-naive patients and was higher with TOF in AT-exposed patients. Clinically relevant differences in 3-year persistence could not be ruled out, particularly in AT-naive patients. These findings are exploratory.
Mizuta N, Kinoshita N, Kakimoto K, Hara A, Ito H, Hongo H, Moriya K, Numa K, Nakazawa K, Koshiba R
Peripheral T- and B-cell immune signatures associated with response to vedolizumab in ulcerative colitis.★ Inflammatory bowel diseases | 2026-11-06
Vedolizumab (VDZ) blocks integrin α4β7-MAdCAM-1 interactions, limiting leukocyte entry into the gut, yet peripheral-blood immune correlates of clinical response in ulcerative colitis (UC) remain unidentified. Peripheral blood mononuclear cells from healthy controls (HCs) and patients with UC, stratified by VDZ exposure and clinical response, were analyzed using mass cytometry (cytometry by time-of-flight). A 38-marker panel enriched for integrins, chemokine receptors, and activation markers was applied. Major immune populations were interrogated using lineage-specific opt-SNE and FlowSOM clustering. The dataset included 26 HCs, 30 VDZ-naive UC (Nancy index ≥ 2), 8 VDZ-treated non-responders (Nancy index ≥ 2), and 8 VDZ-treated responders (Nancy index <2). No significant differences were detected in myeloid, NK-cell, or TCRγδ+ T-cell compartments. Integrin α4β7+ cells were detected across multiple immune lineages and were enriched in the B-cell compartment. Between-group differences were observed in the CD4+ T-cell and B-cell compartments. VDZ responders showed enrichment of an α4β7+ effector memory CD4+ T-cell subset compared with VDZ-naive UC. In parallel, responders exhibited reduced frequencies of class-switched plasmablast and activated B-cell populations relative to VDZ-naive UC. Integrin-pairing analysis demonstrated that these B-cell populations contained both α4β7+ and α4β1+ cells. In contrast, VDZ non-responders showed enrichment of an α4β7+ atypical-like IgA+ memory B-cell subset relative to responders, VDZ-naive UC, and HCs. Clinical response and non-response to VDZ in UC are associated with distinct circulating T- and B-cell immune phenotypes. Peripheral-blood immunophenotyping may identify correlates of response and non-response. Prospective studies are needed to determine whether these signatures are predictive before VDZ initiation or reflect pharmacodynamic changes after treatment.
Horitani S, Horitani A, Tyler CJ, Naganuma M, Ernst PB, Smith D, Patel DR, Behm B, Yarur A, Rivera-Nieves J
Baseline serum glycoprotein acetylation predicts early but not late relapse after infliximab withdrawal in Crohn’s disease: metabolomic analysis of the STORI and SPARE trials.★ Gastroenterology | 2026-11-06
Abstract not available.
Radford-Smith DE, Anthony DC, Probert F, Colombel JF, Satsangi J, Louis E
Immunometabolic and epigenetic reprogramming in inflammatory bowel disease: from mechanistic circuits to therapeutic targeting.Review Biomarker research | 2026-11-06
Inflammatory bowel disease (IBD) is a chronic, immune-mediated disorder of the gastrointestinal tract and an escalating global public health challenge, particularly in newly industrializing regions. Its etiology and pathogenesis remain incompletely understood, although disrupted homeostasis between the intestinal microbiota and the mucosal immune system is implicated. Macrophages and T cells contribute to the balance between tissue injury and repair. Increasing evidence suggests that metabolic state and epigenetic programs interact to influence immune cell function. Under hypoxic and inflammatory stress, glucose, lipid, and amino acid metabolism can undergo remodeling, including shifts between glycolysis and oxidative phosphorylation, altered fatty-acid utilization, changes in tryptophan and methionine metabolism, and fluctuations in methyl-donor availability. Metabolic cues may influence chromatin regulation and immune signaling through acetylation, methylation, lactylation, palmitoylation, phosphorylation, and other modifications. These processes can affect effector programs, the T helper 17-regulatory T cell balance, macrophage inflammatory gene expression, inflammasome activation, and interleukin-10-related signaling, with potential implications for mucosal barrier repair and inflammatory amplification. However, the causal roles of these metabolic and epigenetic alterations in IBD remain to be clarified: they may contribute to disease initiation, arise as accompanying features of the disease state, or amplify inflammation once it is established. This review synthesizes current advances in metabolic reprogramming and epigenetic regulation in macrophages and T cells, examining immunometabolic nodes that link environmental stress to chromatin remodeling. We further summarize emerging therapeutic strategies targeting metabolic and epigenetic pathways, assess evidence from preclinical and clinical studies, and discuss interventions directed at immunometabolic checkpoints.
Han Y, Yi J, Wang X, Li S, Chen M, Xiao J
Efficacy and safety of ustekinumab and vedolizumab in very early-onset inflammatory bowel disease: A multicenter study from the pediatric inflammatory bowel disease Porto Group of ESPGHAN. Journal of pediatric gastroenterology and nutrition | 2026-11-05
We aimed to assess vedolizumab and ustekinumab efficacy and safety in patients with very-early onset inflammatory bowel disease (VEO-IBD). A retrospective study involving 29 European and North American sites affiliated with the IBD Porto Group of European Society for Paediatric Gastroenterology Hepatology and Nutrition. Clinical and laboratory data were collected from patients with VEO-IBD who commenced vedolizumab or ustekinumab before 6 years of age, between 2014 and 2024. Ninety-six patients (60.4% females) were included (58 ulcerative colitis, 29 Crohn’s disease, and 9 IBD-Unclassified). Median (Q1-Q3) age at diagnosis was 2.3 (0.4-4.2) years, 37 (38.5%) patients were diagnosed at age <2 years old. Thirty-seven (38.5%) patients received ustekinumab, 67 (69.7%) vedolizumab, and 11 (11.5%) both drugs. Median (Q1-Q3) follow-up time was 11 (6-26) and 14 (7-39) months for ustekinumab and vedolizumab, respectively. Eighty (84.2%) patients were previously treated with infliximab, 23 (24.2%) with adalimumab, and 20 (20.8%) with both. The median (Q1-Q3) time from diagnosis to vedolizumab and ustekinumab initiation was 15 (9-26) and 20 (11-36) months, respectively. Ustekinumab-treated patients achieved clinical remission in 24.3%, 51.4%, and 40.5% at end of induction, week 26, and week 52, with steroid-free remission in 18.9%, 45.9%, and 35.3%, respectively. Vedolizumab-treated patients achieved clinical remission in 29%, 47.5%, and 40.3%, with steroid-free clinical remission (SFCR) rates of 10.4%, 43.3%, and 37.3% at the same time points. Infectious adverse events were reported in 3 (8.3%) of ustekinumab-treated and 5 (7.6%) vedolizumab-treated patients, none severe. Ustekinumab and vedolizumab demonstrated high therapeutic durability in patients with VEO-IBD; 1-year rates of SFCR were modest.
Scarallo L, Lionetti P, Kierkus J, Collen L, Riedl V, Jakobsen C, Pujol-Muncunill G, Kolho KL, Velasco Rodriguez-Belvis M, Mitrova K
Effects of upadacitinib on lipid profiles and their relationship with inflammation in patients with inflammatory bowel disease: a real-world longitudinal cohort study.★ Inflammatory bowel diseases | 2026-11-05
Upadacitinib (UPA), a selective Janus kinase 1 inhibitor, is approved for moderate-to-severe inflammatory bowel disease (IBD). JAK inhibitors affect lipid metabolism, but longitudinal real-world data on lipid changes during UPA therapy, and their relation to inflammatory activity, are scarce. In this single-center retrospective cohort study, patients with ulcerative colitis or Crohn’s disease treated with upadacitinib were followed for up to 2 years. Serial fasting lipid profiles and inflammatory markers (fecal calprotectin, C-reactive protein [CRP], high-sensitivity CRP) were collected at baseline, end of induction (weeks 8-12), 1 year, and 2 years. Lipid trajectories were analyzed with linear mixed-effects models; paired changes were compared with paired t-tests. Among 159 patients (mean age 43.3 ± 14.0 years; 62.3% male), total cholesterol (TC) rose from 4.19 ± 0.87 mmol/L at baseline to 4.92, 5.03, and 5.21 mmol/L at the end of induction, 1 year, and 2 years (mixed-effects estimates +0.70 to +0.90; all P < .001). Low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) rose in parallel, and the LDL-C/HDL-C ratio did not increase. CRP reductions correlated with lipid rises (Spearman rho = -0.45 to -0.47; all P ≤ .02). No cardiovascular death, myocardial infarction, or stroke occurred (0/159); one venous thromboembolism and 3 hypertension cases were recorded. In patients with IBD treated with UPA, TC and LDL-C rose modestly alongside the resolution of inflammation; HDL-C improved and the LDL-C/HDL-C ratio did not increase. Lipid monitoring and individualized cardiovascular risk assessment are warranted during UPA therapy.
He S, Zhang W, Tian Y, Ge C, Teng G, Li J, Wang H, Dai Y, Tian Y
A Real-World Population Pharmacokinetic Model of Adalimumab in Inflammatory Bowel Disease to Support Model-Informed Precision Dosing in Routine Clinical Practice. European journal of drug metabolism and pharmacokinetics | 2026-11-05
Translating population pharmacokinetic (popPK) models of adalimumab in inflammatory bowel disease (IBD) into clinical practice remains challenging. We aimed to develop a parsimonious popPK model using real-world therapeutic drug monitoring data and perform dosing simulations to guide model-informed precision dosing (MIPD). We conducted a retrospective, longitudinal study of adult IBD patients treated with adalimumab between 2022 and 2024. Serum adalimumab concentrations from routine therapeutic drug monitoring were analysed using nonlinear mixed-effects modelling. Covariates were selected using a stepwise likelihood ratio approach. Model performance was evaluated using goodness-of-fit (GOF) plots, prediction-corrected visual predictive checks (pcVPC), normalised prediction distribution errors (NPDE), sequential Bayesian forecasting analysis, and bootstrap analysis. Monte Carlo simulations estimated the probability of target attainment (PTA) for steady-state trough concentration thresholds of ≥ 8, ≥ 10, and ≥ 12 mg·l⁻1 across different body weight, serum albumin, and dosing scenarios. From 201 patients (56.2% male; 48.6 (±16.2) years), 709 trough concentrations were analysed. A one-compartment model with first-order elimination and absorption (fixed at 0.151·day⁻1) adequately described the pharmacokinetics. Population estimates were apparent clearance (CL/F) 0.288 l·day⁻1 and apparent volume of distribution 5.0 l. Body weight and serum albumin were significant covariates on CL/F, reducing interindividual variability from 59.2% to 42.0%. Model performance was consistent across evaluation methods. Individual parameter estimation was reliable with low CL/F shrinkage (11.1%). Predictive performance was robust: minimal bias (mean prediction error [MPE]: -0.30 mg·l⁻1) and high precision (root mean square error [RMSE]: 3.86 mg·l⁻1). pcVPC demonstrated good agreement (91.0% coverage), and NPDE indicated no structural misspecifications. Sequential forecasting analysis showed that predictive performance improved as more data were incorporated (MPE decreased from 0.37 to 0.03 mg·l⁻1), and precision increased (RMSE decreased from 4.86 to 4.39 mg·l⁻1). Under standard maintenance dosing, PTA ranged from 65.0% to 98.5%, from 36.5% to 93.5%, and from 20.5% to 86.5% for ≥ 8 mg·l⁻1, ≥ 10 mg·l⁻1, and ≥12 mg·l⁻1 respectively. PTA decreased with increasing body weight, lower serum albumin, and more stringent concentration thresholds. This popPK model adequately characterizes adalimumab pharmacokinetics in IBD patients. Its robust predictive performance, which progressively improves as more individual data are incorporated, together with the model-based simulations, supports its potential utility in MIPD, particularly in patients with higher clearance or when higher concentration thresholds are targeted.
Aguilo-Lafarga I, Serés-Noriega T, Gimeno-Ballester V, Roche PAC, Lidon RV, Moros EMS, Gallego S, Lopez SG, Sazatornil MRA
Performance of an infliximab precision-guided dosing tool from a capillary blood-based self-collection device in inflammatory bowel disease patients.★ Inflammatory bowel diseases | 2026-11-05
Infliximab (IFX) trough concentrations are routinely measured to guide dosing and optimize efficacy. Bayesian forecasting tools may enable earlier prediction of trough concentrations, while patient-friendly capillary self-collection devices could improve access to precision-guided dosing (PGD). We evaluated the performance of the PredictrPK IFX platform in forecasting IFX trough concentrations by using serum collected with an upper-arm self-collection device and compared its performance with standard venous blood obtained by phlebotomy. Patients with inflammatory bowel disease (IBD) receiving IFX maintenance therapy were recruited from a single IBD center. Midcycle samples collected via an upper-arm self-collection device and via traditional venipuncture were compared. The IFX clearance was estimated by use of a nonlinear mixed-effects model with Bayesian priors and the predicted IFX levels were compared with measured trough concentrations obtained prior to infusions. Deming regression was used for statistical analysis. The study included 57 patients (61% males, median age, 34 years). The median IFX dose was 10 mg/kg with a median interdose interval of 6 weeks. A total of 97 capillary and venous blood pairs were tested. Concentrations of IFX from venous and capillary blood samples demonstrated strong correlations (R2 = 0.987, Demings = 1.08). There was also a strong association between predicted IFX concentrations and measured IFX trough concentrations. PredictrPK accurately predicted IFX trough concentrations. Capillary self-collection using an upper-arm device yielded results comparable to those from venous blood measurement, which may facilitate increased implementation and accessibility of PGD in clinical practice.
Law CCY, Djalal A, Hopkins M, Trick D, Dervieux T, Rowan C, Colombel JF
Microbial metabolism of methotrexate produces a STAT3 signaling molecule that alleviates gut inflammation. Cell host & microbe | 2026-11-05
Methotrexate (MTX) is a gold standard therapy for inflammatory diseases but has mixed therapeutic success in inflammatory bowel disease (IBD). The gut microbiota impact MTX efficacy and toxicity by metabolizing MTX and altering its bioavailability, yet how inflammation alters this metabolism, and how the resulting metabolites act on the host, remain poorly understood. Here, we find that gut microbes, notably Clostridium asparagiforme, metabolize MTX via carboxypeptidase G2 (CPDG2) to produce deoxyaminopteroic acid (DAMPA). In intestinal epithelial cells, DAMPA preserves mitochondrial health through mitochondrial signal transducer and activator of transcription 3 (STAT3) signaling and enhances mitophagy. DAMPA administration attenuates intestinal inflammation in vivo, and remodels colonic mitochondrial pathways. IBD mouse models show reduced microbial CPDG2 and DAMPA, while patients with IBD show reduced CPDG2 gene abundance and suppressed DAMPA-enriched mitochondrial pathways, potentially explaining MTX outcomes in IBD. Together, these findings reframe microbial MTX metabolism from passive drug detoxification to active regulation of host mitochondrial and inflammatory homeostasis.
Cho J, Danner R, Kim WS, Lopez L, Williams J, Singh A, Han JA, Van Vranken JG, Walker AS, Rhoads TW
Effects of low-dose atorvastatin combined with reduced-dose prednisolone in acetic acid-induced ulcerative colitis in rats. Immunologic research | 2026-11-05
Long-term corticosteroid treatment for ulcerative colitis (UC) is often limited by dose-dependent adverse effects, highlighting the need for strategies that reduce steroid exposure. This study evaluated the efficacy of a combination of half-doses of Atorvastatin and Prednisolone in rats with acetic acid-induced colitis. Thirty-five rats were allocated to five groups (n = 7 per group): normal control, vehicle-treated UC control, UC treated with atorvastatin (10 mg/kg/day, orally), UC treated with prednisolone (10 mg/kg/day, orally), and UC treated with the combination of atorvastatin (5 mg/kg/day) plus prednisolone (5 mg/kg/day), orally. Treatment continued for 10 days. Disease activity index (DAI), colonic edema index, histopathological leukocyte infiltration, pro-inflammatory cytokines, myeloperoxidase (MPO), malondialdehyde (MDA), nitric oxide (NO), and tissue levels of Nrf2, HO-1, and NF-kB were evaluated. Compared with untreated UC, all treatment groups showed attenuation of disease-associated changes. The half-dose combination was associated with the lowest cumulative DAI and day-10 DAI, markedly reduced leukocyte infiltration, and lower MPO and inflammatory cytokine levels than either monotherapy in several comparisons. It also normalized MDA and brought NF-kB levels toward those observed in healthy controls, while increasing Nrf2 and HO-1 levels. These findings indicate that low-dose atorvastatin combined with reduced-dose prednisolone can attenuate experimental colonic injury and inflammation more strongly than either monotherapy under the conditions tested.
Qaderi M, Abtahi Froushani SM
Guselkumab resolved refractory Crohn’s disease-associated peritendinous inflammation documented by serial ultrasonography and magnetic resonance imaging. Scandinavian journal of rheumatology | 2026-11-04
Letter on: ‘Impact of Prior Biologic Mechanism of Action on Anti-TNF Effectiveness in Inflammatory Bowel Disease: An ENEIDA Registry Study’. Authors’ Reply.Letter★ Alimentary pharmacology & therapeutics | 2026-11-04
Abstract not available.
Yagüe Caballero C, García-López S, Casas-Deza D
Letter on: ‘Impact of Prior Biologic Mechanism of Action on Anti-TNF Effectiveness in Inflammatory Bowel Disease: An ENEIDA Registry Study’.Letter★ Alimentary pharmacology & therapeutics | 2026-11-04
Abstract not available.
Tyagi B, Ratnakar PJ, Mantravadi HB, Nainwal P, Srinivasan H
Long-Term Follow-up of Azathioprine-Induced Portosinusoidal Vascular Disease in a Patient With Crohn’s Disease.Case report ACG case reports journal | 2026-11-04
Azathioprine is widely used to treat inflammatory bowel disease, organ transplantation, and autoimmune disorders. Hepatotoxicity is a rare but serious complication. We report a 48-year-old man with ileocolonic Crohn’s disease who developed azathioprine-induced portosinusoidal vascular disease (PSVD) after 15 years of treatment. Diagnosis was suspected due to persistent cytopenia (leukopenia and thrombocytopenia) and when transabdominal ultrasonography and upper gastrointestinal endoscopy showed signs of portal hypertension. There was also an extensive portal thrombosis in the right portal vein, portal bifurcation, and origin of the left portal vein. Liver biopsy confirmed PSVD, showing nodular regenerative hyperplasia, sinusoidal dilation, and obliterative portal venopathy without cirrhosis. Treatment included azathioprine discontinuation, carvedilol, and anticoagulants. After 4 years of follow-up, Crohn’s disease remained in deep remission, portal thrombosis recanalized, and portal hypertension stabilized. This case highlights the importance of monitoring for PSVD in long-term thiopurine users.
Azizi F, Ouldgougam R, Aouameur Y, Bourezak SES, Gasri M, Amir ZC, Boudjella MEA
Early decline in anti-integrin αvβ6 autoantibodies strongly predicts 1-year clinical remission in vedolizumab-treated patients with ulcerative colitis. eGastroenterology | 2026-11-02
Anti-integrin αvβ6 immunoglobulin G autoantibodies have emerged as one of the most accurate non-invasive biomarkers for ulcerative colitis (UC). We aimed to validate their diagnostic performance in a French multicentre cohort of patients with inflammatory bowel disease (IBD) and to evaluate their predictive value for vedolizumab clinical response. We performed a multicentre, non-interventional post hoc analysis using prospectively collected serum samples and clinical data from two parent prospective observational studies: VEDOPREDIRESP (patients with IBD initiating vedolizumab) and GOLILOR (patients with UC undergoing golimumab dose intensification). Serum anti-αvβ6 autoantibody titres were quantified by ELISA at baseline and week 6 (VEDOPREDIRESP) or week 8 (GOLILOR), blinded to clinical outcomes. The primary endpoint was sustained clinical remission at week 52. In the VEDOPREDIRESP cohort (n=115; 67 UC, 48 Crohn’s disease (CD), sustained clinical remission at week 52 was achieved in 54% of patients with UC. Baseline serum anti-αvβ6 autoantibody titres were significantly higher in UC than in CD (median 271 ng/mL (IQR 38-884) vs 5.2 ng/mL (2.5-10), p<0.001), with seropositivity (>9.1 ng/mL) in 94% vs 19%, respectively. Receiver operating characteristic (ROC) analysis confirmed excellent diagnostic performance to discriminate between UC and CD (area under the ROC curve (AUC) 0.93; optimal cut-off 15 ng/mL; sensitivity 92%, specificity 95%). In patients with UC treated with vedolizumab, titres declined significantly from baseline to week 6 (median 243 ng/mL (176-884) to 190 ng/mL (89-320), p=0.040). A >30% reduction at week 6 strongly predicted sustained remission at week 52 (AUC 0.79; sensitivity 78%, specificity 80%). Multivariable analysis identified this early decline as the only statistically significant independent predictor of 1-year remission (adjusted OR 5.36, 95% CI 1.12 to 8.54, p=0.040). Notably, in an independent cohort of 47 patients with UC undergoing golimumab dose intensification, there was no reduction in median serum anti-αvβ6 autoantibody levels, with levels remaining stable from 197 ng/mL at week 0 to 205 ng/mL (97-457) at week 8 (p=0.730). Anti-αvβ6 autoantibodies robustly discriminate UC from CD. In patients with UC treated with vedolizumab, their early and selective decline predicts clinical remission at 1 year and provides a precision tool to optimise gut-selective therapy in real time.
Roblin X, Mechi F, Berger AE, Fumery M, Nancey S, Hébuterne X, Carbonnel F, Altwegg R, Barrau M, Sparrow MP
[Impact of tumor necrosis factor superfamily member 4 gene polymorphisms on the risk of Crohn’s disease and clinical efficacy of ustekinumab]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics | 2026-11
To explore the impact of tumor necrosis factor superfamily member 4 (TNFSF4) gene polymorphisms on the risk and clinicopathological features of Crohn’s disease (CD), as well as the clinical efficacy of ustekinumab (UST). A total of 296 patients with CD diagnosed at the Department of Gastroenterology, The Second Affiliated Hospital of Wenzhou Medical University between January 2018 and August 2025, and 532 healthy controls were selected. Genotypes of TNFSF4 (rs3850641 and rs45454293) were detected using multiplex polymerase chain reaction-ligase detection reaction technique. According to the Montreal Classification Criteria of Crohn’s disease, the patients were divided into subgroups. The degree of clinical activity and intestinal inflammation degree of CD patients were evaluated by the Crohn’s disease activity index (CDAI) and Simplified Crohn’s disease endoscopic score (SES-CD), respectively. Unconditional Logistic regression model was used to analyze the distribution of TNFSF4 gene polymorphisms between the CD group and health control group, as well as between different subgroups of CD patients. Among them, a total of 247 cases receiving the routine UST therapy were divided into clinical response group (CDAI decreased by ≥ 100 points compared to week 0 or CDAI < 150 points) and clinical non-response group based on the changes in CDAI at week 8. They were also divided into mucosal healing group (SES-CD ≤ 2 points or no mucosal ulcer) and non-mucosal healing group based on the changes in SES-CD at week 34. Univariate Logistic regression was used to analyze the influencing factors for the clinical response and mucosal healing. Furthermore, unconditional Logistic regression was applied to assess the effect of TNFSF4 gene variants on the clinical response and mucosal healing. Generalized estimating equations were employed to analyze the effect of TNFSF4 gene polymorphisms on the longitudinal changes of efficacy outcomes. Bonferroni correction was applied for multiple comparisons. The variant genotype (AG+GG) and variant allele (G) of rs3850641 in the CD group were more frequent than those in the control group (38.18% vs. 29.32%, P = 0.011, adjusted P = 0.022; 21.45% vs. 16.45%, P = 0.015, adjusted P = 0.030). The same conclusion was also drawn for the variant genotype (CT+TT) and variant allele (T) of rs45454293 (35.81% vs. 27.26%, P = 0.012, adjusted P = 0.024; 19.59% vs. 14.76%, P = 0.014, adjusted P = 0.028). Although the homozygous variant genotype (TT) of rs45454293 was more frequent among patients with stricturing or penetrating CD compared with those with non-stricturing, non-penetrating CD (5.93% vs. 1.24%, P = 0.041), the adjusted P value was over 0.05 after Bonferroni multiple correction. At week 8 of the UST therapy, the homozygous variant genotype (GG) of rs3850641 in the response group was less prevalent compared with the non-response group (1.69% vs. 11.59%, P = 0.004, adjusted P = 0.008). Similar result was obtained for the homozygous variant genotype (TT) of rs45454293 (1.69% vs. 10.14%, P = 0.008, adjusted P = 0.016). At week 34, the homozygous variant genotype (GG) of rs3850641 in the mucosal healing group was less common compared with the mucosal non-healing group (1.27% vs. 10.11%, P = 0.015, adjusted P = 0.030). The rs3850641 and rs45454293 variants may not only increase the risk of CD, but also reduce the early clinical response rate of the UST therapy. The rs3850641 variant may also lower the late mucosal healing rate of the UST therapy.
Li N, Xiong Y, Zhu X, Hu D, Ma G, Xu Y, Jiang Y
DOI: 10.3760/cma.j.cn511374-20260115-00020 | View on PubMed →
Anti-TNF Therapy Is Associated With Browning- and Immune-Related Changes in Creeping Fat in Crohn’s Disease.Observational study★ United European gastroenterology journal | 2026-11
Creeping fat (CrF) in Crohn’s disease (CD) is a metabolically active perilesional adipose tissue involved in intestinal inflammation. Whether biological therapies modify its browning-associated phenotype remains largely unexplored. We investigated whether anti-TNF treatment is associated with changes in browning-, mitochondrial biogenesis- and immune-related pathways in CrF and whether similar molecular changes occur following ex vivo infliximab exposure. Two independent human cohorts were analysed. (1) Observational cohort: CrF biopsies from anti-TNF-treated and anti-TNF-naïve CD patients (n = 14 and n = 19, respectively) were analysed for metabolic and inflammatory gene and protein expression. AdMSCs and mature CrF-derived adipocytes were isolated, and UCP1 protein abundance was assessed by immunohistochemistry and western blotting. (2) Ex vivo cohort: Paired CrF explants from anti-TNF-naïve patients with CD undergoing surgery were cultured with or without infliximab (5 mg/kg-equivalent, 24 h) and analysed by RT-qPCR and immunohistochemistry. Anti-TNF-treated patients showed higher UCP1 expression in CrF at mRNA and protein levels. CrF-derived mature adipocytes from treated patients exhibited increased expression of browning-/thermogenesis- and mitochondrial biogenesis-associated genes, together with reduced selected pro-inflammatory markers. AdMSCs also showed exploratory differences in their conditioned-medium protein profile, although no protein remained significant after FDR correction. Ex vivo infliximab exposure was associated with changes in selected browning-, mitochondrial biogenesis- and immune-related markers. Together, the observational and ex vivo findings identify CrF as an anti-TNF-responsive immunometabolic compartment in CD, characterised by coordinated browning-, mitochondrial biogenesis- and immune-related molecular changes. Functional studies are needed to establish the metabolic significance of these changes.
Monfort-Ferré D, Ginés I, Cepero C, Cabré L, Caro A, Menacho M, Gené M, Garcia M, Lahoz MDC, Mañas MJ
Comparative effectiveness of IL-12/23 and IL-23 inhibitors versus JAK inhibitors in patients with inflammatory bowel disease and hidradenitis suppurativa: a real-world propensity-matched analysis. Crohn’s & colitis 360 | 2026-10-30
Inflammatory bowel disease (IBD) and hidradenitis suppurativa (HS) frequently coexist and share overlapping immune pathways, yet comparative real-world outcomes between IL-12/23 or IL-23 inhibitors and Janus kinase (JAK) inhibitors in this population remain poorly defined. We conducted a retrospective cohort study using a large, multicenter, real-world dataset. Adults (≥16 years) with IBD and HS who initiated an IL-12/23 or IL-23 inhibitor after anti-TNF therapy or a JAK inhibitor were included; patients with prior exposure to the opposing drug class were excluded. Propensity score matching (1:1) yielded 150 patients per cohort. Outcomes from 30-365 days included acute care utilization, corticosteroid use, IBD complications, and overall and hidradenitis-specific antibiotic use. After propensity score matching, 300 patients were included (150 per cohort; mean age 38 years; 75.3% female). Rates of emergency department visits or hospitalization were similar between groups (RR 1.20, 95% CI, 0.82-1.77). Corticosteroid use risk was numerically higher in the IL-12/23 or IL-23 cohort (RR 1.20, 95% CI, 0.98-1.46). IBD-related complications did not differ significantly (RR 1.06, 95% CI, 0.58-1.93). Overall antibiotic use was comparable, while hidradenitis-specific antibiotic use was higher in the IL-12/23 or IL-23 cohort (RR 1.47, 95% CI, 1.11-1.95). In this real-world analysis, IL-12/23 or IL-23 inhibitor therapy was associated with higher hidradenitis-specific antibiotic use and numerically greater but statistically nonsignificant corticosteroid exposure, while hospitalization and IBD-related complications were comparable. These findings should be interpreted cautiously given the absence of validated disease-activity measures; prospective studies are needed to inform optimal therapeutic selection.
Hafez Y, Osman A, Syn WK, Shmais M
Real-world success of de-escalating upadacitinib induction dosing in ulcerative colitis is predicted by steroid-free clinical and biochemical remission, not induction duration. Crohn’s & colitis 360 | 2026-10-29
Data guiding upadacitinib dose de-escalation in ulcerative colitis (UC) are limited. We evaluated factors associated with UC-related complications (UCRC) after upadacitinib was reduced from 45 mg daily. This retrospective study included adults with UC at a tertiary center who underwent upadacitinib de-escalation (4/2022-11/2025). The primary outcome was a 12-month composite of UCRC (upadacitinib re-escalation or discontinuation, new systemic steroids, new advanced therapy, hospitalization, or colectomy). Predictors of UCRC after de-escalation were assessed using Cox proportional hazards modeling, including steroid-free clinical remission (SFCR), defined as a stool frequency subscore of 0 or 1 and a rectal bleeding subscore of 0 without systemic steroid use, and biochemical remission, defined as a fecal calprotectin (FC) < 150 μg/g or a C-reactive protein (CRP) < 5 mg/L when FC was unavailable. Optimal CRP and FC cut points were identified via ROC curves. Among 70 patients, 25 (35.7%) experienced UCRC (median follow-up 56 weeks). Induction duration, prior advanced therapy exposure, and endoscopic severity did not differ significantly between those with and without UCRC. Patients without UCRC were more likely to have achieved SFCR (51.1% vs 20.0%, P=.01) and biochemical remission (53.3% vs 28.0%, P=.04) prior to de-escalation, with lower median CRP (0.8 vs 1.5 mg/L, P=.04) and FC (79.5 vs 208.0 μg/g, P=.03). In multivariable analysis, achieving SFCR (aHR 0.33, 95% CI, 0.12-0.91) and biochemical remission (aHR 0.34, 95% CI, 0.13-0.85) independently predicted lower UCRC risk, and achieving both conferred additional UCAE-free survival benefit. Optimal cut points predicting UCRC were CRP > 12.7 mg/L (sensitivity 40%, specificity 93%) and FC > 58.7 μg/g (sensitivity 100%, specificity 47%). SFCR and biochemical remission prior to upadacitinib de-escalation, but not induction duration, predict lower UCRC risk. Upadacitinib de-escalation should be guided by response assessment rather than a predetermined induction duration.
Dalal RM, Rotondo-Trivette S, Mason AR, Leveille L, Yin J, Missi C, Boktor M, Fudman DI
Baseline mucosal transcriptomic endotypes stratify healing capacity and biologic therapy outcomes in ulcerative colitis: an integrative multi-cohort study. Frontiers in pharmacology | 2026-10-23
Numerous baseline mucosal transcriptomic signatures have been proposed to stratify therapeutic outcomes in ulcerative colitis (UC), but cross-cohort transferability is frequently undermined by platform heterogeneity, endpoint/timepoint differences, and drug-specific biases. The resulting lack of a biologic-agnostic molecular baseline has limited clinical translation and prospective trial design. We integratively re-analyzed endpoint-linked baseline mucosal transcriptomes from seven public UC GEO series (778 unique baseline samples), with three additional public accessions used for disease-activity and contextual analyses. The primary response/healing synthesis used five study slices spanning anti-TNF, anti-integrin, and etrolizumab-treated cohorts. Unsupervised decomposition identified baseline endotypes, and endotype-outcome associations were estimated within each cohort (OR per 1-SD increase) and summarized by random-effects cross-cohort pooling with heterogeneity reporting, rank/seed sensitivity analyses, endpoint-restricted summaries, and negative controls. Across five primary response/healing study slices, an epithelial barrier endotype (EPITHELIAL_BARRIER/NMF_C3) was associated with higher odds of response/healing (random-effects cross-cohort pooling OR = 3.171, 95% CI 1.491-6.744), whereas macrophage-inflammation and lymphoid/complement-stromal axes (MACROPHAGE_INFLAMMATION/NMF_C1 and LYMPHOID_COMPLEMENT_STROMAL/NMF_C2) were associated with lower odds of response/healing (OR = 0.359, 0.175-0.735; OR = 0.378, 0.220-0.651). The epithelial estimate was largest in GSE73661 but remained significant in the five-study leave-one-out summary after excluding that cohort (OR = 2.547, 95% CI 1.271-5.105). Cross-mechanism evaluation included UNIFI ustekinumab week-8 mucosal healing (UST arm n = 358; EPITHELIAL_BARRIER OR = 4.483, 2.263-8.881) and directionally consistent effects in etrolizumab. Endotype axes were supported by independent single-cell localization (FDR = 0.0026). Treatment-interaction tests were imprecise and did not establish drug-class-specific prediction. In cohort-heldout prediction, AUC ranged from 0.717 to 0.758, but calibration was variable. A network-based therapeutic prioritization was enriched for UC-approved agents (AUC = 0.741; permutation p = 6.0 × 10- 4) and is presented as hypothesis-generating. Baseline mucosal endotypes stratify healing capacity and therapeutic outcomes across public cohorts, with orthogonal support from single-cell localization. These findings support prospective evaluation as biologic-agnostic outcome stratifiers rather than established drug-specific predictive biomarkers.
Chen W, Zeng S
Microbiome & Immunology (19 papers)
Dsg2 truncation causes a severe intestinal epithelial barrier breakdown and alters microbiome and immune response. JCI insight | 2026-11-10
Inflammatory bowel diseases (IBD) including Crohn’s disease (CD) are characterized by impaired intestinal epithelial barrier (IEB) function. Alterations in the desmosomal cadherin desmoglein 2 (Dsg2) have been linked to loss of IEB and intestinal inflammation in IBD. We investigated the pathogenic impact of a cytoplasmatic-truncating mutation in the desmosomal cadherin desmoglein 2 gene (DSG2) in an IBD patient. Genetic analysis of a CD patient revealed a likely pathogenic DSG2 mutation leading to a truncated protein lacking part of the intracellular domain. Generation of an enterocyte-specific mouse model to recapitulate the human mutation resulted in a lethal intestinal barrier defect which was evident in homozygous but not in heterozygous mice. In vitro, barrier defects correlated with changes in Dsg2 mobility and upregulation of pore-forming tight junction protein claudin-2. Organoids derived from heterozygous Dsg2 truncated mice exhibited increased epithelial susceptibility to proinflammatory cytokines. Bulk RNAseq followed by gene ontology analysis in homozygous mice revealed a skewed IL17/IL23 response overlapping with transcriptional changes in patients with CD. Furthermore, 16S rRNA sequencing revealed alterations in microbiome composition in animals that carried the Dsg2 truncation. In summary, a patient-derived mutation in the DSG2 gene causing cytoplasmic truncation in homozygous state induced a lethal intestinal barrier breakdown in mice paralleled by altered gut microbiota and intestinal immune response.
Kugelmann D, García-Ponce A, Thielemann N, Radeva MY, Anders M, Kang DE, Siadjeu C, Burkard N, Horn AK, Neubauer J
Microbiome changes following immigration: Rethinking “Westernization” as an explanatory concept.Review★ Gut microbes | 2026-11-10
An emerging focus in microbiome science is on changes to people’s microbiomes following immigration, particularly to so-called Western countries, such as the USA, Canada, and Australia. Moving to these regions has been linked to microbiome changes that may increase immigrants’ susceptibility to health problems, including obesity and Inflammatory Bowel Disease. The term “Westernization” (and adjacent terminology) is frequently used to describe changes in diet, lifestyle, and built environment - and the consequent microbiome shifts - associated with immigration. However, what Westernization means in this context, and whether it is an appropriate descriptor, is often unclear. The purpose of this article is to provide a review of the diverse meanings associated with the terms “West”, “Western”, “Westernization” (and similar) across microbiome-related research and broader uses. We argue that these terms can obscure the specific structural, environmental, and cultural factors shaping microbiome changes. We discuss the consequences of this imprecision and provide recommendations for future research. Avoiding oversimplified conclusions about what impacts immigrants’ microbiome and health can contribute to more accurate targets for public health interventions for these groups in the long term.
Sharma R, Holcomb LE, Ishaq SL, O’Doherty KC
The Microbiota-Metabolism Axis: Mechanistic Insights and Translational Targets Across Diabetes and Gastrointestinal Disorders.Review International journal of endocrinology | 2026-11-09
The gut microbiota (GM) modulates host energy balance, glucose-lipid metabolism, and enteroendocrine signaling through metabolite-receptor axes that include short-chain fatty acids (SCFAs) acting on FFAR2/FFAR3 (GPR43/GPR41), microbially transformed bile acids signaling via FXR/TGR5, and amino-acid/choline-derived compounds such as imidazole propionate (ImP) and trimethylamine N-oxide (TMAO). These pathways regulate incretin biology (GLP-1/PYY), insulin sensitivity, hepatic glucose output, adipose lipolysis, and appetite, thereby shaping risk and progression of Type 2 diabetes mellitus (T2DM), obesity, inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and related conditions. Here, we synthesize mechanistic and translational evidence, highlight bidirectional drug-microbiome interactions (GLP-1 receptor agonists), and review interventions spanning diet, pre/probiotics, fecal microbiota transplantation (FMT), and pharmacologic targeting of bile-acid and SCFA pathways. Together, these findings support precision strategies that profile GM-metabolite signatures (e.g., SCFAs, secondary bile acids, and ImP TMAO) to guide prevention and therapy in metabolic and gastrointestinal disease.
Akif A, Sultana N, Mikrani I
A homogeneous acidic polysaccharide from Guangxi-cultivated Alpiniae Oxyphyllae fructus attenuates DSS-induced ulcerative colitis by remodeling the amino acid metabolism-microbiota-barrier axis.★ International journal of biological macromolecules | 2026-11-06
Ulcerative colitis (UC) is a chronic intestinal inflammatory condition with limited management options, driving interest in food-derived bioactive polysaccharides as potential dietary interventions. Alpiniae Oxyphyllae Fructus (AOF), an edible and medicinal plant traditionally used for gastrointestinal health, is widely cultivated in Guangxi, China; however, polysaccharides from Guangxi-grown AOF have not been systematically characterized, and their structure-activity relationships in UC remain undefined. In this study, a homogeneous acidic polysaccharide (AOFP-3) was isolated from Guangxi-cultivated AOF and structurally characterized. Its anti-UC activity was evaluated in a dextran sulfate sodium (DSS)-induced mouse model by integrating untargeted metabolomics, targeted amino acid profiling, 16S rRNA sequencing, and immunohistochemistry. AOFP-3 was identified as a highly branched acidic heteropolysaccharide (Mw 19.728 kDa) rich in galacturonic acid (53.38%), with a putative backbone of alternating →4)-α-D-GalpA-(1 → and →4)-α-D-GalpA-6-OMe-(1 → residues. In DSS-induced UC mice, AOFP-3 dose-dependently alleviated weight loss, colon shortening, histopathological damage, and inflammation. Mechanistically, AOFP-3 treatment was associated with restoration of amino acid homeostasis, particularly involving branched-chain amino acids and the alanine/glycine-serine-threonine metabolic axis, with remodeling of the gut microbiota (enrichment of Akkermansia and Lactobacillus and suppression of Staphylococcus and Enterococcus) and repair of both physical (Occludin, Claudin-1, ZO-1) and chemical (MUC-2, goblet cells) barriers. These findings establish a structural and mechanistic basis for the bioactivity of Guangxi-grown AOF polysaccharides and support their further investigation as functional food ingredients for gut health promotion.
Xiang Y, He C, Yuan H, Wang E, Yan Z, Li Z, Liu C, Zhang Y, He J
Fecal neuraminidase correlates with inflammatory signatures and microbiome shifts in preclinical Crohn’s disease.★ Gut microbes | 2026-11-05
The mucus layer, rich in mucin glycoproteins, serves as a critical barrier to microbial invasion. Neuraminidases cleave terminal sialic acids from mucin glycans, a process that may influence mucus integrity, epithelial exposure to microbial antigens, and mucosal immune responses, making fecal neuraminidase activity a biologically relevant functional readout of host-microbe interactions in the context of Crohn’s disease (CD) pathogenesis. We evaluated whether fecal neuraminidase activity is associated with future CD risk and examine its relationships with inflammatory and microbial signatures relevant to early disease development. Within the prospective GEM cohort, 69 individuals who later developed CD were matched to 69 healthy first-degree relative controls. Fecal neuraminidase activity was measured using a fluorometric assay. Conditional logistic regression assessed its association with future CD risk. Partial Spearman correlations evaluated relationships with 446 serum proteins (OLINK), followed by pathway enrichment analysis, and with fecal calprotectin (FCP) and gut microbial composition (16S rRNA sequencing). Fecal neuraminidase activity was positively associated with future CD (OR = 1.541; 95% CI: 1.05-2.25; p = 0.026). Proteins correlated with neuraminidase activity were enriched in immune and inflammatory pathways. Neuraminidase activity was positively correlated positively with FCP (p ≤ 0.05), and its association with future CD was attenuated after adjustment for FCP. Fourteen microbial taxa were significantly correlated with neuraminidase activity (q ≤ 0.05). Fecal neuraminidase activity’s relationships with inflammatory markers and microbial taxa support its potential relevance as a functional marker of host-microbe alterations during preclinical CD.
Mu K, Dang CP, Xue M, Li Q, Huynh HQ, Griffiths AM, Turner D, Moayyedi P, Steinhart AH, Dieleman LA
Mucosal transcriptomic and fecal microbiome signatures associated with persistent symptoms in quiescent Crohn’s disease.★ Inflammatory bowel diseases | 2026-11-05
Persistent symptoms in quiescent Crohn’s disease (qCD + S) lack clear mechanistic explanations. Building on prior evidence linking qCD + S to sulfidogenic microbial metabolism, this study characterizes the underlying site-specific mucosal transcriptional programs and host-microbe interactions associated with qCD + S. We integrated paired metagenomic and transcriptomic data from a cross-sectional cohort of patients with qCD. Host-microbe interactions in the ileum and rectosigmoid colon were analyzed using differential expression, penalized regression, and sparse canonical correlation analysis. qCD + S was associated with transcriptional differences in separate analyses of ileal and rectosigmoid samples. The ileum showed reduced expression of genes related to immune surveillance, whereas the rectosigmoid colon exhibited reduced chemokine-related and increased ribosomal gene expression. Multi-omic integration identified associations between previously identified sulfidogenic microbes and mucosal genes related to mitochondrial metabolism, epithelial homeostasis, and neurosensory signaling. Exploratory sparse canonical correlation analysis identified multivariate patterns involving oral-associated taxa and mucosal genes related to B-cell receptor signaling and RNA-processing. Persistent symptoms in qCD are mucosal transcriptional differences and fecal microbial features. These findings suggest a model in which altered immune regulation, microbial sulfur metabolism, and downstream epithelial and metabolic stress pathways contribute to symptom persistence despite quiescent inflammation, but this model requires mechanistic validation.
Guo K, Golob J, Berinstein J, Sheehan J, Chey WD, Higgins PDR, Young V, Rao K, Singh P, Bishu S
Lactobacillus Plantarum-Derived Extracellular Vesicles Alleviate DSS-Induced Colitis and Modulate Autophagy-Related Markers. Probiotics and antimicrobial proteins | 2026-11-05
Inflammatory bowel disease (IBD) encompasses a group of chronic inflammatory disorders of the intestine, which have been associated with a rising global incidence. Autophagy plays a crucial anti-inflammatory role in the context of intestinal inflammation. This study was designed to investigate the protective effects of Lactobacillus plantarum-derived extracellular vesicles (LpEVs) against dextran sodium sulfate (DSS)-induced colitis in mice and to elucidate the underlying mechanisms associated with autophagy. In this study, mouse intestinal epithelial cells (MODE-K) were pre-incubated with LpEVs and subsequently stimulated with lipopolysaccharide (LPS) to establish an inflammatory model. Our findings indicate that LpEVs can inhibit LPS-induced inflammation. Additionally, we explored the potential effects of LpEVs in alleviating DSS-induced colitis. C57BL/6 mice received LpEVs at a dose of 1 µg/g body weight by oral gavage before the induction of colitis with DSS. The results demonstrated that LpEVs significantly alleviated the severity of DSS-induced colitis. Furthermore, LpEVs exert anti-inflammatory activities, which are accompanied by alterations in autophagy-related markers and reduced NLRP3 expression, contributing to the alleviation of intestinal inflammation. These findings support the potential application of LpEVs for colitis intervention, thereby laying a scientific foundation for Lactobacillus-derived therapeutic strategies against colitis.
Zhang X, Ji X, Shan X, Wang A, Liu M, Zhang S, Qu G, Yin Y, Wang C, Hu J
Bile acid dysmetabolism and microbial dysbiosis coincide with Clostridioides difficile infection in pediatric inflammatory bowel disease.Review Npj gut and liver | 2026-11-05
Pediatric inflammatory bowel disease (IBD) patients are at increased risk for Clostridioides difficile infection. This review highlights bile acid dysmetabolism, driven by gut microbiota dysbiosis and reduced microbial production of secondary bile acids, as a key factor linking pediatric IBD to increased CDI susceptibility. We examine interactions among IBD, dysbiosis, bile acid metabolism, and C. difficile, and discuss emerging microbiome-based interventions aimed at restoring bile acid homeostasis.
Rowe JC, Winston JA
Multi-matrix metabolome and microbiome profiling in diarrhea-predominant irritable bowel syndrome and ulcerative colitis in remission with IBS-like symptoms.★ Inflammatory bowel diseases | 2026-11-04
Irritable bowel syndrome (IBS)-like symptoms frequently persist in patients with ulcerative colitis (UC) in remission. Whether UC in remission with IBS-like symptoms (UCR-IBS) represents functional overlap with diarrhea-predominant IBS (IBS-D) or a distinct metabolic phenotype remains unclear. In this exploratory cross-sectional study, 39 patients with IBS-D, 21 with UCR-IBS, and 35 healthy controls were enrolled. Serum, urine, fecal, and colonic mucosal samples were collected. Untargeted metabolomics, targeted tryptophan profiling, fecal 16S ribosomal RNA gene sequencing, predicted microbial functional profiling, and microbe-metabolite association analyses were performed. Tryptophan-related metabolism was altered in both patient groups, but the patterns differed across biological matrices. Compared with IBS-D, UCR-IBS showed higher serum N-formylkynurenine (NFK) concentrations, and fecal findings suggested reduced concentrations of microbiota-associated indole metabolites. Microbiome differences were modest, but predicted nicotinate/nicotinamide metabolism was enriched in UCR-IBS. Exploratory network analysis identified associations between tryptophan-related metabolites and selected bacterial genera in each group. Multi-matrix profiling shows tryptophan-related metabolic differences between mesalazine-treated UCR-IBS and IBS-D, highlighting higher serum NFK concentrations in UCR-IBS. These findings provide a basis for investigating host-microbiota metabolic relationships across systemic and intestinal compartments during UC remission.This trial was registered in the Chinese Clinical Trial Registry (ChiCTR; https://www.chictr.org.cn/) under registration number ChiCTR2200060224.
Chen G, Du S, Li H, Wang H, Zhu H, Zhang Q, Yang R, Wu X, Shao B, Zhang Y
Microalgae and zinc-polyphenol networks functionalized alginate oral microspheres for synergistic treatment of inflammatory bowel disease. Biomaterials advances | 2026-11-02
Inflammatory bowel disease (IBD) is characterized by intestinal barrier disruption, oxidative stress, and dysregulated gut microbiota. Current therapies often fail to address these multifactorial pathologies simultaneously. Here, a hierarchical oral microsphere system, SP@QZnNPs@SA, was developed by integrating Spirulina platensis (SP) as a mucoadhesive carrier with quercetin-Zn2+ networks (QZnNPs) and a pH-responsive alginate shell for colon-targeted release. SP provides prolonged colonic retention and prebiotic activity, while QZnNPs synergistically alleviate oxidative stress and support epithelial barrier repair. The alginate shell protects the payload during gastrointestinal transit and enables controlled release in the inflamed colon. In vitro studies demonstrated effective ROS scavenging and promotion of macrophage polarization toward an anti-inflammatory phenotype. Oral administration in the colitis model led to alleviation of disease symptoms, reinforcement of epithelial barrier function, and beneficial reorganization of gut microbial composition. SP@QZnNPs@SA outperformed individual components, highlighting the synergistic effects of the hierarchical design. The study provides a translatable strategy for oral therapeutics targeting complex gastrointestinal disorders and offers a design blueprint for integrating living microalgal carriers with multifunctional nanoparticles.
Du Y, Zhou Z, Ouyang XK, Wang N
Caffeic acid regulates the gut microbiota-tryptophan metabolic axis to improve intestinal barrier function and relieve ulcerative colitis.★ Phytomedicine : international journal of phytotherapy and phytopharmacology | 2026-11-01
Ulcerative colitis (UC) is a chronic inflammatory bowel disease for which current therapies remain inadequate. Caffeic acid (CA), a natural hydroxycinnamic acid polyphenol, possesses anti-inflammatory and antioxidant properties. However, whether CA engages the gut microbiota-tryptophan-aryl hydrocarbon receptor (AHR)-Nrf2 axis in UC has not been established. To evaluate the anti-UC activity of CA in vivo and in vitro and to elucidate its underlying mechanisms through a multi-platform integrative strategy. A dextran sulfate sodium (DSS)-induced murine colitis model and lipopolysaccharide (LPS)-stimulated mouse colonic epithelial cells (MCECs) were used in parallel. Mechanism was addressed by combining microbiota, metabolomic, transcriptomic and proteomic profiling with faecal microbiota transplantation, computational and biophysical target validation, and siRNA-mediated AHR knockdown. CA was administered at 10 and 20 mg/kg/day, with 5-aminosalicylic acid as positive control. Complementary platforms included 16S rRNA gut microbiota sequencing, untargeted serum metabolomics, colonic transcriptomic profiling, data-independent acquisition mass spectrometry proteomics, human UC single-cell RNA sequencing (GEO: GSE214695), faecal microbiota transplantation into antibiotic-pretreated recipients, molecular docking, 100 ns molecular dynamics simulation, cellular thermal shift assay, dual-luciferase reporter assay, and co-immunoprecipitation. CA dose-dependently alleviated dextran sulfate sodium-induced colitis, suppressed NF-κB activation, and reduced interleukin-6, interleukin-1β, and tumour necrosis factor alpha. Gut microbiota profiling revealed enrichment of Bifidobacterium and Dubosiella with depletion of Escherichia-Shigella. Transplantation of the CA-remodelled microbiota into antibiotic-pretreated recipients reproduced the protective phenotype and restored colonic AHR and cytochrome P450 1A1 expression, demonstrating that the remodelled community is sufficient to confer protection. Metabolomics showed enrichment of serotonin-branch tryptophan metabolites, with 5-hydroxytryptamine among the most significantly enriched differential metabolites. Molecular docking and 100 ns molecular dynamics simulation indicated stable binding of CA within the AHR ligand-binding domain, cellular thermal shift assay confirmed intracellular target engagement, and a dual-luciferase reporter assay demonstrated concentration-dependent activation of dioxin response element-driven transcription, establishing CA as an AHR agonist. CA increased Nrf2, NQO1 and HO-1 and restored Claudin-1, Occludin and zonula occludens-1; AHR knockdown reduced these effects and the suppression of NF-κB, indicating that both actions depend on AHR. CA ameliorates UC through convergent AHR activation, arising from both microbiota-mediated tryptophan reprogramming and direct receptor binding, with AHR-dependent Nrf2/NQO1/HO-1 induction and NF-κB suppression to restore intestinal barrier integrity. These findings support CA as a multi-target phytochemical candidate for UC treatment.
Lin X, Alioui Y, Wang W, Wu L, Ao J, Yan C, Liao J, Wang Z, Wu Y, Feng Y
Synbiotic of 2’-FL and B. longum subsp. infantis BXY2 Alleviates Colitis in Toddler Microbiota-Associated Mice: Potential Involvement of Gut Microbial Arachidonic Acid Metabolism. Journal of agricultural and food chemistry | 2026-11
Increasing inflammatory bowel disease (IBD) incidence in toddlers requires safe interventions. We developed a synbiotic combining 2’-fucosyllactose (2’-FL) with Bifidobacterium strain and evaluated its protective efficacy against DSS-induced colitis in toddler microbiota-associated (TMA) mice. Among 30 Bifidobacterium strains, Bifidobacterium longum subsp. infantis BXY2 and Bifidobacterium. breve BG4 utilized 2’-FL in vitro. However, only the 2’-FL and BXY2 synbiotic significantly alleviated colitis. The 400 mg/kg 2’-FL and BXY2 synbiotic showed the greatest protective effect, restoring body weight and colon length, reducing disease activity and histological scores, improving barrier function, attenuating inflammation. Compared with 2’-FL or BXY2 alone, the synbiotic enhanced goblet cells and barrier proteins. Metagenomics revealed enrichment of B. longum subsp. infantis and Phascolarctobacterium faecium. Metabolomics showed reduced fecal arachidonic acid (AA). These results indicated that gut microbial AA metabolism might be involved in alleviating colitis in TMA mice. Thus, this synbiotic is a promising preventive strategy for toddler IBD.
Jing Y, Bai X, Li J, Feng X, Gu Y, Ji Y, Zhai Z, Hao Y
Targeted Dual-Responsive Probiotic Microspheres for Sequential Protection, Adhesion, and On-Demand Release in Ulcerative Colitis Therapy. Biomacromolecules | 2026-11
Oral probiotics show promise for inflammatory bowel disease but are limited by poor gastrointestinal viability, targeting, and colonization. We developed a multi-targeting probiotic composite microsphere (PCM) via scalable solution blow-spinning, with >20-fold higher throughput than electrospinning. PCMs provide three key functions: (1) pH-triggered probiotic protection: PCMs contract in gastric acid, shielding probiotics and increasing survival 2162-fold over free probiotics; (2) charge-mediated adhesion: negatively charged microspheres adhere to positively charged mucin overexpressed at inflamed colonic lesions; and (3) enzyme-triggered release: overexpressed hyaluronidase degrades hyaluronic acid, releasing viable bacteria via the “Trojan horse” mechanism. This sequential mechanism ensures high local probiotic density at inflamed sites. In DSS-induced mouse colitis, PCMs outperformed 5-aminosalicylic acid in alleviating inflammation, repairing the mucosal barrier, and restoring microbial homeostasis. 16S rRNA sequencing showed selective enrichment of beneficial genera and suppression of inflammation-associated pathobionts. This scalable, multi-responsive platform offers next-generation oral therapy for IBD and microbiome-associated gastrointestinal diseases.
Liu S, Chen W, Chen L, Wang Y, Zhou L, Yin Q, Wang Z, Wang D, Lu Z
Dynamic alterations in stool microbiota composition following faecal transplantation in patients with inflammatory bowel disease. Clinical and translational medicine | 2026-11
Abstract not available.
Olekhnovich EI, Kalachnyuk TN, Zhgun ES, Ivanov AB, Fedorov DE, Klimina KM, Veselovsky VA, Boldyreva DI, Larin AK, Matorin RI
Gut Microbiota-Derived β-Glucuronidase Governs the Anticolitic Efficacy of Daidzein via the ERβ-PI3K/Akt/mTOR-Autophagy Axis. Journal of agricultural and food chemistry | 2026-11
Precision nutritional interventions targeting the gut microenvironment have emerged as a pivotal strategy for managing inflammatory bowel disease (IBD). However, the specific microbial mechanisms governing the therapeutic efficacy of dietary flavonoids, such as daidzein (DA), remain largely unexplored. In this study, it was observed that administration of 40 mg/kg DA significantly attenuated DSS-induced colitis, preserving mucosal barrier integrity and suppressing inflammation. Multiomics analysis revealed that DA reprogrammed the gut microbiota composition, specifically enriching β-glucuronidase (GUS)-producing bacteria, especially Bacteroides thetaiotaomicron. Mechanistically, the effects of microbially bioactivated DA were associated with host estrogen receptor beta (ERβ) signaling. Pharmacological blockade further supported the involvement of ERβ signaling in the suppression of PI3K/Akt/mTOR signaling and restoration of autophagy, thereby contributing to intestinal epithelial repair. Collectively, these findings unveil a potential Microbiota-GUS-ERβ-PI3K/Akt/mTOR-autophagy mechanistic axis, establishing a robust theoretical foundation for precision nutritional strategies targeting specific gut microbiota.
Ding S, Chen Y, Li J, Liu G, He X, Fang J
Microbes and TNF drive colitis in the absence of innate lymphoid cells. iScience | 2026-10-27
Innate lymphoid cells (ILCs) are critical sources of cytokines necessary for intestinal homeostasis in immunocompetent conditions, yet their necessity in innate colitis remains unclear. Using a model of inflammatory bowel disease (IBD) in mice lacking adaptive immunity, we investigated whether ILCs are required for innate colitis. Interleukin-15 receptor alpha-deficient mice lacked intestinal ILC1 and natural killer (NK) cells, but innate colitis in these mice was not diminished. Deletion of IL-2 receptor gamma chain, which ablates all ILCs and NK cells, also did not prevent innate colitis. Antibiotic treatment of mice lacking all ILCs prevented colitis. Similarly, TNF deficiency prevented colitis in the absence of all ILCs, demonstrating that TNF is essential for microbe-driven innate colitis in the absence of ILCs. These findings reveal that ILCs are redundant for innate colitis. Studies of innate colitis in the absence of ILCs may help understand mechanisms underlying IBD and the effectiveness of anti-TNF therapies.
Torres-Huerta A, Rajashekara AM, Mayer LC, Ruley-Haase K, Hiller M, Boger-May A, Reed T, Frech M, Bixby E, Elliot K
Th17 suppression strategies: targeting IL-17 and RORγt pathways in autoimmune diseases.Review Frontiers in immunology | 2026-10-27
T helper 17 (Th17) cells and their key effector cytokine, particularly IL-17A and IL-17F, play central roles in host defense against extracellular pathogens. However, they are also critically involved in the pathogenesis of many autoimmune and inflammatory diseases. Th17 cell differentiation, stabilization, plasticity, and pathogenicity are regulated by a network of cytokines and transcription factors, including IL-6, TGF-β, IL-23, STAT3, and the key transcription factor RORγt. RORγt-dependent pathways are also relevant to other immune populations, including group 3 innate lymphoid cells (ILC3s), highlighting the complexity of the IL-17 axis across tissues. Dysregulation of these pathways can lead to chronic inflammation and tissue damage in diseases such as psoriasis, rheumatoid arthritis, multiple sclerosis, and inflammatory bowel disease. Therapeutic targeting of the Th17 axis has led to clinically established approaches, particularly direct blockade of IL-17 signaling and inhibition of IL-23, whereas direct RORγt inhibition remains an investigational strategy. RORγt inhibitors may modulate Th17 differentiation and broader RORγt-dependent transcriptional programs, but their clinical development has been challenged by variable efficacy, safety considerations, and translational limitations. This review provides a comprehensive overview of Th17 biology, focusing on differentiation, plasticity, tissue-specific functions, and the contribution of Th17 and other RORγt-expression populations to autoimmune diseases. Furthermore, it critically compares established IL-17-targeted therapies with emerging RORγt inhibitors, emphasizing their distinct mechanisms, cellular and molecular targets, clinical evidence, safety, and developmental status. Finally, we discuss combination strategies, translational challenges, and emerging biomarkers that may contribute to more individualized therapeutic approaches and patient stratification.
Zian Z, Aliyu M, Hossain F, Zohora FT, Ceylan A, Ben Moussa N, Hsieh WJ, Abbes F, Abubakar SD, Azizi G
Dietary fiber, gut microbiota, and host immunity: the immunomodulatory roles of short-chain fatty acids.Review Frontiers in nutrition | 2026-10-23
Short-chain fatty acids (SCFAs) are a class of key metabolites produced by the gut microbiota through the fermentation of indigestible components such as dietary fiber. They primarily include acetate, propionate, and butyrate. In recent years, a large body of research has revealed that SCFAs are not only an important energy source for colonic epithelial cells but also key signaling molecules linking the gut microbiota to the host immune system. SCFAs play a central role in immune regulation. This review summarizes the production and characteristics of SCFAs. It explores the multifaceted roles of SCFAs in regulating immune homeostasis and inflammatory responses. Through key mechanisms such as activation of G protein-coupled receptors (GPCRs), inhibition of histone deacetylases (HDACs), and metabolic reprogramming, SCFAs broadly regulate the differentiation, function, and inflammatory responses of immune cells, maintain intestinal barrier integrity, and induce an anti-inflammatory state. At the same time, the manuscript analyzes the molecular mechanisms by which SCFAs contribute to inflammatory bowel disease, metabolic disorders, tumor immunity, and neuro-immune diseases through multi-organ pathways such as the “gut-liver axis” and the “gut-brain axis”. In addition, this article summarizes treatment strategies targeting SCFAs, including dietary interventions, probiotics, prebiotics, and fecal microbiota transplantation. It also discusses the current challenges in this field and outlines future directions, with the aim of providing new insights for the prevention and treatment of immune-related diseases.
Hou X, Li Y, Mu W, Wang H, Ji S
Phage-directed precision microbiome medicine: engineering pathobiont depletion, synbiotic succession, microbial-function editing, metabolite host signaling, neurophagomics, and durable ecological state control in gut dysbiosis associated diseases.Review Frontiers in microbiology | 2026-10-22
Bacteriophages are being investigated as strain-selective tools for modifying intestinal microbial communities, but the evidence supporting ecological reconstruction is substantially less mature than the evidence supporting targeted bacterial depletion. This review separates current knowledge into three domains: established and emerging experimental evidence, human translational evidence, and hypotheses proposed for future testing. Human studies show that orally administered natural or engineered phages can be recovered from the gastrointestinal tract and can alter selected bacterial populations without antibiotic-like loss of overall community diversity. Preclinical studies further demonstrate targeted suppression of inflammatory Klebsiella pneumoniae in inflammatory bowel disease models, cytolytic Enterococcus faecalis in alcohol-associated liver disease, evolutionary steering of Escherichia coli, in situ bacterial genome editing, local therapeutic-protein production, and phage-probiotic cooperation. These findings do not yet establish that an integrated phage-successor-prebiotic sequence can durably reprogram a human gut ecosystem. To organize this translational gap, we use Subtract-Seed-Feed-Lock as an explicitly proposed design framework. A phage or phage-derived platform first depletes, weakens, or edits a disease-relevant bacterial strain or function; a niche-matched successor is then introduced; a selectively utilized nutrient supports that successor; and durability is assessed after treatment withdrawal. Related terms used in this review-Functional Phageability, Minimum Ecological Dose, Ecological Vacancy Window, nutrient-conditioned phagogram, ecological pharmacokinetics/pharmacodynamics (Eco-PK/PD), ecological pharmacovigilance, neurophagomic reverse translation, and microbiome-state digital twin-are hypothesis-generating operational concepts rather than validated clinical methods. Host signaling is likewise framed as predominantly indirect: phage-induced changes in bacterial abundance or function may alter lipopolysaccharide, short-chain fatty acids, indoles, bile acids, and other metabolites that subsequently engage inflammatory, barrier, hepatic, or neural pathways. The gut-brain application remains especially preliminary; targeting urdA-positive imidazole-propionate producers has not been validated with therapeutic phages. Clinical development will require reproducible good manufacturing practice, control of endotoxin and host-cell contaminants, product stability, resistance and immune-neutralization monitoring, environmental-shedding assessment, and regulatory strategies for genetically modified, dynamically updated, and multi-component products. The immediate opportunity is therefore precise microbial perturbation with evidence-matched endpoints; durable programmed reconstruction remains an experimentally testable objective.
Saeed U, Piracha ZZ
Pediatric IBD (13 papers)
Real-world paediatric inflammatory bowel disease surgery: International variation in care and practice. Journal of pediatric gastroenterology and nutrition | 2026-11-10
Paediatric inflammatory bowel disease (IBD) surgery is delivered across heterogeneous settings, with limited paediatric-specific evidence guiding organisation of care, perioperative management, and operative strategy. We characterised contemporary international practice. An international cross-sectional centre-level survey was conducted within the Paediatric IBD Surgery Network. A 28-item questionnaire addressing organisation of care, perioperative management, procedural volumes, and surgical practice was distributed electronically. Analyses were descriptive and performed per question. Twenty-six of 36 invited centres from 14 countries responded (72%). University or teaching hospitals represented 96% of centres, and paediatric surgeons accounted for 69% of respondents. Regular multidisciplinary team meetings were reported by 85%. Use of an enhanced recovery after surgery protocol, structured nutritional screening, and deferral of elective surgery for nutritional optimisation whenever feasible were reported by 50%, 54%, and 42% of centres, respectively. Medication withholding varied, from corticosteroids in 69% of centres to anti-tumour necrosis factor (anti-TNF) agents in 31% and individual newer biologic or small-molecule classes in 15-19%. Formal national centralisation was reported as recommended or mandatory by 42%. Median annual luminal Crohn’s disease surgery volume per centre was two procedures (interquartile range [IQR] 1-5) in 2018, 2.5 (IQR 2-5) in 2022, and 2.5 (IQR 1-5) in 2024. Median annual ileal pouch-anal anastomosis volume in children with ulcerative colitis was 1 (IQR 0.1-3.5). Considerable variation was observed in perioperative optimisation and medication management, integration of medical and surgical therapy, centralisation, and operative strategy. These findings provide a baseline for international benchmarking, consensus development, and prospective collaborative research.
Dotlacil V, Almond S, Destro F, Dreznik Y, Georgopoulos I, Iesalnieks I, Jester I, Kjaer S, Lerner EP, Luglio G
Low-risk paediatric Crohn’s disease: A narrative review of current evidence and unmet research needs.Review Journal of pediatric gastroenterology and nutrition | 2026-11-10
While current paediatric management increasingly favours early intensive treatment for children and adolescents with Crohn’s disease (CD) at high risk of disease progression, a smaller subset of patients presents with a potentially ‘low-risk’ disease phenotype. Identifying these children is clinically challenging, as overtreatment may expose them to unnecessary risks and costs, whereas undertreatment may allow irreversible bowel damage and complications to develop. This narrative review summarises the current evidence on the definition, assessment, treatment, and monitoring of low-risk paediatric CD, highlighting existing knowledge gaps and future research priorities. At present, no consensus definition of low-risk paediatric CD exists, and disease classification relies largely on the absence of recognised high-risk features rather than validated criteria. Similarly, unlike adult practice, no paediatric prognostic model is available to identify children likely to follow a persistently mild disease course. Current assessment requires integration of clinical indices, inflammatory biomarkers, endoscopy, cross-sectional imaging, and evaluation of growth and nutritional status. Dietary treatment (Exclusive Enteral Nutrition and emerging dietary strategies, including the CD Exclusion Diet [CDED] and the Tasty & Healthy [T&H]] remains the commonest induction therapy. Budesonide or antibiotics (azithromycin and metronidazole) represent an appropriate alternative for selected children. CDED and the T&H diet may also represent attractive medium term treatment options, although robust maintenance data are still awaited. Prospective studies are needed to establish a consensus definition, develop paediatric-specific prediction models, optimise risk stratification, and determine the most effective long-term therapeutic and monitoring approaches for the ‘low-risk’ population.
Pochesci S, Scarallo L, Gianolio L, Russell RK
Rising demand for intensive care in pediatric pancreatitis without an increase of case numbers or disease severity: a 16-year retrospective single-center cohort study.Review Molecular and cellular pediatrics | 2026-11-10
Between May 2024 and November 2025 eight children with pancreatitis were treated at our pediatric intensive care unit, seven of them because of the pancreatitis itself. We reviewed all pediatric pancreatitis admissions to our center from 2010 to 2025 in order to clarify whether a trend of case numbers, etiology or severity explains this clustering. All inpatients under 18 years with an ICD-10 code K85-K87 were identified by a search of our central clinical controlling and reviewed based on the INSPPIRE definitions. An episode required lipase or amylase at least three times the contemporaneous upper limit of normal or diagnostic imaging, together with a compatible presentation. Exclusion criteria included, among others, conditions involving exocrine pancreatic insufficiency, such as cystic fibrosis, or patients on follow-up visits. Severity was graded according to the NASPGHAN classification. Of 184 identified admissions, 59 patients met the inclusion criteria: 44 acute, 7 acute recurrent and 8 chronic pancreatitis. Median age was 12 years (IQR 8-16), median stay 7 days (IQR 3-12). Biliary disease and inflammatory bowel disease were the most frequent etiologies with 10 patients each, followed by trauma and genetic variants with 7 each; 4 remained unexplained. The index episode was mild in 26 patients, moderately severe in 25, severe in 5 and could not be graded in 3. 15 patients were treated at an intensive care unit, in 9 of them the pancreatitis was the leading reason. 7 of these 9 admissions occurred in 2024-2025, one each in 2011 and 2014 and none in the nine years in between. The annual number of treated patients did not increase (10 in 2024-2025 versus 49 before), and the proportion of severe disease did not either (1/10 versus 4/49). Case numbers and severity distribution remained stable over 16 years while the need for intensive care rose markedly in the last two years. Referral of complicated cases after advanced pediatric endoscopy became available locally in 2020 and a lower admission threshold are more plausible explanations than a change of the disease. A perceived local increase of severe pediatric pancreatitis should be checked against the complete case series of the center before it is reported as an epidemiological observation.
Kunkel F, Wegner M, Winkler A, Aghdassi A, Bahlmann H, Heckmann M, Baier J
Multiparametric Transperineal Ultrasound Features of Perianal Fistulas in Pediatric Crohn’s Disease: From Baseline to Radiologic Healing. Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine | 2026-11-08
To evaluate and compare the multiparametric transperineal ultrasound (TPUS) features of perianal fistulas at baseline and upon achieving magnetic resonance imaging (MRI)-confirmed radiologic healing in pediatric Crohn disease. This retrospective study included 24 children (22 boys and 2 girls; mean age, 13.0 ± 2.3 years [range, 9-19]) with 45 perianal fistulas evaluated between January 2019 and July 2025. All patients with fistulas who underwent at least 2 TPUS and pelvic MRI assessments and achieved complete healing on MRI were enrolled. Baseline and follow-up TPUS images were evaluated in consensus by 2 radiologists for multiple parameters, including diameter, echogenicity relative to the internal anal sphincter (IAS), vascularity, internal pattern (layered versus homogeneous), anisotropy, presence of pus, air bubbles, abscesses, and adjacent inflammation. Changes in these findings were compared using paired t-tests and McNemar tests. At baseline (n = 45), most fistulas demonstrated higher echogenicity than that of the IAS (73%), exhibited a layered pattern (80%) and internal vascularity (94%) and frequently showed pus (40%) and adjacent inflammation (78%). Despite achieving complete MRI-defined radiologic healing, perianal fistulas remained detectable by TPUS in the majority of cases (60%, 27/45), while the other 18 fistulas (40%) were no longer detectable. However, the 27 persisting fistulas demonstrated significant multiparametric evolution, including reductions in diameter (p < .001), loss of the layered pattern (p < .001), increased anisotropy (p < .001), decreased vascularity (p = .002), and resolution of pus (p = .001) and adjacent inflammation (p < .001). Radiologic healing in pediatric perianal Crohn disease is characterized by distinct multiparametric TPUS changes, including diameter reduction, loss of layered pattern, emergence of anisotropy, and resolution of inflammatory markers. While TPUS serves as a valuable adjunct to MRI for assessing treatment response, the persistent sonographic detectability of fistulas despite MRI-defined healing warrants further validation in larger cohorts and long-term follow-up studies.
Kim S, Ryu YJ, Kim JY, Hahn JW, Yang HR
Crohn’s Disease Requiring Different Surgical Interventions in Presumed Monozygotic Twin Brothers: A Case Report.Case report Surgical case reports | 2026-11-05
Crohn’s disease (CD) in both members of a presumed monozygotic twin pair is uncommon. We report twin brothers who developed ileocolonic and perianal CD 2 years apart but required different surgical interventions. This report highlights the value of prompt evaluation of a symptomatic cotwin and individualized surgical decision-making. Twin 1 developed a perianal abscess at the age of 16 years, followed by severe rectosigmoid inflammation and fixed stenosis. Endoscopy demonstrated rectosigmoid mucosal necrosis, ileocecal scarring, and longitudinal ulcer scars in the small bowel, and biopsy specimens contained epithelioid granulomas. Recurrent obstructive symptoms led to an anterior resection. Twin 2 developed a perianal abscess at the age of 18 years. Because his cotwin had CD, he underwent early ileocolonoscopy, which showed longitudinal ulcers extending from the terminal ileum to the cecum and aphthous ulcers throughout the colorectum. A symptomatic low intersphincteric fistula was treated by seton drainage, and curetted tissue contained epithelioid granulomas. Both brothers initially received vedolizumab after surgery. All seton-related drains in Twin 2 were removed 3 months postoperatively. Drainage from the fistula recurred at 6 months, prompting a switch from vedolizumab to adalimumab; the drainage ceased 1 month later. Zygosity was reported by the patients and their family but was not genetically confirmed. Twin 1 remained free of recurrent obstruction for more than 2 years. This rare presumed monozygotic twin pair showed close concordance in the age at onset, ileocolonic and perianal involvement, and granulomatous histology, while requiring different operations and postoperative medical strategies. Their clinical courses underscore the importance of asking about family history, promptly investigating gastrointestinal or perianal symptoms in a cotwin, and individualizing treatment over time. Further accumulation of well-characterized twin cases with objective zygosity assessment and long-term follow-up may clarify the shared and divergent clinical features of CD.
Matsunaga K, Matsuda K, Kotani T, Abe K, Kondo R, Omichi K, Nishikawa T, Masuda W
Normative Measures of Colon Length in Children With Inflammatory Bowel Disease, Aged 11-17 Years, Based on MRI. Clinical anatomy (New York, N.Y.) | 2026-11-05
To better understand (abnormal) colonic anatomy on imaging, data on normal colonic anatomy in the unaffected population are crucial. We assessed colon lengths in children without constipation on MRI. This retrospective study included patients (< 18 years), who underwent MRI-enterography between 2016 and 2020 for suspected inflammatory bowel disease, and did not meet Rome-IV criteria for functional constipation. Patients with colonic inflammation were excluded. Primary outcome was the mean total colon length/BSA (cm/m2) (95% CI; ±2SD), and the secondary outcomes were total colon length (cm), rectosigmoid length/BSA (cm/m2), and rectosigmoid length (cm). Colon segments were independently measured on coronal T2-weighted MRI using 3D multiple-point measurements. Linear regression was used to evaluate associations between total colon length and sex, age, height, weight, body surface area (BSA). Eighty-one patients (median age 15 years; range 11-17; 53% male) were included. The mean total colon length/BSA was 72.9 ± 21.0 cm/m2. Mean total colon length was 115.8 ± 13.8 cm, mean rectosigmoid length/BSA was 24.2 ± 12.3 cm/m2, and mean rectosigmoid length was 38.2 ± 7.9 cm. Additionally, we assessed colonic segments per age group. Colon length significantly correlated with age (p = 0.03), height (p < 0.001), weight (p < 0.001), and BSA (p < 0.001). In a multivariable linear regression analysis, BSA was significantly correlated with total colon length (95% CI 21.4-49.4; p < 0.0001). This study provides data on colon and rectosigmoid lengths in children, aged 11-17 years, without constipation measured on MRI-enterography. This knowledge can be used for the identification of abnormal colonic anatomy in children with therapy-resistant constipation on imaging.
Jonker CAL, Gorter RR, Benninga MA, Koppen IJN, de Jonge CS, de Jong JR, van Schuppen J
Beyond the gut: Non-specific interstitial pneumonia in pediatric ulcerative colitis-A rare extra-intestinal manifestation. JPGN reports | 2026-11-05
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder often presenting with extra-intestinal manifestations (EIMs) involving the skin, joints and eyes. However, pulmonary manifestation, such as interstitial lung disease (ILD), is a rare complication, particularly in the pediatric population. We report a case of a 10-year-old boy, with very early onset IBD-ulcerative colitis, presented with non-productive cough, fever and dyspnea, with examination findings revealing respiratory distress, pallor, clubbing and pyoderma gangrenosum. High-resolution computed tomography (HRCT) was suggestive of bilateral diffuse ground-glass opacities with intralobular septal thickening and tractional bronchiectasis, consistent with non-specific interstitial pneumonia (NSIP). Furthermore, the patient developed septic shock and macrophage activation syndrome, requiring intensive care management and immunosuppression. This case highlights that even in the setting of silent intestinal disease activity of a pediatric IBD case, the patient can have potentially life-threatening pulmonary EIMs, warranting early diagnosis and treatment.
Vachher H, Poojari V, Tetarbe S, Chandane P, Shobhavat L, Shah I
Clinical features and outcomes of perianal disease in pediatric-onset Crohn’s disease: A comparative analysis according to age at diagnosis. BMC gastroenterology | 2026-11-03
This study aimed to investigate the clinical features, treatment responses, and outcomes of pediatric patients with Crohn’s disease (CD) and perianal disease (PD) in China, with a particular focus on age at diagnosis. We retrospectively analyzed 144 children diagnosed with CD between 2015 and 2024. Patients were divided into PD and non-PD groups and further stratified by age at diagnosis into very-early onset (VEO-IBD, < 6 years) and late-onset disease (LO; 6-18 years). The clinical, endoscopic, and genetic data were compared between the groups. The overall prevalence of PD was 57/144 (39.58%). VEO-IBD cases accounted for 44/144 (30.56%) of cases, of whom 22/44 (50.00%) had concurrent PD; among these VEO-PD patients, the monogenic mutation rate was 17/22 (77.27%), predominantly involving IL-10RA. In the full cohort, PD was associated with increased colonic involvement (25/57 [43.86%] vs. 17/87 [19.54%], P < 0.05), greater disease severity (severe PCDAI: 25/57 [43.86%] vs. 20/87 [22.99%], P < 0.05), and lower clinical remission rates (41/57 [71.93%] vs. 83/87 [95.40%], P < 0.05). In the LO subgroup, patients with PD were treated with biologic agents significantly earlier, with clinical remission of perianal lesions reaching 30/35 (85.71%). VEO-IBD with PD was associated with monogenic mutations, greater disease activity, and lower clinical remission. VEO-PD had poorer outcomes than VEO-IBD without PD, although mortality was similar. In selected monogenic VEO-IBD patients, thalidomide and/or HSCT may be individualized options, but thalidomide should not be generalized to all VEO-IBD.
Mi M, Jin M, Meng L, Gong Y, Zhong X
Impact of emotion regulation on psychosocial and emotional problems in Dutch adolescents with inflammatory bowel disease. JPGN reports | 2026-11-03
Adolescents with inflammatory bowel disease (IBD) are at increased risk of psychosocial and emotional problems. This study examined the role of emotion regulation (ER) to (1) determine the prevalence of psychosocial and emotional problems in adolescents with IBD, (2) examine associations with sociodemographic and clinical characteristics, and (3) evaluate associations with ER strategies. Adolescents (ages 12-17 years) with IBD from three Dutch medical centers completed routine psychosocial screening. Psychosocial and emotional problems were assessed with the Strengths and Difficulties Questionnaire (SDQ). Norm comparisons were performed using one-sample t-test on raw SDQ scores, and prevalence estimates were based on age- and sex-specific percentile scores. ER strategies (adaptive, maladaptive) were measured with the Dutch FEEL-KJ. Sociodemographic and clinical data were obtained from medical records/questionnaires. Associations were examined using Spearman correlations and stepwise multiple regression, with psychosocial and emotional problems as outcomes. Compared with Dutch population-based norms, adolescents with IBD reported significantly higher psychosocial and emotional problems than reference norm groups (p < 0.001). Elevated scores were observed in 64.3% for total difficulties and 42.9% for emotional problems. Maladaptive ER showed strong positive associations with both outcomes. Sociodemographic and clinical characteristics were not significantly associated with psychosocial or emotional problems. Maladaptive ER is a prominent correlate of psychosocial and emotional problems in adolescents with IBD, whereas background characteristics were not supported. Targeting dysfunctional ER strategies may facilitate early identification of at-risk adolescents and guide timely interventions.
Jansen-Kamphorst S, Snetselaar R, Greidanus J, Hartman EE, van Pelt M, Stapelbroek J, Vugs B
ECCO Topical Review: Inflammatory Bowel Disease-Like Patterns of Drug Colitis with Practical Guidance and a Focus on Immune Checkpoint Inhibitor-Induced Enterocolitis.Review★ Journal of Crohn’s & colitis | 2026-11
Drug-induced enterocolitis (DIC) consists of a heterogeneous group of gastrointestinal inflammatory disorders with clinical, endoscopic, and histological features that often overlap with inflammatory bowel disease (IBD). Given the increasing recognition of immune checkpoint inhibitor (ICI)-induced enterocolitis and the lack of standardized management algorithms, the European Crohn’s and Colitis Organisation (ECCO) convened a multidisciplinary panel to review DIC, with a particular focus on ICI-induced disease. Gastroenterologists, histopathologists, and oncologists systematically reviewed the literature using Medline, PubMed, EMBASE, and Scopus. Evidence was synthesized into ECCO Current Practice Positions addressing diagnostic principles, histopathological patterns, therapeutic strategies, and ICI-specific considerations. Statements were refined and approved through structured consensus. Twenty-three practice positions were agreed upon. DIC may present with diverse histological patterns, including IBD-like/chronic enterocolitis, acute enterocolitis, microscopic colitis, ischemic-type injury, and mixed features, none of which are pathognomonic. Close clinicopathological collaboration is therefore essential. In suspected ICI-induced enterocolitis, assessment should include Common Terminology Criteria for Adverse Events-based grading, stool testing for pathogens, fecal calprotectin, endoscopy with biopsies, and imaging when indicated. Corticosteroids remain first-line therapy, while mild or microscopic disease may respond to budesonide or beclomethasone. Corticosteroid-refractory or corticosteroid-dependent disease should prompt early escalation to infliximab or vedolizumab. Surgery is reserved for refractory or complicated cases. Rechallenge with ICIs may be considered following multidisciplinary evaluation. DIC represents a diagnostically complex spectrum of disorders that require integrated multidisciplinary evaluation. These ECCO Current Practice Positions provide a practical framework for diagnostic work-up and treatment, particularly for ICI-induced enterocolitis.
Verstockt B, Dragoni G, van Schaik F, Nunes PB, Burisch J, Carbonnel F, Dekervel J, Driessen A, Ordás I, Powell N
B cell/adipocyte crosstalk amplifies MCP-1 secretion, M2-like macrophage accumulation, and polarization in gut-associated, inflamed adipose tissue.★ Journal of Crohn’s & colitis | 2026-11
During Crohn’s disease (CD), hyperplasia of the mesenteric white adipose tissue (WAT), called creeping fat (CrF), is associated with the accumulation of immune cells. Here we investigated the impact of B cell/adipocyte crosstalk on immune cell recruitment and inflammation within inflammatory bowel disease-related adipose tissue. We used flow cytometry and in vitro 3D culture systems of biopsies from CrF of CD patients as well as a mouse model of intestinal inflammation, in vitro co-cultures, mass spectrometry, and single-cell RNA sequencing to evaluate the impact of B cell/adipocyte interplay on monocyte chemoattractant protein-1 (MCP-1) production and macrophage polarization. Employing primary human and mouse 3D adipocyte cultures, we observed that adipocytes from CD patients displayed a persistent inflammatory phenotype even after prolonged time in culture, a cytokine secretion profile also recapitulated via lipopolysaccharide stimulation. Analyzing CrF of CD patients as well as WAT of a mouse model of intestinal inflammation, we found an accumulation of B cells. B cell/adipocyte co-cultures led to elevated secretion of MCP-1 by primary adipocytes, facilitating macrophage migration. Consequently, co-transfer of B cells with T cells increased T cell activation and M2-like macrophage accumulation in inflamed mouse WAT. Mass spectrometry and single-cell RNA sequencing analyses suggested that the B cell/adipocyte crosstalk establishes a microenvironment that may promote M2-like macrophage polarization. B cell/adipocyte interactions in CD-associated inflamed adipose tissue increase MCP-1 and lactate, promoting recruitment and M2-like polarization of macrophages, likely amplifying local WAT inflammation.
Goess MC, Heinze JM, Hofmann J, Buck A, Gadjalova I, Weber MC, Ring S, Buescher JM, Villa M, Neumann PA
Serum vitamins and inflammatory bowel disease in children: a case-control study.Observational study Frontiers in immunology | 2026-10-26
Micronutrient deficiencies are common in pediatric inflammatory bowel disease (IBD), yet data on multiple vitamin profiles remain limited. This study aimed to comprehensively evaluate serum vitamin levels in children with IBD and explore their associations with immune cell profiles. A retrospective observational study was conducted at the Children’s Hospital Affiliated to Zhengzhou University. A total of 46 children diagnosed with IBD who had vitamin profiling were enrolled between March 2022 and March 2026. A control group of 46 healthy children, who underwent health check-ups and vitamin assessments during the same period, were also included, matched 1:1 for age and sex. Clinical and laboratory data were retrieved from the hospital’s electronic medical record system. Serum levels of vitamins A, D, E, K, B1, B2, B3, B5, 5-methyltetrahydrofolate, and C were measured using ultra-high performance liquid chromatography-tandem mass spectrometry. Compared with controls, IBD patients had significantly lower vitamin A (VA) and vitamin C (VC) levels, while vitamin E (VE) levels were higher (all P < 0.05). Deficiency rates of VA (76.1% vs. 28.3%), VC (50.0% vs. 26.1%), and vitamin D (41.3% vs. 21.7%) were significantly increased in the IBD group (all P < 0.05). Within the IBD cohort, VA, VD, and VC levels correlated significantly with neutrophil and lymphocyte percentages. Multivariate logistic regression identified lower VA level (OR = 0.159, 95% CI: 0.032-0.792, P = 0.025) and VA deficiency (OR = 7.800, 95% CI: 1.735-35.055, P = 0.007) as factors independently associated with IBD. Pediatric IBD patients exhibit significant deficiencies in VA, VC, and VD, and within the IBD cohort, these vitamins (VA, VD, and VC) correlate significantly with neutrophil and lymphocyte percentages. Multivariate regression suggests a potential independent association between VA status and pediatric IBD, though these are preliminary observational findings. This study provides preliminary multi-vitamin profiling data for pediatric IBD, highlighting the need for attention to VA and VC deficiencies alongside routine VD monitoring. Further validation in larger multicenter cohorts is required.
Li X, Li T, Wang Y, Li Y, Zhang S, Yan W, Ma Y, Li Z, Yang J, Jin Z
Context-dependent functions of insulin, IGF, and GLP signaling in inflammatory bowel disease: linking metabolism, immunity, and intestinal homeostasis.Review Frontiers in immunology | 2026-10-21
Inflammatory bowel disease (IBD), encompassing Crohn’s disease and ulcerative colitis, is a chronic relapsing inflammatory disorder of the gastrointestinal tract characterized by dysregulated immune responses, impaired epithelial barrier function, and alterations in the gut microbiota. Although considerable progress has been made in understanding the immunopathogenesis of IBD, increasing evidence indicates that metabolic signaling pathways are integral regulators of intestinal inflammation, tissue repair, and disease progression. Among these, insulin, insulin-like growth factors (IGFs), and glucagon-like peptides (GLPs) constitute an interconnected immunometabolic network that links nutrient sensing, energy metabolism, epithelial regeneration, and immune homeostasis. Insulin signaling plays context-dependent roles in IBD by regulating glucose metabolism, epithelial repair, inflammatory responses, and interactions with the gut microbiota and bile acid metabolism. While insulin promotes mucosal healing and barrier restoration in intestinal epithelial cells, excessive activation of insulin signaling in immune cells may exacerbate chronic inflammation through epigenetic and cytokine-mediated mechanisms. The IGF axis is also profoundly altered during active IBD, with systemic suppression of IGF-1 and IGFBP-3 accompanying disease activity, whereas local IGF signaling promotes epithelial regeneration, wound healing, and immune regulation. In addition, IGF-binding proteins (IGFBPs) function as active modulators of inflammation, fibrosis, and colitis-associated colorectal cancer in an isoform-specific manner. GLP signaling further integrates metabolism with intestinal immunity; GLP-1 receptor agonists exhibit anti-inflammatory, metabolic, and microbiota-modulating effects, whereas GLP-2 primarily enhances epithelial proliferation, barrier integrity, and mucosal repair. Emerging preclinical and observational clinical studies suggest that GLP-based therapies may improve disease outcomes, although prospective randomized trials are still required. This review summarizes current knowledge regarding the biological functions and molecular mechanisms of insulin, IGFs, IGFBPs, and GLPs in IBD, highlighting their coordinated roles in regulating metabolism, immunity, epithelial homeostasis, and tissue remodeling. A better understanding of these interconnected signaling pathways may facilitate the development of novel immunometabolic therapeutic strategies aimed at promoting mucosal healing, limiting chronic inflammation, and improving long-term outcomes in patients with IBD.
Abuhussein E, Yamaguchi Y, Singh DK, Orahovats CE, Nishiyama K, Tsuboi K, Huang L
Pathogenesis & Basic Science (12 papers)
Weiling decoction alleviates dampness-exacerbated ulcerative colitis in a spleen-deficient mouse model: associations with the gut microbiota composition and TLR4/NF-κB-related inflammatory responses. 3 Biotech | 2026-11-09
In this study, we evaluated the effects of the Weiling decoction on humid environment-induced spleen deficiency with dampness pattern ulcerative colitis (UC) in mice and its correlations with the gut microbiota, circulating lipopolysaccharide (LPS)/cytokines, and Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) inflammatory markers. A mouse model was established using 2% DSS and Folium sennae by gavage, and the mice were exposed to a humid environment for 21 days, after which the Weiling decoction was administered during the final 7 days. Colonic injury was assessed by the disease activity index (DAI) and hematoxylin and eosin (H&E) staining. Serum LPS and cytokine levels were measured by ELISA. The TLR4/NF-κB pathway and mucosal immune microenvironment indicators were evaluated by Western blotting, RT-qPCR, and immunofluorescence. 16S rRNA sequencing was employed to determine the composition of the colonic microbiota. Weiling decoction treatment significantly reduced DAI scores, attenuated colonic shortening, and ameliorated histopathological damage. Serum proinflammatory cytokines and LPS decreased, while interleukin-10 (IL-10) expression increased. Treatment with Weiling decoction downregulated TLR4/NF‑κB expression and CD86-positive signals, whereas CD163-positive signals were upregulated. 16S rRNA sequencing revealed that Weiling decoction modulated the composition of the gut microbiota. Correlation analysis revealed that UCG-005, NK4A214_group, and Odoribacter were negatively correlated with inflammatory indices, whereas Faecalitalea was positively correlated. These findings suggest that Weiling decoction alleviates dampness-exacerbated UC in mice with a spleen deficiency with dampness pattern through mechanisms associated with gut microbiota modulation, reduced circulating LPS levels, and suppressed TLR4/NF-κB-mediated inflammation. These findings provide mechanistic insights and empirical support for the traditional “dampness-eliminating and spleen-strengthening” approach to colitis therapy. The online version contains supplementary material available at https://doi.org/10.1007/s13205-026-05080-8.
Tian Q, Yu D, Zhang X, Tan Z, Xiao N, Cai Y
α-tocopherol (Vitamin E) inhibits second mitochondria-derived activator of caspases (SMAC) mimetic-induced cell death by directly targeting cIAP1 degradation.★ British journal of pharmacology | 2026-11-08
Tocopherols (vitamin E) are well characterized as essential lipophilic antioxidant agents. However, recent evidence suggests that tocopherols may also regulate cellular signalling through direct interactions with specific protein targets. This study aimed to investigate the molecular mechanism by which α-tocopherol regulates programmed cell death and to identify its direct molecular target. A high-throughput screen identified α-tocopherol as an inhibitor of TNF-α/SMAC-mimetic-induced cell death. The mechanism(s) underlying this action of α-tocopherol was investigated using western blotting, immunoprecipitation, ubiquitination assays, drug affinity responsive target stability, cellular thermal shift assay, isothermal titration calorimetry and molecular docking. Its efficacy, in vivo, was evaluated in a murine model of ulcerative colitis, induced by dextran sulphate sodium (DSS). α-Tocopherol selectively inhibited TNF-α/SMAC-mimetic-induced cell death by directly and competitively binding to the BIR3 domain of the inhibitor of apoptosis protein-1 (cIAP1). This interaction stabilized cIAP1, prevented the formation of RIPK1-dependent death complexes and suppressed apoptosis and necroptosis. In a murine model of DSS-induced colitis, α-tocopherol significantly alleviated disease severity while preserving cIAP1 protein expression. Our findings identified cIAP1 as a previously unrecognized molecular target of α-tocopherol and demonstrated that cIAP1 stabilization contributed to the suppression of RIPK1-dependent cell death. These findings expand the current understanding of the biological functions of tocopherols and provide a mechanistic basis for their potential therapeutic application in inflammatory diseases associated with aberrant cIAP1 degradation.
Zhu J, Tian X, Zhao Y, Yang F, Wang R, Wang F, Wang Z, Zhang T, Ren W, Tang C
Integrated bioinformatic and molecular analyses reveal the IRF1-TGM2 axis in regulating oxidative stress and apoptosis in in vitro CD-like intestinal epithelial cell models. Molecular genetics and genomics : MGG | 2026-11-07
Crohn’s disease (CD) is a chronic recurrent inflammatory bowel disease (IBD). Transglutaminase 2 (TGM2) participates in CD progression, yet its regulatory mechanism remains elusive. Here, transcriptomic, single-cell transcriptomic, metabolomic, and apoptosis-related datasets from GEO, Metabolomics Workbench, and GeneCards were integrated, followed by bioinformatic analyses using R 4.5.1 and MetaboAnalyst 5.0. In vitro experiments included Western blot, cell transfection, TUNEL, ELISA, ROS detection, ChIP, dual-luciferase reporter assay, and RT-qPCR. Bioinformatic analyses identified distinct gene expression profiles, aberrant immune cell infiltration, and disrupted energy and lipid metabolism in CD, yielding 23 candidate targets. TGM2 was enriched in fibroblasts, enterocytes, and myeloid cells, modulating apoptosis, inflammation, and oxidative stress to aggravate CD phenotypes. Mechanistically, interferon regulatory factor 1 (IRF1) directly bound to the TGM2 promoter and enhanced its transcription. The IRF1-TGM2 axis regulated apoptosis, inflammation, and ROS levels, with TGM2 overexpression reversing the inhibitory effects of IRF1 knockdown. IRF1 transcriptionally upregulates TGM2 to promote apoptosis and oxidative stress, providing a plausible mechanistic framework for CD-associated epithelial injury.
Wang C, Zhang C, Wu C, Lin G, Shao Y, He M
Rat strain differences In TNBS-induced colitis: the antibody and cytokine profile behind the superior survival of albino oxford rats. Immunologic research | 2026-11-05
Inflammatory bowel disease is a chronic intestinal inflammation resulting from host-microbial interactions in genetically susceptible individuals. Two rat strains, Albino Oxford and Dark Agouti, differ in gut microbiota composition and the overall intensity of inflammatory responses. We investigated whether trinitrobenzenesulfonic acid-induced colitis in these two rat strains may be useful for studying therapies for colitis. Male Albino Oxford and Dark Agouti rats were treated intrarectally with trinitrobenzenesulfonic acid and monitored for 7 days. Colon tissue, peritoneal cavity and mesenteric lymph node cells were analysed for nitric oxide, urea and cytokine production, and peritoneal and lymph node cell phenotypes were determined by flow cytometry. Dark Agouti rats exhibited higher mortality following colitis induction than Albino Oxford rats, with longer segments of colonic necrosis/inflammation and a higher relative IL-17 A/IFN-γ balance in colon tissue and lymph node cells. Dark Agouti rats showed an increased proportion of neutrophils and a reduced proportion of macrophages in the peritoneal cavity, as well as a robust IL-6 response by peritoneal cavity cells. In contrast, Albino Oxford rats displayed a higher proportion of resident peritoneal cavity macrophages and lymphocytes in lymph nodes, and markedly increased production of IL-10 and urea by peritoneal cavity cells. The genetically determined inflammatory phenotype of Dark Agouti rats, in contrast to the less inflammatory character of Albino Oxford rats, may serve as a useful model for investigating therapies that target inflammatory processes in colitis. The use of rats with distinct inflammatory characteristics may help identify specific molecular targets in non-responsive individuals.
Stanojević S, Ćuruvija I, Prijić I, Vujić V, Vasić M, Bogdanović A, Blagojević V
Screening of anti-ulcerative colitis components from Guizhou ethnomedicines and mechanism study of lupenone in DSS-induced ulcerative colitis mice: In silico prediction and in vivo validation. International immunopharmacology | 2026-11-05
Ulcerative colitis (UC) is a refractory chronic intestinal inflammatory disorder with limited and relapse-prone conventional therapies. Guizhou heat-clearing and detoxifying medicinal plants exhibit potent anti-inflammatory activity and promising potential for UC treatment, yet their core bioactive constituents and underlying mechanisms remain unclear, hindering further development. This study aimed to screen anti-UC bioactive components from 133 ethnomedicines and explore their mechanisms via integrated network pharmacology, molecular docking and molecular dynamics (MD) simulation. An acute DSS-induced mouse model of UC was established for in vivo validation. Western blot (WB), RT-qPCR and quantification of intestinal short-chain fatty acids (SCFAs) were then performed to assess UC-related indicators. 12 core components including lupenone and caudatin were identified. MD simulations confirmed stable binding between lupenone and NF-κB p65. Lupenone alleviated UC symptoms and downregulated the mRNA and protein levels of colonic TLR4, NF-κB p65, NLRP3 and Caspase-1, and reduced TNF-α, IL-1β, IL-6, and IL-17. It restored SCFAs homeostasis by increasing acetic and butyric acid while decreasing hexanoic acid. Correlation analysis revealed that inflammatory targets and IL-1β were negatively correlated with acetic and butyric acid but positively correlated with hexanoic acid. Collectively, lupenone serves as the core bioactive constituent of Guizhou heat-clearing and detoxifying medicinal plants against colitis. This study confirms that lupenone effectively ameliorates acute DSS-induced ulcerative colitis in mice. It suppresses the TLR4/NF-κB/NLRP3 inflammatory cascade, reduces pro-inflammatory cytokine release, and modulates acetic, butyric and hexanoic acid levels to restore intestinal short-chain fatty acid homeostasis. This research strategy offers a reference for high-throughput screening of natural bioactive products.
Yang Z, Zeng Q, Liu Y, Ding Q, Qin P, Liu M, Wu H, Xu F, Wang X
STAG Priming Preserves Paneth Cells and Limits Parasite-Triggered Ileitis. Immunology and cell biology | 2026-11-04
Toxoplasma gondii triggered ileitis is a commonly used model for diseases affecting the small intestine, such as Crohn’s Disease. Inflammation is primarily dependent on Th1-mediated killing of Paneth cells, which consequently promotes intestinal dysbiosis and boosts inflammation and pathology in the organs. Priming of the immune system with soluble Toxoplasma antigen (STAG) has been shown to induce immune regulation in several inflammatory diseases. Herein, we describe how protection of Paneth cells by priming with STAG is associated with protection against T. gondii triggered ileitis. We observed that STAG priming diminished intestinal pathology and modulated cytokine profile, and specifically downregulates interferon expression. Consequently, priming with STAG sustained Paneth-cell numbers during infection, unlike non-immunized controls, and thus also retained antimicrobial protein expression. Interestingly, we show that naturally resistant BALB/c mice did not undergo total Paneth-cell ablation, but upon additional Paneth-cell depletion, presented intestinal pathology and tissue parasitism levels similar to susceptible C57BL/6. Finally, we show that the STAG-primed groups presented a different intestinal microbiota, primarily through promotion of a protective microbiota enriched in Firmicutes and depleted of Enterobacteriaceae. Thus, the results suggest that priming with STAG is able to prevent Paneth-cell depletion and is associated with resistance to T. gondii triggered ileitis.
Araujo ECB, Sousa LA, Briceno MP, Coutinho LB, Martins AAB, Fenton A, Sankaran-Walters S, Czarnewski P, Silva NM
Gramine alleviates ulcerative colitis by targeting COX-2 and inhibiting ferroptosis. Journal of ethnopharmacology | 2026-11-04
Arundo donax Linn is a well-known herbal remedy in traditional healing systems that is commonly indicated for fever, toothache, and dysuria, as documented in the Chinese medicinal literature. Gramine (GRA) is an alkaloid derived from the rhizome of Arundo donax, and studies have confirmed its antiviral, antibacterial, anti-inflammatory, and anticancer properties. However, its specific pharmacological mechanism in the context of ulcerative colitis (UC) has yet to be systematically elucidated. The objective of this study was to elucidate the protective role and mechanisms of GRA in UC. Network pharmacology and bioinformatics analyses were performed to identify potential targets associated with UC, ferroptosis, and GRA. The direct binding of GRA to COX-2 was confirmed using surface plasmon resonance (SPR), molecular docking, and molecular dynamics (MD) simulations. An in vivo model of UC was established in mice via the administration of 3% dextran sulfate sodium (DSS). In this UC model system, we evaluated the effects of GRA and celecoxib (CEL) alone and in combination. Histopathological changes, intestinal epithelial barrier function, and the levels of ferroptosis-related markers were assessed. Additionally, the combined effects of GRA and CEL on ferroptosis and intestinal barrier integrity were further evaluated in a lipopolysaccharide (LPS)-stimulated NCM460 cell model of colitis. The network pharmacology analysis identified COX-2 as a core target connecting ferroptosis, UC, and GRA. Direct binding between GRA and COX-2 was subsequently confirmed using molecular docking, MD simulations, and SPR. In vivo, GRA treatment significantly reduced the disease activity index (DAI), histological damage, and cell death in mice with colitis. Further investigation revealed the induction of ferroptosis in mice with colitis, as evidenced by iron overload, glutathione (GSH) depletion, increased reactive oxygen species (ROS) and malondialdehyde (MDA) levels, and upregulated of COX-2 expression. Treatment with GRA, CEL, or their combination significantly ameliorated these ferroptosis-related alterations. Transmission electron microscopy further revealed that GRA counteracted intestinal barrier disruption. Consistently, in vitro experiments demonstrated that all three treatments: GRA, CEL, and GRA + CEL, effectively inhibited ferroptosis and preserved intestinal barrier integrity, thereby mitigating UC pathology. Notably, the results of both in vitro and in vivo experiments indicated that the combination therapy of GRA and CEL (GRA + CEL) exhibited superior efficacy compared with either GRA or CEL treatment alone. Our study demonstrated that GRA alleviates UC by protecting the intestinal barrier; notably, GRA + CEL treatment exerted greater therapeutic effects than GRA or CEL alone. The potential underlying mechanism may involve the mitigation of ferroptosis by GRA through the inhibition of COX-2.
Zhu Z, Li R, Liao W, Huang X, Xia Y, Zhu N, Yu X, Li Q, Hu M, Liu Y
The role of NLRC5 in human inflammatory bowel diseases and murine experimental colitis.Review Journal of immunology (Baltimore, Md. : 1950) | 2026-11
Nucleotide-binding, leucine-rich repeat-containing (NLR) innate immune proteins have been implicated in inflammatory bowel diseases (IBD). NLRC5 is a key trans-activator of class I MHC (MHC-I) genes, but it is also found to regulate cytokines and cell death. Meta-analysis of 14 different human RNAseq or microarray data (total n = 1,093) revealed a consistent and strong association between IBD and heightened NLRC5 expression, suggesting a role for NLRC5 across diverse IBD patients. Furthermore, these data show a strong correlation of NLRC5 with inflammation and STAT1 signatures, suggesting that its role in human IBD may extend beyond its canonical role as a regulator of MHC-I, or that its expression is controlled by inflammation/STAT1. However, in the dextran sulfate sodium (DSS)-induced colitis mouse model, Nlrc5 protected against colitis, which mimicked B2m-/- mice lacking MHC-I. This Nlrc5-associated protection has been consistent across hundreds of mice over a decade in the hands of several investigators. Microbiome study found significant alterations in the microbiota in overall composition and strain-specific differences over time, suggesting a dynamic relationship between microbiome dysbiosis and Nlrc5. To resolve these issues, we studied germ-free (GF) wild-type and Nlrc5-/- mice. Surprisingly, GF mice showed that Nlrc5 exacerbated instead of protected against DSS-induced colitis. A major difference between GF and conventionally-raised mice is that DSS reduced Nlrc5/ 2m expression in GF mice, while it did the opposite in SPF mice. These data highlight the complex role of Nlrc5 and the microbiome in the pathogenesis of IBD, as well as the necessity of complementary mouse models.
Fay BP, Tam J, Wrobel JA, Huang G, Chou WE, Sheikh SZ, Furey TS, Sartor RB, Guo H, Ting JP
Enteric Neurons and Glial Cells Are Partially Protected in P2X7 Receptor-Deficient Mice With Ulcerative Colitis. Neurogastroenterology and motility | 2026-11
Inflammatory bowel diseases, such as colitis, cause enteric nervous system dysfunction. Purinergic signaling through the P2X7 receptor (P2X7R) is activated during intestinal inflammation by extracellular ATP, but its role in chronic colitis remains unclear. Investigate the effects of an experimental colitis model on the ENS from mice knockout (KO) of P2X7R. Colitis was induced in wild-type (WT) and KO mice by three cycles of Dextran Sodium Sulfate (DSS) (Cycles 1 and 2, 2% and Cycle 3, 1.5%) dissolved in drinking water for 5 days, followed by drinking water for the next 14 days (KO/DSS and WT/DSS groups). The KO/SHAM and WT/SHAM groups received water during the same period. The animals were euthanized after 57 days, and the distal colon was collected. Disease activity index and histological analysis were performed. Whole-mount preparations of the myenteric plexus were analyzed by immunofluorescence for neuronal nitric oxide synthase (nNOS), acetylcholine transferase (ChAT), β3-Tubulin, P2X7R, glial fibrillary acidic protein (GFAP), and S100β, and the inflammasome component NLRP3. Neuronal and glial densities were quantified. Chronic DSS-induced colitis decreased the nitrergic and cholinergic neurons, β3-tubulin-ir neurons, and GFAP-ir and S100β glial cells in WT/DSS and KO/DSS groups. P2X7R-ir cells decreased in WT/DSS animals, and NLRP3-ir cells increased mostly in WT/DSS, indicating inflammasome activation. There were changes in neuronal profile areas. These findings were significantly attenuated in P2X7R KO mice, indicating neuronal protection during chronic inflammation. Experimental colitis affected the ENS of the distal colon. A slight neuronal attenuation of nNOS-expressing neurons was observed in the P2X7RKO.
Souza RF, Caetano MAF, De Paulo CB, Castelucci P
Potential Anti-inflammatory Compounds in Shaoyao Decoction to Treat Ulcerative Colitis Explored by Bioaffinity Ultrafiltration Liquid Chromatography-Mass Spectrometry With Multiple Drug Targets. Journal of separation science | 2026-11
Shaoyao Decoction (SYD) demonstrates therapeutic efficacy in ulcerative colitis (UC), though its active components are still unclear. The present investigation was conducted to comprehensively identify those major constituents of SYD responsible for therapeutic action, focusing on their interaction with important inflammation-related mediators, NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3), interleukin-6 (IL-6), and cyclooxygenase-2 (COX-2). In view of this, ultra‑high‑performance liquid chromatography-quadrupole time‑of‑flight tandem mass spectrometry (UHPLC-Q-TOF-MS/MS) coupled with a multi-target affinity ultrafiltration strategy was established for the screening of bioactive compounds. Analysis performed by UHPLC-Q-TOF-MS/MS indicated the presence of 43 compounds within SYD. Positive-ion-mode analysis resulted in the identification of 24 constituents; most of them are flavonoids, including baicalin, jatrorrhizine, and wogonin 7-O-glucuronide. Under negative ion conditions, 23 compounds were detected; these were mainly organic acids and glycosides, including 4,5-dicaffeoylquinic acid, liquiritin, and gallic acid. The bioaffinity ultrafiltration selection profiles indicated that the compounds jatrorrhizine, gallic acid, glycyrrhizic acid, 4,5-dicaffeoylquinic acid, wogonin 7-O-glucuronide, and galloyl paeoniflorin exhibited excellent binding capability with the three inflammatory target enzymes. Notably, jatrorrhizine exhibited binding activity with all three target enzymes in positive ion mode. Gallic acid achieved a binding affinity of 54.68% for IL-6 in negative ion mode, and compounds glycyrrhizic acid, 4,5-dicaffeoylquinic acid, wogonin 7-O-glucuronide, and galloyl paeoniflorin, among others, all exhibited strong binding affinities for both NLRP3 and COX-2. Molecular docking simulations reinforced these binding findings, further substantiating the potential synergistic mechanisms by which SYD components act upon the inflammatory targets. This study characterizes the chemical profiling of SYD and reveals that jatrorrhizine, gallic acid, glycyrrhizic acid, 4,5-dicaffeoylquinic acid, wogonin 7-O-glucuronide, and galloyl paeoniflorin may serve as the primary bioactive components in SYD for treating UC through inhibition of COX-2, NLRP3, and IL-6, thereby offering theoretical support for its clinical use and future development.
Wang S, Hua X, Liu D, Sarker SD, Nahar L, Zhang Y, Guo M
Ameliorative Effects and Underlying Molecular Mechanisms of Nootkatone in DSS-Induced Ulcerative Colitis in Mice. Journal of inflammation research | 2026-10-30
Nootkatone (NKT), a natural sesquiterpenoid ketone with anti-inflammatory properties, has unclear effects on ulcerative colitis (UC). This study investigated the protective effect of NKT against dextran sulfate sodium (DSS)-induced UC in mice and its underlying mechanisms. A UC-mouse model was established by DSS administration in BALB/c mice, along with an in vitro coculture system comprising peritoneal macrophages and colonic epithelial cells. The therapeutic effect of NKT was evaluated by monitoring body weight, fecal characteristics, colon length, disease activity index (DAI), and histopathological changes in the colon tissues. Goblet cells were observed by Alcian Blue-Periodic Acid Schiff (AB-PAS) staining; the expression of the tight junction proteins, occludin and ZO‑1, was detected by Western blotting. Network pharmacology was used to predict potential targets and pathways, while immunohistochemistry and Western blotting helped verify the expression of apoptosis- and inflammation-related proteins. The NKT effect on intestinal epithelial cell migration was analyzed using cell coculture and scratch assays. Flow cytometry was used to assess macrophage polarization. NKT significantly alleviated body weight loss, the increase in DAI scores, mitigated colon shortening and histopathological damage in UC mice, and upregulated the expression of ZO‑1 and occludin in the colon tissues. The CMC‑Na control group exhibited insignificant improvements. Further, Caspase-3 and the TNF pathway were predicted to be key targets, wherein NKT intervention downregulated the pro-apoptotic protein Bax, apoptosis-executioner protein Caspase-3, and the inflammatory factor TNF-α, while increasing the anti-apoptotic protein Bcl-2. In vitro experiments and flow cytometry further revealed that NKT promoted the migration of mouse colonic epithelial cells and selectively suppressed M1 macrophage polarization in vitro, respectively. NKT exerted a significant ameliorative effect on DSS-induced UC in mice, and the underlying mechanism may be related to the enhancement of intestinal mucosal barrier function, inhibition of epithelial cell apoptosis, suppression of M1 macrophage polarization, and regulation of inflammatory pathways.
Zhang Q, Hu C, Sun F, Yao J
Therapeutic Prospects of Caulerpin: A Marine-derived Bisindole Alkaloid with Anti-inflammatory and Cardioprotective Potential. Cardiovascular & hematological disorders drug targets | 2026-10-30
Numerous studies have shown the therapeutic potential of caulerpin, an antinociceptive and anti-inflammatory bisindole alkaloid discovered in marine algae, especially members of the genus Caulerpa. In animal studies, the anti-inflammatory effects of caulerpin attenuated the early and late stages of the formalin-induced pain response and decreased nociception caused by acetic acid. Extracts have demonstrated anti-obesity, anti-diabetic, and anti-hypertensive characteristics in earlier studies. Caulerpin exhibited anti-inflammatory properties by lowering the recruitment of inflammatory cells in the carrageenan- and capsaicin-induced peritonitis and ear edema models, as well as reducing inflammation and damage in animal models of ulcerative colitis. Based on the results, it is clear that caulerpin may have useful effects on cardiovascular health because of its anti-inflammatory properties and metabolic pathway regulatory mechanisms. The mechanism of action seems to involve an increase in the anti-inflammatory cytokine IL-10 and a decrease in the inflammatory cytokines TNF-α, IFN-γ, IL-6, and IL-17. Further investigation is required to understand the exact mechanism of action and therapeutic potential of caulerpin in inflammatory and cardiovascular diseases. This review aims to provide a brief overview of the potential therapeutic uses of caulerpin, specifically focusing on its role in the cardiovascular system and inflammation.
Vijayakumar R, Rengaswamy G, Venkatachalam K, Binesh A
DOI: 10.2174/011871529X464286261026045256 | View on PubMed →
Epidemiology & Outcomes (10 papers)
Clinical profiles and management strategies in older adults with mild-to-moderate ulcerative colitis: a multicenter, comparative, real-world study. Intestinal research | 2026-11-11
The growing prevalence of mild-to-moderate ulcerative colitis (UC) among elderly individuals ( ≥60 years) poses unique clinical challenges due to age-related vulnerabilities, while real-world evidence on outpatient management and age-based differences remains limited. This multicenter cross-sectional study recruited 429 patients with mild-to-moderate UC from 47 inflammatory bowel disease centers. A Delphi-developed questionnaire was applied to assess clinical profiles and medication adherence. All statistical analyses were performed using R 4.5.0, with P-value < 0.05 set as the significance level. Older patients had a longer median disease duration (6.0 years vs. 4.0 years; P= 0.001) and a higher proportion with moderate disease activity (60.4% vs. 51.8%; P= 0.029) compared with non-older patients. Diagnostic efficiency, disease extent, and extraintestinal manifestations did not differ between groups. Use of 5-aminosalicylic acid (5-ASA) remained the first-line therapy in both groups, with lower corticosteroid use among older patients (8.8% vs. 16.2%; P= 0.035). Older patients reported higher satisfaction with 5-ASA across several care domains (P= 0.019). Medication adherence was similar across age groups, and adherence analysis identified switching to biologics (odds ratio [OR], 0.31; P= 0.001), 3-4 physician visits for diagnosis (OR, 0.60; P= 0.048), and greater long-term efficacy satisfaction (OR, 0.64; P= 0.049) were associated with better adherence. Older adults with mild-to-moderate UC demonstrate distinct clinical phenotypes and divergent treatment priorities. Timely therapeutic escalation, the diagnostic process, and perceived treatment effectiveness are closely associated with medication adherence. These findings highlight the need for age-adapted management strategies in elderly UC patients.
Gu H, Li C, Liang J, Tian F, Cao X, Li Y, Gu Y, Shen J
Co-existent autoimmune diseases in people with multiple sclerosis and a review on choice of immunotherapy. Immunotherapy | 2026-11-09
Coexisting autoimmune diseases in multiple sclerosis (MS) may influence disease-modifying therapy (DMT) choice, but Indian data remains limited. This study aims to determine the prevalence of co-existent autoimmune disorders in Indian MS patients and assess their impact on DMT selection. This multicentre, cross-sectional observational study included 355 adults with MS evaluated across five Indian neuroimmunology clinics between 2016 and 2026. Comorbidity prevalence was compared against general-population estimates, and DMT utilization was compared between patients with and without autoimmune comorbidities. Fifty-nine patients (16.6%) had an autoimmune disorder, with hypothyroidism (5.9%), rheumatoid arthritis (RA; 2.0%), and type 1 diabetes mellitus (1.4%) being the most common. Prevalences of RA (2.0% vs 0.49%; p = 0.002) and inflammatory bowel disease (IBD; 0.8% vs 0.02%; p < 0.001) were significantly higher than population estimates. Comorbidities shifted treatment: Rituximab use was lower in the comorbidity group (49.2% vs 69.3%; p = 0.003); dimethyl fumarate (22.0% vs 1.4%; p < 0.001) and azathioprine (5.1% vs 0.7%; p = 0.004) were prescribed more frequently. Autoimmune comorbidity occurred in about 1/6 Indian MS patients, with excess RA and IBD relative to population prevalence and an associated shift in DMT selection. Multiple sclerosis (MS) is a long-term condition in which the body’s immune system mistakenly attacks the brain and spinal cord. Some people with MS also have other autoimmune diseases, in which the immune system attacks healthy parts of the body, and these can affect which MS medicines suit them best.We reviewed the data of 355 adults with MS seen at five specialist hospital clinics in India between 2016 and 2026. We looked at which other autoimmune diseases they had and which MS medicines they took, and compared how common these conditions were with the general population.We found that about one in six people with MS (59 of 355, or 16.6%) also had another autoimmune disease. The most common were hypothyroidism, rheumatoid arthritis (RA) and type 1 diabetes. RA and inflammatory bowel disease were more common in people with MS than in the general population, whereas hypothyroidism was less common.The choice of MS medicine also differed. People with another autoimmune disease were less likely to receive rituximab and more likely to receive dimethyl fumarate or azathioprine as treatment for MS.Doctors should therefore look for other autoimmune diseases in people with MS and consider them when choosing treatment. However, because we studied patients at one point in time in specialist centers, we cannot say that one condition causes the other, and our results may not apply to everyone with MS in India. Large scale studies over a longer time period are required to study these effects.
Netterwala A, Garg S, Majumdar P, Bhardwaj S, Kumar S, Javali M, Murgod U, Bannerjee TK, Kamath V, Krishnan P
Fibrotic complications in ulcerative colitis are associated with early and persistent healthcare burden. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver | 2026-11-07
Ulcerative colitis (UC) is traditionally considered a mucosal, non-fibrostenosing inflammatory bowel disease, yet emerging evidence suggests that fibrosis is more clinically relevant in UC than previously recognized. Population-based data describing the risk factors and healthcare burden of fibrotic complications in UC are limited. We conducted a retrospective population-based cohort study using data from Maccabi Healthcare Services, a nationwide insurer-provider. Non-malignant strictures, stenosis, or obstruction post-UC diagnosis were used as a proxy for fibrotic complications. Risk factors were assessed using Cox regression. Patients with fibrotic complications were then matched to controls to compare healthcare resource utilization (HCRU) and treatment patterns. Among 6,944 patients with UC, 100 (1.4%) developed fibrotic complications. Older age at diagnosis (HR [95%CI]=1.81[1.05-3.13] for ages 41-65 and 2.75[1.30-5.80] for >65 vs. 18-40), comorbidities (1.73[1.04-2.88]), and advanced therapy exposure (4.38[2.47-7.74]) were independently associated with increased risk of fibrotic complications, whereas proctitis at presentation was protective (0.49[0.31-0.78]). Patients with fibrotic complications had higher HCRU, medication use, and costs throughout the disease course, evident even before fibrotic complication diagnosis, with a further increase in HCRU post-diagnosis. Fibrotic complications in UC are associated with substantial clinical and healthcare burden, underscoring the need for improved risk stratification, earlier recognition, and further investigation of targeted antifibrotic strategies.
Shapiro I, Igho-Osagie E, Sharman Moser S, Lawlor G, Hoshen M, Liu G, Gazit S, Rieder F, Ben-Tov A
Socioeconomic status and long-term risk of inflammatory bowel disease: a prospective cohort study with mediation analysis. Journal of global health | 2026-11-06
The association of socioeconomic status with incident inflammatory bowel disease and the contribution of lifestyle factors remain unclear. We aimed to comprehensively investigate the association between socioeconomic status (SES) and the risk of inflammatory bowel disease (IBD), and to assess the mediating effect of lifestyle factors in a prospective cohort. We assessed SES using household income, education level, and employment status, and categorised participants into high-, medium-, and low-SES groups using latent profile analysis. We combined lifestyle factors, including smoking, alcohol consumption, diet, physical activity, body mass index, and sleep duration, to calculate a healthy lifestyle score as a mediator. The primary outcome was incident IBD. We used Cox proportional hazards models and mediation analysis to examine associations between SES and incident IBD and to assess the mediation effect. Participants free of IBD at baseline were included (n = 374,507), with a mean age of 55.84 years, of whom 51.5% were female. Overall, 76,292 (20.4%) were classified as high, 197,130 (52.6%) as medium, and 101,085 (27.0%) as low patterns. Over 14.57 years of follow-up, we identified 2381 incident IBD cases, 1703 ulcerative colitis (UC) and 843 Crohn’s disease (CD), with an overall incidence rate of 44.9 per 100,000 person-years. After multivariable adjustment, a high SES pattern was associated with a 45% lower IBD risk compared to low SES (hazard ratio (HR) = 0.55; 95% confidence interval (CI) = 0.48-0.63). Meanwhile, all SES components showed beneficial effects, with higher education level demonstrating the strongest association (HR = 0.58; 95% CI = 0.51-0.65). The combination of high SES and healthy lifestyle conferred the greatest protection (HR = 0.37; 95% CI = 0.29-0.46). Mediation analyses indicated that lifestyle factors explained 11.34-16.50% of the observed association between SES and incident IBD. Similar protective associations were observed for both UC and CD. Healthy lifestyle factors partially explained the association between SES and incident IBD. However, these findings should be interpreted cautiously given the observational design, potential residual confounding, and assumption-dependent mediation estimates.
Zhang Q, Wang Y, Yu S, Zhou Y, Liu S, Li P, Zhang S, Wu S
Hypoxia orchestrates the natural history of inflammatory bowel disease: Mechanisms and therapeutic opportunities.Review Pharmacological research | 2026-11-05
Inflammatory bowel disease (IBD) arises from a dynamic interplay between epithelial dysfunction, immune activation, microbial dysbiosis and tissue remodelling. Although hypoxia was initially regarded as a consequence of intestinal inflammation, it is now recognized as an active regulator of epithelial, immune and stromal responses that coordinate disease progression. Here, we propose that hypoxia acts as a biological organizer linking oxygen sensing to the transition from intestinal homeostasis to chronic inflammation and structural tissue damage. We use this term in a mechanistic rather than a hierarchical sense: oxygen availability is a shared upstream constraint on epithelial, immune, microbial and stromal programmes, not a single initiating event. This review integrates evidence connecting oxygen sensing with epithelial barrier integrity, immunometabolism, microbial ecology and stromal remodelling, with emphasis on advances in single-cell transcriptomics, spatial biology and microbiome research. Physiological low-oxygen gradients support epithelial metabolism, barrier integrity and immune tolerance, whereas persistent inflammatory hypoxia drives oxidative stress, metabolic reprogramming and maladaptive epithelial-immune-microbial interactions. Hypoxia also contributes to spatially distinct epithelial, immune and stromal niches that may sustain chronic inflammation and fibrotic progression. Microbial metabolites, including short-chain fatty acids and succinate, together with iron metabolism and ferroptosis, further link oxygen sensing to tissue injury, adaptation and repair. These findings position hypoxia-responsive signalling as a pharmacologically actionable network rather than a downstream consequence of inflammation. Targeting selected components may promote mucosal healing and limit structural disease progression, although successful translation will require cell- and isoform-selective modulation, adequate tissue exposure and careful assessment of long-term safety.
Luque MVS, Moreno ASA, Angarita-Planchez ME, Múnera-Rodríguez AM, López-Enríquez S, Casado-Jurado D, de Miguel M, Palomares F
Risk of perianal penetrating complications among adult patients with non-penetrating Crohn’s disease initiating advanced therapies: a retrospective cohort study.★ Journal of Crohn’s & colitis | 2026-11
We conducted a retrospective cohort study comparing the risk of perianal penetrating complications with advanced therapies (AT) in patients with non-penetrating Crohn’s disease (CD). Using an administrative claims database (OptumLabs Data Warehouse), we identified adult patients with CD who initiated treatment with tumor necrosis factor (TNF) antagonists, vedolizumab, ustekinumab, IL-23p19 antagonists or Janus kinase (JAK) inhibitors between 2016 and 2022. Patients with any CD-related penetrating complication, abdominal or perianal, during the baseline 1 year and up to 3 months post AT initiation were excluded. We compared on-therapy incidence and risk of developing perianal penetrating complications across different ATs, through multinomial propensity score-based inverse probability weighting. We identified 10 482 patients with non-penetrating CD who initiated TNF antagonists (n = 4463), vedolizumab (n = 2372), ustekinumab (n = 3027), IL-23p19 antagonists (n = 480) and JAK inhibitors (n = 140), of whom 360 (3.4%) developed perianal penetrating complications over a mean follow-up of 18.511.2 months. After adjusting for confounding variables, TNF antagonists (hazard ratio [HR], 0.56 [95% CI, 0.42-0.74]) and ustekinumab (HR, 0.62 [0.46-0.83]) were associated with lower risks of developing perianal penetrating complications compared with vedolizumab. Among advanced therapy-naive patients (n = 8240), TNF antagonists (HR, 0.66 [0.49-0.89]) and ustekinumab (HR, 0.69 [0.48-0.99]) were associated with lower risk of perianal penetrating complications compared with vedolizumab. Among patients with prior AT exposure (n = 2242), TNF antagonists (HR, 0.26 [0.08-0.85]) and ustekinumab (HR, 0.46 [0.30-0.72]) were associated with lower risk of perianal penetrating complications compared with vedolizumab. Among patients with non-penetrating CD starting an AT, TNF antagonists and ustekinumab were associated with a lower risk of developing perianal penetrating complications compared to vedolizumab.
Hupé M, Ahuja D, Yeh KH, Patel SB, Xu R, Vuyyuru SK, Malik TA, Ramos GP, Faubion WA, Ananthakrishnan AN
Treatment patterns and determinants of persistence with advanced therapies in adults with newly diagnosed Crohn’s disease: an interim analysis of an inception cohort registry study (iCREST-CD).★ Journal of Crohn’s & colitis | 2026-11
Multiple advanced therapies are available for the treatment of Crohn’s disease (CD). Treatment patterns in newly diagnosed patients and the factors associated with persistence remain unclear. We present interim results of the iCREST-CD registry describing treatment patterns and persistence with advanced therapies. Patients aged ≥16 years with newly diagnosed CD and who had no prior exposure to advanced therapies were enrolled. Persistence of advanced therapies was estimated using Kaplan-Meier analyses, and associated factors were identified using multivariable Cox proportional hazards models. Persistence was also compared between patients who initiated therapy early or later after diagnosis. Of 672 patients (68.2% male; mean age 29.4 ± 13.1 years), 498 (74.1%) initiated advanced therapy: infliximab (IFX; 121), adalimumab (ADA; 244), ustekinumab (UST; 107), or vedolizumab (VDZ; 26). Advanced therapy was initiated within 1 year of diagnosis in 404 (60.1%). The 36-month treatment persistence rates for IFX, ADA, UST, and VDZ were 77.5%, 75.7%, 79.8%, and 49.0%, respectively. After propensity score adjustment using inverse probability of treatment weighting, the early initiation was associated with greater persistence than delayed initiation, although the difference did not reach statistical significance (hazard ratio, 0.61; 95% confidence interval, 0.35-1.09; P = .067). A high prevalence of early advanced therapy use and a high level of persistence with first-line advanced therapy were identified in this national cohort. Early initiation was associated with greater treatment persistence than delayed initiation, suggesting the potential clinical relevance of earlier advanced therapy use in routine practice. These findings require confirmation in other prospective studies aiming to evaluate early intervention strategies. The study was registered with the University Hospital Medical Information Network Clinical Trials Registry (umin.ac.jp/ctr Identifier: UMIN000032237) prior to initiation.
Shinzaki S, Matsuoka K, Fujii T, Okamoto R, Yamada A, Kunisaki R, Matsuura M, Watanabe K, Shiga H, Takatsu N
Pediatric inflammatory bowel disease in New Zealand study: a 10-year update on national incidence and point prevalence in 2025. Crohn’s & colitis 360 | 2026-10-28
The incidence of inflammatory bowel disease (IBD) in children is increasing worldwide, with high rates previously noted in New Zealand. The incidence and prevalence of pediatric IBD in New Zealand was last delineated in 2015. The aim of this study was to provide updated epidemiological data by delineating the incidence and prevalence of pediatric IBD in New Zealand ten years after the previous assessment. For the incidence cohort, patients younger than 16 years with IBD, diagnosed between January 1, 2025 and December 31, 2025 were identified and information entered into a secure database. Population data were obtained and incidence calculated. To derive the point prevalence, all patients diagnosed with IBD under the age of 16 years on June 30, 2025 were identified and information entered into a secure database. Population data were obtained and prevalence calculated. The incidence of pediatric IBD, Crohn’s disease (CD), ulcerative colitis (UC) and inflammatory bowel disease-unclassified (IBD-U) in New Zealand in 2025 was 8.0, 5.6, 2.0, and 0.4 per 100 000 respectively. The point prevalence of IBD, CD, UC, and IBD-U in children in New Zealand on June 30, 2025 was 33.0, 21.7, 8.1, and 3.2 per 100 000 respectively. The incidence and prevalence of IBD have increased 1.5 times in children in New Zealand since 2015. New Zealand continues to have some of the highest rates of pediatric IBD in the world. Ongoing research is needed to understand factors leading to increasing rates and to ensure appropriate health service provision.
Cherry CTL, Evans HM, Mouat SW, Bishop JR, Roberts AJ, Fireman N, Bhana A, Haszard JJ, Day AS, Lopez RN
Reduced bone mineral density in Southeast Asian children with Crohn’s disease: Prevalence and predictors. Pediatrics and neonatology | 2026-10-24
Reduced bone mineral density (BMD) is an important but under-recognized complication of pediatric Crohn’s disease (CD). Prevalence data from Southeast Asia is limited. We studied the prevalence of reduced BMD and identified its associated risk factors in a multiethnic Southeast Asian children cohort with CD. A retrospective cross-sectional study was conducted involving all children (<18 years) with CD across 10 years in two tertiary centers. Data on demography, clinical characteristics, laboratory parameters, dual-energy X-ray absorptiometry (DXA) reports, and treatment were analyzed. Suboptimal and low BMD were defined as lumbar BMD Z-scores of < -1 and ≤-2, respectively. Of 54 children with DXA scans (male 55.6%, median age at diagnosis 11.5 years), 66.7% had suboptimal and 29.6% had low BMD. 75.9% underwent DXA scans at diagnosis. Reduced BMD was significantly associated with gender, height-for-age Z-score, growth delay, and wPCDAI score. Female gender and severe stunting were independent predictors of low BMD, while higher wPCDAI and lower height-for-age Z-scores were independent predictors of reduced BMD Z-score. A height-for-age Z-score of -2.04 best predicted low BMD. This first Southeast Asian study found a high prevalence of reduced BMD among Malaysian children with CD. Anthropometric measures may help triage at-risk patients for timely investigations and treatment. Incorporating routine BMD screening at diagnosis into clinical care pathways should be considered to enable early intervention and improve long-term outcomes in affected children.
Ser GTZ, Chew KS, Choong CL, Lee WS
Bridging the evidence gap in isolated proctitis: real-world evidence on medical therapies for isolated proctitis-a nation-wide analysis using data of 8346 patients from UK IBD BioResource. Crohn’s & colitis 360 | 2026-10-23
Isolated proctitis (IP) affects a third of patients with ulcerative colitis. The long-term effectiveness of medical therapies in IP is still unclear. To assess the effectiveness of medical therapies in IP. A retrospective observational cohort study using data from the NIHR IBD BioResource registered between April 4, 2016, and January 3, 2025. A total of 8346 patients with IP were included. The probability of treatment escalation from 5-aminosalicylates (5-ASAs) was 11.1%, 21.5%, and 27.3% at 1, 3, and 5 years respectively. Age onset >40 years was associated with a lower risk (hazard ratio [HR] = 0.552, 95% confidence interval [CI]: 0.491-0.621) and presence of extra-intestinal manifestations (EIMs) associated with a higher risk (HR = 1.701, 95% CI: 1.432-2.020) of treatment escalation. The probability of treatment escalation from thiopurines was 14%, 24.4%, and 30.8% at 1, 3, and 5 years respectively. Montreal classification A3 (HR = 0.707, 95% CI: 0.597-0.836) and longer disease duration (HR = 0.983, 95% CI: 0.972-0.995) were associated with a lower risk, while co-diagnosis of EIM indicated a higher risk (HR = 1.513, 95% CI: 1.209-1.894) of treatment escalation. Compared to infliximab, adalimumab (odds ratio [OR] 0.537, 95% CI: 0.416-0.692) and golimumab (OR 0.361, 95% CI: 0.206-0.618) were associated with reduced odds, while anti-integrin exposure was associated with an increased odds of treatment response (OR 2.033, 95% CI: 1.529-2.720). Among the available advanced therapies evaluated, anti-integrin therapy was associated with the highest treatment persistence and response rates in this real-world cohort of IP. Further clinical trials are warranted in IP.
Yan K, Vuyyuru SK, Radford S, Taylor A, Sahin B, Famokunwa B, Moran GW
AI & Machine Learning (7 papers)
Representation geometry and task performance in vision-language modeling for computed tomography enterography. Journal of medical imaging (Bellingham, Wash.) | 2026-11-10
Computed tomography (CT) enterography is central to inflammatory bowel disease evaluation, but optimal representation choices for vision-language learning on this volumetric modality are unclear. We establish baseline performance and quantify how aggregation, slice encoding, and retrieval context affect classification, retrieval, and report generation. We fine-tuned vision-language models on abdominal CT enterography with parameter-efficient adapters and compared (i) mean versus attention pooling of slice embeddings, (ii) multiwindow red-green-blue Hounsfield-unit encoding versus multiplanar sampling for added spatial coverage, and (iii) report generation with versus without retrieval-augmented generation (RAG). A three-teacher pseudolabel framework enabled evaluation without expert annotations. Classification and retrieval comparisons used three training seeds. Mean and attention pooling achieved the same mean three-class disease classification accuracy (55.7%; standard deviations of 2.0 and 2.4 percentage points) at the largest low-rank adaptation capacity. Neither consistently outperformed the other at matched capacity with central sampling. Sixteen slices at 20% to 80% had higher classification accuracy than 8 slices, 32 slices, and 10% to 90% sampling in all three seeds for both pooling methods. The tested multiplanar configurations had lower classification accuracy. For report generation, fine-tuning without retrieval performed at prevalence-matched chance for within-1 report-label agreement (70.4% versus 71.0% random). RAG improved within-1 report-label agreement by 7 to 14 points over chance and reduced ordinal mean absolute error from 0.98 to 0.80-0.89. Slice sampling and tissue-contrast-focused encoding affect performance in CT enterography vision-language systems, and RAG improved report-label agreement over the fine-tuned baseline. These results provide initial baselines and practical guidance for multimodal learning in volumetric CT.
Minoccheri C, Wittrup E, Najarian K, Stidham R
Cross-Sectional Association between Fiber Intake and Gastrointestinal Inflammation is Dependent on FUT2 Secretor Status in Healthy Adults. The Journal of nutrition | 2026-11-10
Gut microbes consume mucins in the absence of dietary fermentable fiber. People with non-secretor alpha-1-2-L-fucosyltransferase 2 (FUT2) genotypes produce gastrointestinal (GI) mucins that lack terminal fucose and have increased risk for inflammatory bowel disease. This study aimed to determine whether associations between fiber intake and subclinical GI inflammation and/or microbiome function are modified by FUT2 genotype in healthy adults. We assessed interactions between fiber intake, FUT2 genotype, and GI inflammation markers in a cross-sectional observational study of healthy adults. Participants with 24-h dietary recalls and food frequency questionnaires to characterize recent and habitual diet, respectively, and fecal samples, plasma samples and/or shotgun metagenomes (n=297) were included in this analysis. Differences in microbiome composition between secretors and non-secretors were analyzed using PERMANOVA and machine learning. A custom-designed TaqManTM probe was used to genotype a single nucleotide polymorphism (rs601338) to determine secretor status. ELISA was used to measure fecal calprotectin, myeloperoxidase, and neopterin, as well as plasma lipopolysaccharide binding protein. Short-chain fatty acids (SCFAs) were measured in fecal samples. Relationships between fiber intake, FUT2 genotype and outcomes were analyzed using linear mixed effect models. Higher energy-adjusted total recent fiber, total habitual fiber, and soluble fiber intake was associated with lower calprotectin levels in secretors, but not in non-secretors. Overall microbiome composition did not differ by secretor status. However, the ratio of mucin-degrading to plant-degrading enzymes, Muc2Plant, in the gut microbiome was positively associated with increased fecal calprotectin in secretors, but not in non-secretors. There was no interaction between dietary fiber intake, the FUT2 genotype, and fecal SCFAs. The association of higher dietary fiber intake with lower subclinical GI inflammation and lower mucin-degrading enzymes was observed in secretors, but not in non-secretors. Clinical trials in nutrition are needed to determine if non-secretors are less responsive to dietary fiber.
Bouzid YY, Oliver A, Blecksmith SE, Wilson SMG, Alkan Z, Huang L, Bennett BJ, Kable ME, Stephensen CB, Lemay DG
Compliance-by-Design in an AI-Enabled Platform for Early Crohn Disease Interception: A Viewpoint. Journal of medical Internet research | 2026-11-09
AI-enabled digital medicine platforms in Europe are developed within overlapping rules for personal data, medical devices, AI, clinical research, health data access, and health technology assessment. This viewpoint represents the authors’ experience and interpretation from the preimplementation phase of INTERCEPT, an Innovative Health Initiative consortium that plans to validate biomarkers and develop a blood-based risk score for early Crohn disease interception. It does not report original empirical research, a systematic regulatory review, a deployed platform, or a validated AI model. Our aim is to explain how compliance-by-design can be translated into an auditable governance architecture and to identify what still requires scientific evaluation. We advance 3 messages. First, governance must begin with intended purpose and boundary mapping: a digital platform may contain research, operational, and medical device software functions, and conformity of one module cannot be inferred for the platform as a whole. Second, overlapping obligations can be operationalized through 5 linked controls: modular responsibility and change control, federated data governance, traceable AI life cycle management, consent and participant rights orchestration, and a common cross-border governance core with local adaptations. Third, compliance is not a surrogate for model validity, clinical benefit, trust, scalability, or market access. Before clinical deployment, planned AI components require prespecified labels and cohorts, leakage prevention, missing data and imbalance strategies, calibration, subgroup assessment, external validation, human factors evaluation, and postdeployment algorithmovigilance. A hypothetical biomarker risk score update illustrates how the 5 controls interact. INTERCEPT is informative because it combines cross-border biomarker research, planned predictive analytics, and heterogeneous institutional settings while key design decisions remain modifiable. Its contribution is nevertheless conceptual: the proposed framework is a testable governance hypothesis, not evidence of implementation success. Prospective studies should compare it with alternative governance models and assess safety, workload, participant experience, evidence generation, and regulatory performance.
Scaldaferri F, Puca P, Fiorelli E, Bosmans J, Vesely R, D’Haens G, Colombel JF, Torres J, Gasbarrini A, Cesario A
Interpretable machine learning applied to high-dimensional salivary proteomics in pediatric inflammatory bowel diseases.★ Inflammatory bowel diseases | 2026-11-09
Inflammatory bowel diseases (IBDs), including Crohn’s disease (CD), ulcerative colitis (UC), and inflammatory bowel disease unclassified (IBD-U), are chronic inflammatory disorders of the gastrointestinal tract. Current methods for classification and longitudinal monitoring are invasive, expensive, and often delayed, limiting timely diagnosis and management. This proof-of-concept study reports the first application of high-dimensional salivary proteomics integrated with interpretable artificial intelligence/machine learning (ML) to define a minimal protein signature for pediatric IBD classification with the ultimate goal of informing therapeutic decision-making. Unstimulated saliva from pediatric CD, UC, and IBD-U patients was analyzed using Alamar Biosciences’ NULISAseq 250 Protein Inflammation Panel. Logistic regression with recursive feature elimination identified a candidate minimal discriminative signature. Performance was further assessed using follow-up samples. SHAP (SHapley Additive exPlanations) quantified patient-specific protein contributions and assessed biological similarity of IBD-U to CD and UC. Differential abundance analysis between UC and CD revealed 53 significantly different proteins. ML identified a 14-protein signature comprising chemokines/cytokines (CCL1, IFNA1-IFNA13, IL12p70, IL34, TNFSF11/RANKL), receptors/ligands (CD40LG, ICOSLG, IL1R2, IL17RA), structural/tissue-remodeling proteins (CD93, GFAP, SPP1), and growth factors/immune modulators (GDF2, GZMA). The proposed model achieved 97.5% balanced accuracy in first-visit pilot samples and 80.2% with matched follow-up samples. SHAP revealed patient-specific drivers and suggested biological alignment of IBD-U cases toward CD- or UC-like profiles. This first-in-field integration of salivary proteomics with interpretable artificial intelligence/ML demonstrates that accurate, noninvasive classification of pediatric IBD is possible using minimal biomarker sets. This approach establishes a scalable framework for future longitudinal monitoring and supports earlier and more precise therapeutic interventions.
Rupp BT, Reyna J, Giunta A, Weaver T, Chason K, Liu J, Gulati AS, Byrd KM
The application of an artificial intelligence-enhanced virtual reality cognitive behavioral therapy tool is feasible and acceptable in patients with inflammatory bowel disease: A multicenter mixed methods pilot study.★ Inflammatory bowel diseases | 2026-11-05
Patients with inflammatory bowel disease (IBD) frequently experience anxiety, pain, and reduced quality of life. Cognitive behavioral therapy (CBT) is effective for anxiety, but access may be limited. We evaluated the feasibility and explored the potential clinical impact of an artificial intelligence-powered virtual reality CBT-based application (XAIA [eXtended Reality Artificially Intelligent Ally]) in patients with IBD. This was a multicenter, mixed-methods pilot study recruiting adults with IBD from the University of Chicago and Cedars-Sinai medical centers. Participants completed a single 30-minute session with the XAIA conversational avatar. Pain and anxiety were measured before and after the session using a visual analog pain scale and State-Trait Anxiety Inventory, respectively. Semi-structured interviews were conducted after the session to assess acceptability. Quantitative analysis was completed using paired t tests, and interview transcripts underwent thematic analysis. Thirty-four participants (median age 34 years, 71% women, 59% with Crohn’s disease) participated in this study. Qualitative analysis revealed high acceptability, with participants reporting feelings of safety, validation, and improved coping. Participants valued the immersive environment, conversational avatar, and ability to discuss sensitive topics without judgment. As an exploratory outcome, participants reported a statistically significant improvement in pain (-0.46; P = .011) and anxiety (-10.65; P < .001) immediately following a single session. A single artificial intelligence-driven virtual reality CBT-based session in patients with IBD was feasible and well accepted and demonstrated preliminary evidence for acute reductions in pain and anxiety scores. Immersive digital behavioral health interventions may represent a scalable adjunct to traditional mental health support among adults with IBD. The use of an artificial intelligence–guided, cognitive behavioral therapy–based virtual reality program in patients with inflammatory bowel disease was found to be engaging with improvement in anxiety and pain scores. This may support immersive digital therapy in this population.
George AT, McDermott AR, Bedell AR, Clark AL, Mehra M, Liran O, Anand R, Chernoff R, Capucci LC, Spiegel BMR
Authentic Sources, Potentially Unsafe Conclusions: Evidence Traceability Does Not Ensure Clinical Reliability in Retrieval-Augmented Generation for Perioperative IBD. Journal of multidisciplinary healthcare | 2026-11-01
Retrieval-augmented generation (RAG) is increasingly used to reduce hallucination in medical large language models (LLMs), but authentic retrieval does not necessarily ensure clinically correct output. We evaluated whether full-text-enriched RAG improves the clinical reliability of locally deployed models for perioperative inflammatory bowel disease (IBD) question answering. We constructed a locally deployed full-text IBD perioperative knowledge base and a 50-question high-difficulty benchmark. Two 8B models (Qwen3-VL-8B and DeepSeek-R1-Distill-Llama-8B) were evaluated under matched no-retrieval and RAG conditions. Three physicians independently scored clinical accuracy, patient safety, and faithfulness under a source-blinded, format-homogeneous protocol. Evidence traceability was assessed objectively by verifying all retrieved PubMed identifiers (PMIDs) against PubMed. All retrieved PMIDs existed in PubMed (236 verifications; 187 unique), confirming source-existence authenticity at the retrieval layer. RAG significantly improved Qwen3 accuracy (Δ=+0.44, P<0.001) but not DeepSeek accuracy (Δ=+0.21, P=0.09), and the model-by-retrieval interaction for accuracy was not significant. Patient safety showed no reliable benefit. Faithfulness decreased significantly with RAG on Qwen3 (Δ=-0.24, P<0.001), with a significant model-by-retrieval interaction. Inter-rater reliability was excellent (ICC 0.86-0.93). PubMed-based retrieval achieved source-existence authenticity but did not consistently improve clinical correctness or safety. Authentic references could accompany incorrect or unsafe conclusions, indicating that evidence traceability and clinical reliability should be evaluated separately. Additional model-external safety mechanisms may be warranted in high-risk settings but require independent validation.
Hu W, Cai Y, Sun L, Huang B
Targeting the IL-23-IL-23R Interface with Small Molecules: Challenges, Opportunities, and Emerging Strategies. Mini reviews in medicinal chemistry | 2026-10-30
Interleukin-23 (IL-23) is a validated therapeutic driver in psoriasis and inflammatory bowel disease, and selective IL-23p19 antibodies have established a high efficacy benchmark for pathway inhibition. Interest has therefore expanded toward oral, non-antibody approaches, including IL-23R-targeting macrocyclic peptides and conventional low-molecular-weight compounds. Direct antagonism of the IL-23p19-IL-23R interface is attractive because it acts upstream of intracellular JAK2/TYK2 signaling and is structurally separated from the p40-IL-12Rβ1 interaction shared with IL-12. The principal challenge is medicinal-chemical: the orthosteric site is a dynamic proteinprotein interaction surface with limited constitutive pocket character. This Mini-Review focuses on the evidence relevant to drug discovery rather than reiterating pathway biology. We distinguish experimentally validated interface binders from computationally prioritized candidates, summarize potency, selectivity, assay format and development status where available, and discuss lessons from program attrition. Recent advances include an induced orthosteric pocket on IL-23p19, live-cell competition pharmacology, highly potent oral IL-23R peptides, and early small molecule hits supported by cellular assays. Computational docking, molecular dynamics, MM/GBSA, QSAR, and AI-assisted design can enrich hypotheses but do not, by themselves, establish direct binding, selectivity, pharmacokinetics, or safety. The key unresolved question is whether a classical small molecule can demonstrate direct target engagement at this challenging interface while achieving sufficient potency, pathway selectivity, and drug-like exposure to compete with advanced biologic and peptide modalities.
Vu TT, Thai KM, Mai QM, Nguyen NL, Tran QH, Tran TT, Dao TT, Le MT
DOI: 10.2174/0113895575509269261023101541 | View on PubMed →
Surgery & Complications (7 papers)
Pulmonary consolidations with mild FDG uptake in a patient with Crohn’s disease.Case report Breathe (Sheffield, England) | 2026-11-10
Rapid on-site evaluation during cryobiopsy may provide valuable real-time diagnostic clues in organising pneumonia, helping distinguish non-neoplastic inflammatory processes from malignancy in patients presenting with persistent pulmonary consolidations https://bit.ly/3RA2Hfz.
Poletti V, Petrarulo S, Balzano M, Oldani S, Piciucchi S, Ravaglia C
Incidence of Colorectal Cancer After Endoscopic Mucosal Resection: A Multicenter Electronic Health Record Cohort Study.Multicenter study Journal of gastrointestinal cancer | 2026-11-07
Endoscopic mucosal resection (EMR) is widely used for large and complex colorectal lesions and offers a less invasive alternative to surgery. Although adenoma recurrence after EMR has been described in procedural cohorts, real-world estimates of subsequent colorectal cancer (CRC) diagnoses after EMR across multicenter electronic health record (EHR) systems remain limited. We conducted a retrospective cohort study using the TriNetX US Collaborative Network. Patients aged 40 years or older who underwent colonoscopy or sigmoidoscopy with EMR between January 1, 2016 and January 1, 2017 were included. Patients with Crohn’s disease, ulcerative colitis, familial adenomatous polyposis, or CRC recorded on or before the index EMR date were excluded. The primary outcome was incident CRC, defined by ICD-10-CM codes C18, C19, and C20, assessed from January 1, 2018 through December 31, 2021 after a one-year washout period. Incidence rates are reported per 1,000 person-years with exact Poisson 95% confidence intervals (CIs). A sensitivity analysis was restricted to patients aged 50-75 years at index EMR. Among 3,081 eligible patients, the mean age was 62.9 ± 8.89 years and 52% were female; 2,735 were at risk at the start of follow-up. Twenty-two incident CRC diagnoses occurred over 10,187.8 person-years, an incidence of 2.16 per 1,000 person-years (95% CI, 1.35-3.27). Each calendar year contained 10 or fewer events, so annual rates could not be estimated. Incidence was 2.54 (95% CI, 1.31-4.44) in males and 1.83 (95% CI, 0.88-3.36) in females. In the 50-75-year sensitivity cohort, 19 events occurred over 8,894.8 person-years (2.14 per 1,000 person-years; 95% CI, 1.29-3.34). During years 1-5 after index EMR, repeat EMR occurred in 119 patients (3.9%), colorectal surgery in 28 (0.9%), and subsequent colorectal polyp diagnoses in 1,321 (42.9%); no ESD procedures were identified. CRC diagnoses after EMR were uncommon in this multicenter EHR cohort, occurring at about 2 per 1,000 person-years. Event counts were too small to estimate annual trends or to compare incidence reliably across race and ethnicity groups. Studies linking EHR data to endoscopy and pathology reports are needed to identify preventable cancers after EMR.
Eldesouki MH, Elfert K, Ibrahim EA, Youssef MY, Shaukat A, Thakkar S
E3 ubiquitin ligase WWP1 aggravates intestinal inflammation in CD‑like colitis: insights into KLF5 ubiquitination‑mediated NF‑κB signaling regulation. Journal of molecular histology | 2026-11-06
The expression and function of E3 ubiquitin ligase WWP1, as well as the post-translational modification of transcription factor KLF5, have rarely been systematically characterized in Crohn’s disease (CD). We established a TNBS-induced CD-like colitis mouse model and an LPS-stimulated intestinal epithelial cell model. Histopathological staining, Western blot, qPCR and immunofluorescence were used to detect the expression and distribution of WWP1, KLF5 and NF-κB pathway-related proteins in colon tissues. Co‑immunoprecipitation (Co‑IP) and ubiquitination‑related signal assays were performed to examine protein co‑precipitation and ubiquitin‑associated signals for KLF5. CCK-8, ELISA, qPCR and Western blot were applied to assess cell viability, inflammatory cytokine secretion and NF-κB activation. A KLF5 overexpression rescue experiment was conducted to indicate the regulatory relationship between WWP1 and KLF5. In colonic tissues of colitis mice, WWP1 expression was increased to 3.46-fold, while KLF5 expression was decreased to 0.47-fold compared with controls. The levels of pro-inflammatory TNF-α and IL-6 were elevated to 2.81-fold and 3.06-fold, accompanied by noticeable NF-κB pathway activation. Co‑IP assays detected both proteins within immunoprecipitated complexes. WWP1 overexpression was accompanied by altered KLF5 ubiquitination signals, changes in KLF5 protein abundance, and exacerbated LPS‑induced inflammation, whereas ectopic KLF5 overexpression partially mitigated this pro‑inflammatory phenotype. Immunofluorescence suggested the co-localization of WWP1 and KLF5 in colonic mucosal cells of mouse colon tissues. This study suggests that WWP1 may aggravate intestinal inflammation in CD‑like colitis through potential modulation of KLF5, accompanied by downstream changes in NF‑κB signaling activation. This work provides additional mechanistic insights into CD‑like colitis and identifies a potential mediator for further pre‑clinical exploration.
Fang X, Deng H, Li M
Diagnostic Delay and Intestinal Surgery in Crohn’s Disease: A Retrospective Observational Study in a Peruvian Tertiary Hospital. Clinical and experimental gastroenterology | 2026-11-05
Diagnostic delay in Crohn’s disease has been associated with adverse outcomes, including intestinal surgery. Evidence from Latin American tertiary referral settings is limited. We evaluated the association between diagnostic delay and Crohn’s disease-related intestinal surgery in a Peruvian national referral hospital. This retrospective observational analytical study included adults with confirmed Crohn’s disease followed at Hospital Nacional Edgardo Rebagliati Martins, Lima, Peru, between April 2020 and February 2025. Patients with complete clinical information, including documented diagnostic-delay categories and intestinal surgery status, were included. Diagnostic delay was categorized as >12 versus ≤12 months. Logistic regression estimated crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs). The cohort included 47 patients; mean age was 50.0 ± 20.7 years, 55.3% were male, and 53.2% had undergone intestinal surgery. Overall, 29.8% had diagnostic delay >12 months; this was documented in 44.0% of patients with surgery versus 13.6% without surgery. Diagnostic delay >12 months was associated with higher odds of surgery in crude analysis (OR 4.98; 95% CI 1.17-21.24; p=0.030). After adjustment, the association remained positive but imprecise (aOR 3.97; 95% CI 0.87-18.15; p=0.075). Diagnostic delay >12 months was more frequent among patients with Crohn’s disease-related intestinal surgery, while the adjusted estimate remained positive but imprecise. These findings highlight the potential clinical relevance of diagnostic delay and warrant confirmation in larger prospective studies.
Arce-Huamani MA, Cárdenas-Vela I, Abad-Núñez J, Cervera-Caballero L, Castillo-Contreras O, Alcarraz-Castillo A, Herrera-Castillo ED, Vallejo-Jaime MD
Microbial and antimicrobial resistance signatures differentiate healthy and inflamed ileal pouches in patients with ulcerative colitis.★ Journal of Crohn’s & colitis | 2026-11
Fecal microbiota transplantation (FMT) from healthy donors with a normally functioning colon has limited clinical effect in the treatment of chronic pouchitis. However, a normally functioning ileal pouch-anal anastomosis (IPAA) physiology differs from individuals with a healthy intact colon. We aimed to investigate the microbial characteristics of patients with a normally functioning IPAA (HealthyPouch) compared with chronic pouchitis (SickPouch), ulcerative colitis (UC), and a healthy intact colon microbiome (NormalGut). Furthermore, we investigated how repeated antibiotic use influences antimicrobial resistance on a bacterial genome level. Fecal samples from 190 participants were collected; HealthyPouch (n = 38), SickPouch (n = 37), UC (n = 23), and NormalGut (n = 92) and sequenced with Illumina and taxonomically profiled. Samples from HealthyPouch, SickPouch, and NormalGut were also long-read sequenced using Oxford Nanopore Technologies for reconstruction of 12 282 metagenome-assembled genomes (MAGs). DNA methylation motifs were used for plasmid-host association. The HealthyPouch microbiome is distinct from both the UC, NormalGut, and SickPouch microbiome. Escherichia coli MAGs in the SickPouch (n = 21) microbiome had significantly higher co-occurring ciprofloxacin resistance mutations in the gyrA and parC genes, compared to both HealthyPouch (n = 26; BH adjusted P < .05) and NormalGut (n = 40; BH adjusted P < .05). Based on DNA methylation pattern, three plasmids were associated with E. coli carrying extended-spectrum beta lactamase genes. HealthyPouch microbiota differs from NormalGut microbiota, and could therefore be more appropriate for FMT treatment of chronic pouchitis. The association between E. coli and resistance gene-carrying plasmids underscores the importance of integrating plasmid analysis into metagenome-based approaches for personalized antibiotic treatment and resistance monitoring.
Dall SM, Møllekær AH, Kousgaard SJ, Jakobsen SS, Larsen L, Sørensen B, Thorlacius-Ussing O, Albertsen M
Value of non-contrast magnetic resonance imaging for diagnosis of perianal fistulas in Crohn’s disease.★ Journal of Crohn’s & colitis | 2026-11
To compare non-contrast (NC)-MRI and contrast-enhanced (CE)-T1-weighted imaging (T1-WI) for the detection and characterization of perianal fistulizing Crohn’s disease (PFCD). This Institutional Review Board-approved retrospective study included patients with Crohn’s disease (CD) who underwent pelvic MRI (T2-WI, diffusion-weighted imaging [DWI], pre and post-contrast T1-WI) from 10/2021 to 12/2022. Two independent observers assessed presence and severity of perianal disease (St. James Criteria) and abscesses (presence/size) in 2 separate sessions: NC-MRI (T2-WI, DWI, pre-contrast-T1-WI) and CE-MRI (NC-MRI + post-contrast-T1-WI) separated by 6 weeks. Agreement between modalities was evaluated using weighted Cohen’s kappa. Performance of NC-MRI was assessed against CE-MRI as the reference standard. One hundred and forty-five patients (M/F 92/53, mean age 36.2 ± 15.1 years) were included. On NC-MRI, an index fistula was detected in 115/145 patients (grade 1 [n = 55]/grade 2 [n = 15]/grade 3 [n = 16]/grade 4 [n = 33]/grade 5 [n = 6]). On CE-MRI, an index fistula was detected in 117/145 patients (grade 1 [n = 36]/grade 2 [n = 39]/grade 3 [n = 8]/grade 4 [n = 29]/grade 5 [n = 5]). An abscess was detected on NC-MRI in 53 patients (37%) (mean size = 3.3 cm) and on CE-MRI in 63 patients (43%) (mean size = 3.0 cm). There was fair-to-substantial agreement between NC-MRI and CE-MRI (range, 0.46 [presence of secondary tracts] to 0.87 [presence of index fistula]), except for secondary fistula length (no agreement, kappa = 0.008). Compared to CE-MRI, NC-MRI demonstrated a sensitivity/specificity/PPV/NPV/accuracy of 0.96/0.93/0.98/0.84/0.95 for index fistula detection and 0.77/0.95/0.92/0/84/0.87 for abscess detection. NC-MRI has high agreement with CE-MRI for index perianal fistula and abscess detection with clinical feasibility in CD patients. CE-MRI had added value for assessment of complex PFCD, including secondary fistulas and tracts. NC-MRI had high agreement with CE-MRI for detecting perianal fistulas and substantial agreement for grading. CE-MRI has added value in diagnosing complex perianal disease. NC-MRI of the pelvis is a reasonable alternative for perianal fistula detection and grading for patients who cannot receive contrast or for potentially abbreviated exams.
Lewis S, Ahluwalia A, Landis D, Altinmakas E, Kirsner A, Yu R, Doucette J, Wong SY, Colombel JF, Taouli B
Risk factors of short-term colectomy following Janus kinase inhibitor therapy in acute severe ulcerative colitis: a systematic review and meta-analysis of individual-level data from real-world studies. Crohn’s & colitis 360 | 2026-10-23
Emerging evidence supports the use of Janus kinase inhibitors (JAKi) in acute severe ulcerative colitis (ASUC). However, risk factors associated with non-response and the need for short-term colectomy in ASUC patients treated with JAKi remain poorly understood. We conducted a systematic review and individual-level data meta-analysis of real-world studies evaluating tofacitinib or upadacitinib for the treatment of ASUC. The primary and secondary outcomes were colectomy within 30 days and 12 weeks, respectively. Generalized linear mixed-effects models were used for univariable and multivariable analyses to estimate odds ratios (ORs). A stratified Cox proportional hazards model was used to assess colectomy-free survival. Twenty-three studies with 145 patients were included (69.0% treated with tofacitinib, 31.0% with upadacitinib). The overall colectomy rate was 13.1% within 30 days and 20.5% within 12 weeks. In univariable analyses, prior exposure to anti-tumor necrosis factor (TNF) therapy before ASUC hospitalization was statistically significantly associated with lower odds of colectomy within 30 days (OR 0.44, P = .006) and 12 weeks (OR 0.51, P = .008). Prior anti-TNF exposure remained significantly associated with lower odds of colectomy in multiple multivariable analyses. No other clinical or laboratory variables were significantly associated with primary/secondary outcomes. Prior anti-TNF exposure before hospitalization is associated with lower short-term colectomy rates in ASUC patients treated with JAKi. Our findings highlight the need for future studies to optimize the position of JAKi in the ASUC management algorithm and to identify novel predictive biomarkers to advance precision medicine strategies.
Zou Y, Fudman DI, Bishu S, Berinstein JA, Burstein E, Boktor M, Yin J
Biomarkers & Precision Medicine (6 papers)
IBD is associated with species-specific changes in gut microbial gene diversity. mSystems | 2026-11-09
Intra-species genomic variation provides the raw material for natural selection and can reflect the recent diversification history of microbial populations. Environmental stress may be regarded as the ultimate accelerator of the evolutionary process, especially for microorganisms, which can alter their DNA if presented with nutrient limitation, toxins, or pathogen attack. Chronic intestinal inflammation, as in inflammatory bowel disease (IBD), represents prolonged environmental stress for gut commensal bacteria, bringing many enteric species down to undetectable levels. However, it remains unclear how microbes that colonize IBD patients actually respond to IBD-associated stressors and whether stress-driven bacterial dynamics may be identified at the population level from the bacterial gut metagenome. To investigate IBD-associated strain-level population dynamics, we performed metagenomic analyses focusing on measuring within-individual bacterial diversity for a panel of gut commensals present across IBD patients and Controls. First, we found species-specific differences in genome-level bacterial diversity. Then, we found that certain genes and functions may harbor different levels and kinds of genetic divergence within the same species across IBD patients and Controls. Functions that were enriched in IBD with both neutral divergence and functional divergence were associated with motility and iron-scavenging, among others. These results may point toward functions that are under selection in the context of IBD stress and could inform future mechanistic work, exploring previously unknown routes of bacterial diversification and adaptation to stress in the gut microbiome. Inflammatory bowel disease (IBD) is characterized by profound alterations in the gut microbiome composition, and most research so far has focused on changes in species-level abundance to understand gut microbiome contributions to disease dynamics. However, investigating strain-level variation has the potential to uncover previously unknown factors underlying bacterial persistence during gut inflammation, hence revealing key aspects driving gut dysbiosis. Here, we showed that IBD is associated with species-specific changes in gut microbial population-level genetic diversity and identified individual genes and functions that seem to harbor differential genetic diversity within IBD-associated strains. More broadly, our results highlight how intra-species population- and gene-level diversity could be used as sensors of environmental stress in the gut microbiome, and further studies could follow up on the functions highlighted in this work to establish causal links between gut inflammatory conditions and processes of bacterial adaptation to stress.
Mazzoni C, Yassour M
Epigenetic and Post-Transcriptional Regulation of Autophagy in Inflammatory Bowel Disease.Review Gastroenterology research and practice | 2026-11-08
Inflammatory bowel disease (IBD), principally comprising Crohn’s disease (CD) and ulcerative colitis (UC), encompasses chronic immune-mediated inflammatory disorders of the gastrointestinal tract. Genome-wide association studies have identified hundreds of susceptibility loci associated with IBD. Recent studies have highlighted the critical importance of autophagy in maintaining intestinal epithelial homeostasis, regulating host-microbiota interactions, coordinating immune responses and restricting microbial pathogens. Furthermore, emerging evidence indicates that classical epigenetic mechanisms and post-transcriptional regulators may influence autophagy-related pathways in IBD and thereby shape intestinal inflammatory responses. This review critically evaluates current evidence linking epigenetic and post-transcriptional regulation to autophagy in IBD, distinguishes established mechanisms from indirect associations and discusses their mechanistic and translational implications.
Liu Y, Jiang W, Zhou J, Xun F, Li H, Li Y, Zhang J, Qian Y, Wang H
Response to Letter “Visceral adiposity in pediatric Crohn disease: phenotype or disease-activity biomarker?”.Letter★ Inflammatory bowel diseases | 2026-11-06
Abstract not available.
Thangarajah D, Chappell K, Burtt AH, Frost G, Fell JME
Open-IBD: protocol for a longitudinal multi-omics inception cohort in inflammatory bowel disease. BMJ open gastroenterology | 2026-11-04
The clinical course of inflammatory bowel disease (IBD) is highly heterogeneous, yet the biological mechanisms underlying this variability, along with robust predictive biomarkers of disease course and treatment response, remain elusive. Most existing multi-omic cohorts recruit patients after IBD diagnosis and following therapeutic exposure, limiting the ability to distinguish between primary disease biology and downstream consequences of chronic inflammation and/or treatment. There is, therefore, a critical unmet need for large-scale, treatment-naïve inception cohorts integrating deep clinical phenotyping with longitudinal multi-omic profiling from the point of IBD diagnosis. Open-IBD is a prospective, multicentre UK inception cohort study recruiting up to 2000 adults referred with suspected IBD, prior to diagnosis and initiation of IBD-specific therapy. Baseline assessment includes detailed clinical metadata collection, patient-reported outcome measures and collection of blood, stool and intestinal biopsy samples. 1000 participants subsequently diagnosed with IBD will be followed for up to 48 months, with repeated clinical assessments, questionnaires and biosampling. Participants not diagnosed with IBD will form a symptomatic control cohort with longitudinal clinical record review. Multi-omic analyses will include human genetics, single-cell transcriptomics of blood and intestinal tissue, stool and intestinal mucosal microbiome characterisation, metabolomics and proteomics. Integrated longitudinal clinical and multi-omic datasets will be generated to characterise early-stage treatment-naïve IBD, identify biomarkers associated with long-term outcomes and nominate causal factors driving IBD pathophysiology. Ethical approval has been obtained from the Wales Research Ethics Committee 1 (24/WA/0338). All participants provide informed consent before enrolment. Recruitment is ongoing. Study findings will be disseminated through peer-reviewed publications, presentations at scientific meetings and lay summaries. ISRCTN15535639.
Mulligan RJ, Cotobal Martin C, Allerton DM, Strickland M, Bibby I, Fachal L, Watson H, Bates G, Beck LC, Ahmad T
Azelaic Acid Mediates the Protective Effect of Lactiplantibacillus plantarum F1m against Colitis via PPARγ Activation. Journal of agricultural and food chemistry | 2026-11
Ulcerative colitis (UC) is a chronic inflammatory bowel disease with a high recurrence risk. Although probiotics show promise for UC treatment, the underlying mechanisms remain incompletely understood. Herein, we found that Lactiplantibacillus plantarum F1m, isolated from yak yogurt, alleviated dextran sulfate sodium (DSS)-induced colitis in mice, improving symptoms, restoring intestinal barrier function, and alleviating gut microbiota dysbiosis. F1m reversed DSS-induced phylum-level changes by increasing Bacteroidota and decreasing Bacillota, and enriched Faecalibaculum and Akkermansia at the genus level. Mechanistically, F1m suppressed the NF-κB and ERK/MAPK pathways while activating PPARγ signaling. Metabolomics revealed elevated azelaic acid (AzA) levels in F1m-treated mice, positively correlated with the abundances of Bifidobacterium bifidum, Bifidobacterium pluvialisilvae, and Methanobrevibacter smithii. Furthermore, AzA was identified as a microbiota-derived PPARγ ligand, and exogenous AzA alleviated colitis in a PPARγ-dependent manner. Collectively, these findings indicate that F1m enhances AzA production by modulating gut microbiota, thereby protecting against colitis via PPARγ activation.
Jia D, Han Y, Li Z, Zhang X, Fu Y, Duo H, Sheng X, Guan G, Yin H, Li Y
Ulcerative colitis imaging via a ratiometric fluorescent probe with large emission shift for SO2 sensing. Talanta | 2026-10-31
Sulfur dioxide (SO2) serves as a gaseous signaling molecule that exerts pivotal regulatory functions in diverse physiological and pathological processes and has emerged as a novel gaseous biomarker associated with multiple inflammatory and hepatic diseases. Ulcerative colitis (UC), a diffuse inflammatory bowel disease primarily affecting the colonic mucosa, manifests as chronic inflammation. However, direct ratiometric visualization of SO2 in UC lesions has remained challenging due to the scarcity of ratiometric fluorescent probes with large emission shifts suitable for in vivo imaging. Herein, we present SL, a ratiometric fluorescent probe that reports SO2 via analyte-induced dual-emission rearrangement with a large spectral shift. Using SL, we captured dynamic SO2 signals at the cellular level and visualized endogenous SO2 changes in UC mice. These findings demonstrate that SL enables the examination of SO2 dynamics in living systems and may facilitate investigations of SO2-associated signaling events in inflammatory pathological contexts.
Long S, Gao S, Liu Y, Zhang J, Shi H, Wang A, Zhang Y, Chen W, Zhou J
Endoscopy & Imaging (non-IUS) (4 papers)
Cellular therapies and immune reprogramming in inflammatory bowel disease: lessons learned and the promise of CAR T-cell therapy.★ Inflammatory bowel diseases | 2026-11-10
Despite major therapeutic advances, inflammatory bowel disease (IBD) remains incurable, and many patients experience primary non-response, secondary loss of response, progressive bowel damage, or lifelong dependence on immunomodulatory therapy. Cellular immunotherapies offer the possibility of moving beyond chronic immune suppression toward durable immune reprogramming. Earlier approaches in IBD, including hematopoietic stem cell transplantation, mesenchymal stem cells, and regulatory T-cell-based therapies, have provided important proof-of-concept but have been limited by toxicity, inconsistent efficacy, local rather than systemic effects, or unresolved manufacturing and durability challenges. Chimeric antigen receptor (CAR) T-cell therapy represents the next-generation strategy that combines potent immune remodeling with antigen-specific targeting. Initially developed for hematological malignancies, CAR T cells have recently shown striking efficacy in refractory autoimmune diseases, particularly through CD19-mediated depletion of B-lineage cells and induction of drug-free remission. In ulcerative colitis, renewed interest in B cells has been driven by evidence of plasmablast expansion, IgG-skewed humoral responses, anti-integrin αvβ6 autoantibodies, and the limitations of conventional anti-CD20 depletion. The first reported case of multidrug-resistant ulcerative colitis treated with CD19 CAR T cells demonstrated rapid clinical, biochemical, endoscopic, and histological remission, providing proof-of-concept for deep B-cell targeting in IBD. However, major uncertainties remain, including long-term durability, relapse after B-cell reconstitution, safety, cost, feasibility, and the risk of CAR T-associated gastrointestinal toxicity. Prospective trials with mechanistic mucosal monitoring are now needed to define the therapeutic potential and appropriate positioning of CAR-based strategies in IBD.
Parigi TL, Islam BN, Pizarro TT, Cominelli F
Colonoscopy-based Clostridioides difficile screening for inflammatory bowel disease patients.★ Gut microbes | 2026-11-08
Patients with IBD have an increased risk for Clostridioides difficile infection, and the significance of asymptomatic colonization is poorly understood. Overlapping symptoms often complicate diagnosis, and there is a lack of validated screening methods. Colonic wash aspirates collected during routine colonoscopies may offer a convenient screening option. We aimed to evaluate culture methods for detecting C. difficile colonization in IBD patients using colonic wash samples. Patients with Crohn’s disease or ulcerative colitis undergoing outpatient colonoscopy were enrolled. Clinical characteristics, IBD activity indices, and endoscopic scores were recorded. Colonic wash aspirates were centrifuged and cultured on selective CHROMID® media with and without broth enrichment. Isolates were confirmed by Gram stain and MALDI-TOF. PCR/qPCR identified tcdB gene carriage. Whole-genome sequencing was performed on selected isolates, and associations between clinical factors and colonization were assessed. Of the 121 patients enrolled, 10.7% (13/121) were colonized. Crohn’s patients were colonized more frequently than ulcerative colitis patients (13.3% CD, 8.2% UC). Among colonized patients, 53.8% (7/13) had C. difficile with detectable tcdB. Enrichment increased detection compared to direct plating. No clinical predictors of colonization were identified, but wash samples yielded sufficient DNA for sequencing with comparable depth to whole stool. Colonoscopy wash aspirates allow for the detection of asymptomatic C. difficile colonization in IBD. This screening method may provide a useful tool for investigating the prevalence, persistence, and clinical significance of C. difficile colonization in IBD and for informing future studies of CDI prevention.
Allegretti JR, Carlin A, McClure E, Delaney M, Bry L
Association of colonic motility on magnetic resonance enterography with endoscopic disease activity and chronic structural damage in ulcerative colitis.★ Inflammatory bowel diseases | 2026-11-04
Colonic motor dysfunction has been described in ulcerative colitis (UC) but has been less systematically assessed using quantitative imaging. We examined whether motility changes are associated with endoscopic disease activity and imaging features of disease chronicity. This prospective cross-sectional study included 49 adults with known UC who underwent magnetic resonance enterography and colonoscopy and 30 control participants. Colonic motility was quantified using GIQuant software. Endoscopic activity was graded by Mayo endoscopic subscore (MES) (0-3). Associations between motility and MES were assessed by ordinal regression and diagnostic performance by area under the curve. Imaging features of chronicity were recorded in segments with low endoscopic activity (MES ≤1). GIQuant values were lower in patients with UC than control subjects in every colonic segment (mean difference -205.9 to -110.1 units; all false discovery rate-adjusted P ≤.001). Higher motility was associated with lower MES (odds ratio per 1-SD increase, 0.38; 95% confidence interval, 0.28-0.52). The area under the curve was 0.83 for MES ≥1, 0.70 for MES ≥2, and 0.73 for MES ≥3. In segments with MES ≤1, chronicity features were associated with lower GIQuant values, with the largest differences observed for loss of haustration and increased pericolic fat. GIQuant-derived bowel wall motion is lower in UC and inversely associated with endoscopic activity. Correlations with chronic magnetic resonance enterography features remain present in segments with MES ≤1. Prospective validation with standardized colonic cine magnetic resonance imaging and concurrent symptom measures is needed before clinical use.
Sarikhani M, Menys A, Torabi A, Amouei M, Vahedi H, Sima AR, Naim I, Kolahdoozan S, Bhatnagar G, Colombel JF
Automated Clinical Decision Support and Electronic Health Record Tracking of Patients With Adenomas Found on Colonoscopy.★ JAMA network open | 2026-11-02
Surveillance colonoscopy following adenoma detection is essential for colorectal cancer prevention, yet systematic tracking within electronic health record (EHR) systems remains challenging, as they rely on manual data entry. To determine if implementation of an automatic tool in the EHR is associated with improved health care maintenance table updates for patients needing repeat colonoscopy for cancer screening after adenoma detection. This cohort study at a single tertiary care center within a large health care organization with EHR functionality included patients undergoing colonoscopy between November 2017 and December 2024. Eligible participants were adults aged 50 to 75 years undergoing colonoscopy for screening, surveillance, or diagnostic indications. Exclusion criteria included patients with inflammatory bowel disease, known colorectal cancer, or hereditary cancer syndromes. Data were analyzed between January and May 2025. A decision support tool was implemented that allowed gastroenterologists completing colonoscopies for patients with adenoma to choose follow-up intervals that would automatically populate the health maintenance tab. Rate of updates of the health maintenance table and percentage completion from gastroenterology vs primary care. A total of 35 802 patients met criteria (20 049 female [56.0%]; median [range] age: preintervention, 61 years [50-75 years]; postintervention, 62 years [50-75 years]); adenomas were detected in 8004 of 18 027 patients (44.4%) in the preintervention period and 8396 of 17 775 patients (47.2%) in the postintervention period. Health maintenance updates for patients with adenomas requiring closer surveillance increased significantly, from 83.4% (6672 of 8004 patients) to 94.2% (7913 of 8396 patients) following the intervention (P < .001). Gastroenterology team completion of health maintenance updates increased postintervention from 67.6% (5413 of 8004 patients) to 91.9% (7717 of 8396 patients). Conversely, primary care team updates decreased significantly from 9.3% (746 of 8004 patients) to 1.4% (118 of 8396 patients) following the intervention (P < .001 for both). Population health automatic updates occurred in a small number of patients in both periods. Implementation of automatic updates to the health maintenance section of the EHR was associated with significantly increased the reliability of postadenoma surveillance documentation; after the intervention, gastroenterology reporting increased while the primary care burden was reduced. These findings suggest that clinical decision support implementation is critical for accurate adenoma surveillance intervals.
O’Brien MT, Spann A, Zahn L, McCoy A, Horst SN
Extraintestinal Manifestations (4 papers)
Cutaneous presentations of digestive tract disorders and liver diseases.Review Dermatologie (Heidelberg, Germany) | 2026-11-10
A variety of skin conditions may be important diagnostic indicators for disorders of the digestive tract and liver. In inflammatory bowel diseases, the most common cutaneous manifestations are erythema nodosum and pyoderma gangrenosum. Similar to autoimmune liver diseases they are often associated with cutaneous manifestations such as hidradenitis suppurativa, vitiligo, psoriasis and alopecia areata. Lichen planus or porphyria cutanea tarda can also be induced by infectious hepatitis. Enteral malabsorption can lead to deficiencies and characteristic skin changes, such as celiac disease, acrodermatitis enteropathica, pellagra and scurvy. In addition, cutaneous sequelae, including various exanthems and adverse reactions, from drug treatment of intestinal and liver diseases are possible. Likewise, so-called paradoxical reactions in which new and previously absent skin conditions (e.g. psoriasis) may also develop, especially following treatment with biological products. Thus, gastroenterologists should recognize and diagnose cutaneous changes that are new or evolving in patients with intestinal and liver diseases in order to initiate appropriate therapy. Erkrankungen des Verdauungstrakts und der Leber können zu vielfältigen möglicherweise diagnostisch wegweisenden Hauterscheinungen führen. Bei entzündlichen Darmerkrankungen finden sich als häufigste Hautmanifestationen das Erythema nodosum und das Pyoderma gangraenosum. Wie auch bei autoimmunen Lebererkrankungen finden sich Assoziationen zu anderen entzündlichen Erkrankungen der Haut wie Hidradenitis suppurativa, Vitiligo, Psoriasis und Alopecia areata. Infektiöse Hepatitiden können einen Lichen planus (Knötchenflechte) oder eine Porphyria cutanea tarda an der Haut induzieren. Eine enterale Malabsorption kann zu Mangelzuständen und charakteristischen Hautveränderungen, wie der Zöliakie, Acrodermatitis enteropathica, Pellagra und Skorbut, führen. Daneben sind Folgen einer medikamentösen Behandlung von Darm- und Lebererkrankungen an der Haut wie vielfältige Exantheme und Unverträglichkeitsreaktionen möglich, aber auch sog. paradoxe Reaktionen, bei denen sich insbesondere unter Biologikatherapie unerwartet und vorher unbekannte Hauterkrankungen, wie z. B. eine Psoriasis, zeigen können. Daher sollten Gastroenterologen und Gastroenterologinnen neu auftretende oder sich wandelnde Hautveränderungen bei der Betreuung von Patienten mit Darm- und Lebererkrankungen erkennen und einordnen, um dann geeignete therapeutische Maßnahmen einleiten zu können.
Sticherling M
Primary Sclerosing Cholangitis in Inflammatory Bowel Disease: A 20-Year Cohort Study of Clinical Features and Transplant-Free Survival. Digestive diseases (Basel, Switzerland) | 2026-11-07
To evaluate prevalence, clinical characteristics, and long-term liver-related outcomes of primary sclerosing cholangitis (PSC) in patients with inflammatory bowel disease (IBD), focusing on determinants of transplant-free survival. In this retrospective cohort study, 2,376 patients with IBD were screened over 20 years, and 30 patients with PSC were identified. A matched IBD control group without PSC (n=90) was included for comparison. Clinical features, biochemical parameters, and liver-related outcomes were analyzed. Transplant-free survival was assessed using Kaplan-Meier analysis, and exploratory univariable Cox regression was performed to identify predictors of liver transplantation. PSC was identified in 1.3% of patients and was more frequently associated with ulcerative colitis. Large-duct PSC accounted for 87% of cases, and cirrhosis was present in 20% at diagnosis. During median follow-up of 60 months, liver transplantation occurred in 27% of patients. Baseline cirrhosis was strongly associated with reduced transplant-free survival (log-rank p=0.002) and increased risk of liver transplantation (HR 6.05, 95% CI 1.49-24.61). Median transplant-free survival was 4 years in cirrhotic patients, whereas it was not reached in non-cirrhotic patients. Biochemical response to ursodeoxycholic acid (UDCA) was not associated with transplantation or mortality. Compared with controls, PSC-IBD patients more frequently exhibited extensive colitis and backwash ileitis, while treatment exposure and remission rates were similar. PSC is a clinically relevant but uncommon comorbidity in IBD. Baseline cirrhosis emerged as the primary determinant of adverse liver-related outcomes, whereas biochemical response to UDCA was not prognostically informative. These findings suggest that disease stage at diagnosis, rather than biochemical response, should guide risk stratification and clinical decision-making in PSC.
Aliyev V, Bakkaloglu OK, Eskazan T, Kati O, Erzin YZ, Çelik AF, Hatemi AI
The gut-eye axis in inflammatory bowel disease: shared immune mechanisms and targeted therapies.Review Frontiers in immunology | 2026-10-26
Inflammatory bowel disease (IBD) is recognized not only as a disease confined to the intestinal tract, but also as a systemic immune-mediated disorder. Among its diverse extraintestinal manifestations, ocular complications, which range from self-limiting episcleritis to severe and sight-threatening uveitis and scleritis, represent a critical clinical challenge that profoundly impacts patient quality of life. This review synthesizes the epidemiological landscape and clinical spectrum of ocular manifestations in IBD, framing their pathogenesis through the emerging concept of the gut-eye axis. We critically examine the shared mechanistic pathways driving this bidirectional relationship, including the systemic dissemination of circulating inflammatory cytokines, aberrant lymphocyte homing, cross-reactive autoantibodies, shared genetic susceptibilities, and microbiota dysbiosis, which collectively compromise the blood-ocular barrier. Furthermore, we outline targeted therapeutic strategies, highlighting that while systemic anti-TNF agents remain the cornerstone for severe and refractory ocular inflammation, gut-selective biologics like vedolizumab necessitate careful application due to the risk of extraintestinal exacerbation. Finally, we underscore the indispensable role of multidisciplinary management and highlight future research trajectories.
Fu X, Hu S
Serial fecal calprotectin as a screening tool for subclinical ileitis in patients with idiopathic uveitis or scleritis: a prospective cohort study. Frontiers in medicine | 2026-10-26
Idiopathic uveitis accounts for 27%-51% of uveitis cases in Europe and the United States. Subclinical inflammatory bowel disease (IBD) may remain undiagnosed in patients with idiopathic uveitis or scleritis despite shared immunopathogenic mechanisms and the absence of digestive symptoms. Early identification may enable intervention within the inflammatory window of opportunity, yet subclinical ileitis has not been systematically explored in this population. We evaluated the diagnostic performance of serial fecal calprotectin for identifying subclinical inflammatory bowel disease in a prospective cohort of 69 patients with idiopathic uveitis or scleritis, using a baseline measurement repeated at 6-12 months if negative or at three months if positive, defining four longitudinal patterns (A-D). Subclinical ileitis was confirmed by capsule endoscopy and/or colonoscopy in 5 of the 62 patients with an evaluable outcome (8.1%). Baseline fecal calprotectin was significantly higher in patients with confirmed ileitis (p = 0.024), a difference that became more pronounced at the second determination (p = 0.002). The pattern of persistent elevation (subgroup D) showed the best diagnostic balance: sensitivity 100% (exact 95% CI: 47.8-100.0), specificity 82.5% (95% CI: 70.1-91.3), negative predictive value 100% (95% CI: 92.5-100.0), and positive likelihood ratio 5.7 (95% CI: 3.25-10.01). ROC curve analysis showed a numerically higher discriminative capacity for the second calprotectin determination (AUC: 0.932; 95% CI: 0.850-1.000) than for the baseline measurement (AUC: 0.809; 95% CI: 0.652-0.966), although a formal DeLong comparison between both c-statistics found no statistically significant difference (p = 0.242). This exploratory, hypothesis-generating cohort suggests that a persistently elevated fecal calprotectin trajectory identifies a subgroup of patients with idiopathic uveitis or scleritis who may warrant digestive evaluation; because subgroups A and C were not endoscopically verified, the reported sensitivity and negative predictive value are estimates conditioned on this verification scheme and on only five events, not validated evidence that a negative trajectory excludes subclinical ileitis. Confirmation in larger, prospectively verified, multicenter cohorts is required before any screening recommendation can be made.
Lavilla Olleros C, Menchén L, Ramos-Ferreira J, Merino Rodríguez B, de Miguel-Yanes JM, Gutierrez Bonet R, Torresano Rodríguez J, Ausín García C, Puertas López C, Alvarez-Sala Walther L
Genetics & Genomics (4 papers)
Bidirectional association and mechanisms between periodontitis and inflammatory bowel disease: A systematic review. International immunopharmacology | 2026-11-06
Periodontitis and inflammatory bowel disease are bidirectionally associated, yet the molecular mechanisms linking the two mucosal sites have not been systematically integrated. This systematic review synthesized these bidirectional pathways and identified core immunological hubs, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Mechanistic studies formed the core evidence, supplemented by population-based epidemiological and Mendelian Randomization studies; evidence strength was graded using a prespecified scoring system with a sensitivity analysis. Thirty-nine studies were included. Most mechanistic evidence derived from dextran sulfate sodium-induced (ulcerative colitis-like) colitis models, whereas validation in Crohn’s disease-relevant models was limited. In the forward direction (periodontitis to inflammatory bowel disease), mechanisms comprised microbial translocation, metabolic disturbance, immune cell gut homing, and intestinal barrier disruption. The reverse direction was supported exclusively by preclinical models and is presented as a hypothesis. T helper 17 and regulatory T cell imbalance and dysregulated macrophage polarization constituted two shared hubs, interconnected via interleukin-1 beta and interleukin-17 A crosstalk. Macrophage polarization was the only hub with evidence in both directions, whereas Th17/Treg imbalance was robust only in the forward direction; however, a quality-restricted sensitivity analysis downgraded macrophage polarization to insufficiently supported. Preclinical modulation of either hub concurrently improved colitis and periodontitis, but clinical efficacy remains unestablished. These findings support a bidirectional association with mechanistic plausibility, although definitive causality is unproven. An asymmetrical dual-hub model is proposed for oral-gut axis research, predominantly in ulcerative colitis-like models; extrapolation to Crohn’s disease requires independent validation.
Shen D, Lv Y, Wu W
Combined radiofrequency electromagnetic and pulsed magnetic field exposure attenuates histological and molecular markers of acute colonic injury in young rats. Electromagnetic biology and medicine | 2026-11-04
Inflammatory bowel disease involves epithelial injury, ulceration, apoptosis, inflammation, and oxidative-stress dysregulation. Although bioelectromagnetic fields may modulate tissue responses, their effects on acute colitis remain unclear. This exploratory study assessed histological and molecular changes associated with combined radiofrequency electromagnetic field (RF-EMF) and pulsed magnetic field (PMF) exposure in acetic-acid-induced colitis.Thirty-two young female Wistar albino rats were allocated to Control, Colitis, Colitis+RF-EMF+PMF, or RF-EMF+PMF groups (n=8 each). Colitis was induced intrarectally with 4% acetic acid. Exposure comprised RF-EMF (27.12 MHz, 30 min/session, 12 cycles/day) and PMF (0.5 mT, continuous). After seven days, distal colonic specimens underwent semiquantitative histopathology, crypt morphometry, immunohistochemistry for CAS-3, IL-6, and TNF-α, and RT-qPCR for SIRT-1, NRF-2, and HO-1. Colitis caused histological injury, reduced crypt dimensions, increased CAS-3, IL-6, and TNF-α immunopositivity, and decreased SIRT-1, NRF-2, and HO-1 expression. Compared with untreated colitis, combined exposure increased crypt depth and width and reduced all three immunohistochemical markers (all Tukey-adjusted p<0.001). Overall histopathological injury was lower but not statistically significant (Dunn-adjusted p=0.068), whereas submucosal inflammatory infiltration decreased significantly (p=0.048). NRF-2 expression increased (Tukey-adjusted p=0.002); SIRT-1 and HO-1 increased numerically without statistical significance (p=0.057 and 0.134).Combined RF-EMF+PMF exposure was associated with preserved crypt architecture, reduced apoptotic and inflammatory immunopositivity, and increased NRF-2 expression. Absent barrier-function testing and incomplete RF dosimetry preclude conclusions regarding restored epithelial barrier function or established therapeutic efficacy. Inflammatory bowel disease damages the lining of the intestine, leading to inflammation, tissue injury, and disruption of the normal intestinal structure. Although medications are available, some patients do not respond adequately or experience side effects. Therefore, researchers are investigating new non-drug approaches that may help protect intestinal tissue and support healing.In this study, we examined whether exposure to two types of electromagnetic stimulation (radiofrequency electromagnetic fields and pulsed magnetic fields) could reduce intestinal damage in an experimental model of colitis. Colitis was induced in young rats using acetic acid, which produces inflammation and injury in the colon. Some animals received electromagnetic field treatment for seven days, while others did not.Rats that received the combined electromagnetic therapy showed significantly less intestinal damage. Microscopic examination demonstrated better preservation of the intestinal lining and reduced inflammatory cell infiltration. In addition, markers related to inflammation and cell death were lower, while protective cellular pathways involved in antioxidant defense were improved.Importantly, healthy rats exposed to the same electromagnetic fields did not show signs of tissue injury or inflammation. These findings suggest that controlled electromagnetic field exposure may help reduce intestinal inflammation and support tissue repair. Further studies are needed to determine whether this approach could eventually contribute to new supportive treatment strategies for inflammatory bowel disease.
Elmas A, Asci H, Tepebası MY, Taner R, Selver MB, Comlekci S, Akcam M, Ozmen O
From Mechanism to Management: The Link Between Inflammatory Bowel Disease and Cardiovascular Disease.Review Immunity, inflammation and disease | 2026-11
Inflammatory bowel diseases (IBDs) constituting the ulcerative colitis (UC) and Crohn’s disease (CD) primarily affect the gastrointestinal tract and have been associated with the development of cardiovascular disease (CVDs). To strengthen this further, the focus of our narrative review is to highlight the clinical significance of understanding this association. We conducted a narrative review to discuss the mechanisms of pathogenesis underlying the link between the management of inflammatory bowel disease and cardiovascular disease. The pathogenesis of the link likely involves dysregulated immune responses leading to overactivation of pro-inflammatory cytokines, suggesting a shared inflammatory pathway. Both diseases share common risk factors such as obesity, diabetes, and gender. Genetic factors, including mutations in NOD2 and CDKN2A, also play a role in the overlap between IBDs and CVDs. Despite the recent developments, conventional cardiovascular risk assessment tools may not fully capture the potential elevated cardiovascular threat in IBD patients. Thus, proactive investigation with advanced diagnostic tools such as coronary artery calcium (CAC) scoring is crucial in reducing cardiovascular morbidity and mortality in these patients. Nevertheless, future research is needed to further clarify disease activity and its correlations. NA.
Yasmin F, Ahmed M, Bin Iftikhar T, Rab AU, Qazi MS, Asghar MS, Eljack MMF, Pandya K, Alraies MC
Glucomannan From Acrocomia corumbaensis (Bocaiuva) Attenuates Pain and Inflammation in DSS-Induced Colitis via Mucus Barrier Protection. Clinical and experimental pharmacology & physiology | 2026-11
Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by weight loss, abdominal pain, diarrhoea and rectal bleeding. Polysaccharides have recognized protective and immunoregulatory effects in the gut. This study investigated BFS, a glucomannan extracted from bocaiuva, in dextran sulphate sodium (DSS)-induced colitis. Male and female C57BL/6J mice received 3% DSS and BFS (1, 10, or 100 mg/kg, orally) for 7 days. Disease activity index (DAI) was monitored daily, while abdominal mechanical hypersensitivity and behavioural tests were assessed using von Frey filaments, elevated plus maze and nest-building tests. Colons were collected for histological and biochemical analyses. BFS did not prevent DAI increase, but at 100 mg/kg reduced mechanical hypersensitivity. BFS prevented histopathological damage, inflammatory infiltration and alterations in mucosal architecture. BFS also reduced MPO, IL-1β, TNF-α, IFN-γ and NFκB phosphorylation. Additionally, BFS preserved mucin content and MUC-2 expression, with QCM-D analysis corroborating its mucoadhesive potential. In males, BFS improved behavioural welfare parameters. Although BFS did not improve clinical signs, it preserved the mucus barrier and exerted anti-inflammatory and analgesic effects, supporting its therapeutic potential in UC.
Brito MSC, Taporosky AK, Rech KS, Santos LBS, Gois MB, de Souza LFN, de Freitas RA, Azevedo CAB, Mathias C, Cordeiro LMC
Nutrition & Lifestyle (4 papers)
Epstein-Barr virus and inflammatory bowel disease: a systematic review of its clinical significance and potential pathogenic role.★ Inflammatory bowel diseases | 2026-11-10
Several studies report an association between Epstein-Barr virus (EBV) and inflammatory bowel disease (IBD). This review critically synthesizes current evidence on these association between EBV and IBD, its potential mechanisms, clinical implications, and research gaps. A systematic search identified studies investigating EBV in IBD using serological, molecular, and tissue-based approaches. Data on EBV prevalence, viral load, disease phenotype, treatment status, and clinical outcomes were extracted, and study quality was assessed. A narrative review examined proposed mechanisms that may potentially link EBV to intestinal inflammation. From 7271 citations, 45 studies met inclusion criteria. EBV was more frequently detected in intestinal tissue from IBD patients than in controls, particularly in active or refractory disease, whereas findings for seroprevalence and blood-based markers were less consistent. Some longitudinal studies reported associations between prior EBV exposure and subsequent IBD, particularly Crohn’s disease, but these observations do not establish a causal relationship. Proposed mechanisms involving EBV-infected B cells, molecular mimicry, and altered cytokine signaling provide biological plausibility but remain unproven in IBD. EBV latency programs and age at seroconversion may influence disease progression and reactivation risk, although data remain limited. Corticosteroids and therapy with infliximab plus azathioprine have been associated with higher EBV loads, especially in refractory disease, yet these findings may be confounded by disease severity and treatment exposure. Current evidence supports an association between EBV and IBD, particularly in severe and refractory disease but does not establish-and equally does not exclude-a pathogenic role for EBV. Considerable methodological heterogeneity in study design and EBV detection methods and the observational nature of the available data limit causal interpretation. Prospective mechanistic studies are needed to determine whether EBV is a causal contributor, a disease modifier, or a marker of underlying immune dysregulation.
Estevinho MM, Said H, Nandy A, Snapper SB, Colombel JF, Agrawal M
An ulcerative colitis taxonomy defined by individual patient-reported response trajectories.★ Nature medicine | 2026-11-09
A barrier to precision medicine for ulcerative colitis (UC) is the inability to predict and mechanistically explain treatment responses. Using patient-reported outcomes (PROs) from a phase 3b comparative trial of 768 participants, we identified four distinct patient response-trajectory groups for vedolizumab (anti-integrin) and adalimumab (antitumor necrosis factor). Validation in a second phase 3 trial of 576 participants linked PRO-defined vedolizumab trajectories to long-term disease complications. Bulk, single cell, and spatial transcriptomics and proteomics identified vascular inflammation as associated with vedolizumab nonresponse through interactions between SPP1+ macrophages and endothelial cells. In two separate real-world cohorts of 4,981 and 3,854 patients with UC, concomitant use of renin-angiotensin system inhibitors (modulators of vascular inflammation) was associated with reduced long-term complications for vedolizumab but not anticytokine therapies. These findings define a response-trajectory-based taxonomy that requires prospective validation for clinical utility and applications for selecting vedolizumab combination therapy in UC.
Schreiber S, Yajnik V, Wei C, Paraskevopoulou MD, Farahmand S, Cheng J, Simpson K, Lin Z, Agboton C, Panchal P
Allobaculum stercoricanis and Its Postbiotics Alleviate Dextran Sulfate Sodium (DSS)-Induced Colitis through the Regulation of theTLR4/NF-κB Signaling Pathway. Journal of agricultural and food chemistry | 2026-11
Inflammatory bowel disease (IBD) is a chronic intestinal disorder that has become a global public health concern. Postbiotics offer advantages in biosafety and reproducibility over probiotics. Here, we demonstrated that live Allobaculum stercoricanis (A. stercoricanis) and its two postbiotic preparations─inactivated bacterial cells (POST) and cell-free fermentation supernatant (CFS)─effectively alleviated dextran sulfate sodium (DSS)-induced colitis in mice. Integrated gut microbiome and serum metabolomics analyses indicated that these interventions may act through modulating bile acid metabolism and Toll-like receptor signaling pathways. Further investigations combining postbiotic metabolomics, network pharmacology, molecular docking, and molecular dynamics simulations identified α-muricholic acid (α-MCA) as a candidate functional metabolite, with the farnesoid X receptor (FXR) as a potential target. We hypothesize that α-MCA may contribute to ameliorating intestinal inflammation through engagement of FXR and suppression of the TLR4/NF-κB signaling pathway. These findings provide new insights into postbiotic-based therapeutic strategies for IBD.
Wang T, Wang J, Huangfu B, He X, Huang K
Use of a novel low-fat hydrolyzed diet in the management of dogs with chronic enteropathy. Journal of veterinary internal medicine | 2026-11
Dietary management plays a central role in the diagnosis and treatment of chronic enteropathy (CE) in dogs. Although hydrolyzed-protein diets are commonly used in patients with CE, and dietary fat restriction is recommended in selected gastrointestinal disorders, the combined effect of low fat and hydrolyzed protein has not been specifically evaluated. Assess clinical response and acceptability of a low-fat, hydrolyzed diet in dogs with CE. Thirty-one client-owned dogs. Prospective clinical study. Dogs were fed a commercial low-fat (2.01 g/100 kcal metabolizable energy) hydrolyzed salmon protein diet and stratified according to previous dietary history. Dogs were evaluated at baseline, 1 month, and 3 months. The primary outcome was clinical response, classified as complete response (CR), partial response (PR), or non-response (NR) based on gastrointestinal signs and the Canine Inflammatory Bowel Disease Activity Index (CIBDAI) score. Dogs with CR or PR were considered responders. Diet acceptability was assessed. At T1, 20 of 31 (64.5%) dogs were categorized as CR, 3 of 31 (9.7%) as PR, and 8 of 31 (25.8%) as NR. Twenty-three of 31 (74.2%) dogs had a positive clinical response. The CIBDAI scores decreased significantly from T0 to T1 (P < .001). At T2, 94.4% of initial responders maintained CR. Diet acceptability was excellent in 75.0% of cases. This low-fat, hydrolyzed diet had significant short- and mid-term effectiveness and was well tolerated in dogs with CE, reinforcing its potential as a treatment for food-responsive enteropathy.
Hernández-Anllo C, Feo L, Hervera M, Puig J
Quality of Life & PROs (4 papers)
Beyond the gut: neuroinflammation as a driver of anxiety and depression in inflammatory bowel disease.Review The Biochemical journal | 2026-12
Anxiety and depression frequently co-occur with inflammatory bowel disease (IBD), with prevalence rates substantially higher than in the general population. Emerging evidence further indicates that active IBD is associated with more severe psychological symptoms, while anxiety and depression can worsen intestinal inflammation, highlighting a bidirectional relationship. Chronic intestinal inflammation is increasingly recognized as a driver of neuroinflammation, a key mechanism underlying mood disorders. In IBD, disruption of the intestinal epithelial barrier permits metabolites and enteric signaling molecules to enter the circulation, triggering systemic inflammation and crossing the more permeable blood-brain barrier (BBB) to promote neuroinflammation. Other relevant components of the gut-brain axis contributing to IBD-associated neuroinflammation include the enteric nervous system, vagus nerve (VN), hypothalamic-pituitary-adrenal (HPA) axis, and tryptophan-kynurenine metabolism. Within the brain, neuroinflammation characterized by glial activation, inflammatory mediator release, and oxidative stress disrupts neurogenesis and synaptic plasticity in regions such as the hippocampus and prefrontal cortex, contributing to anxiety and depression. Conversely, anxiety and depression can amplify systemic inflammation through dysregulation of the VN and HPA axis, thereby exacerbating IBD. This reciprocal interaction adversely affects disease severity, quality of life, and therapeutic outcomes, underscoring the need to better define its underlying mechanisms. The present review synthesizes current clinical, translational, and experimental evidence on the bidirectional crosstalk between IBD and mood disorders. We also highlight key knowledge gaps, future research directions to identify the cellular and molecular mediators of this interaction, and emerging therapeutic strategies for the integrated management of both conditions.
Bielamowicz D, Schoonover B, Sodhi K, Borthakur A
Amuc_1100 suppresses T cell viability and CXCL12‑induced T cell migration through GLI2 upregulation. Tissue & cell | 2026-11-05
Maintaining intestinal homeostasis requires precise regulation of intestinal T cell trafficking. Dysregulated T cell activity is a key driver of chronic inflammation, as seen in inflammatory bowel disease. The gut commensal Akkermansia muciniphila and its membrane-associated protein Amuc_1100 exhibit anti‑inflammatory effects and are negatively correlated with disease severity. However, their direct mechanistic impact on T cell activity remains undefined. This study reveals that Amuc_1100 modulates human T cell function by activating TLR2, which upregulates the transcription factor GLI2. Mechanistically, GLI2 upregulation leads to downregulation of CD25 and CXCR4, ultimately suppressing T cell viability and CXCL12-induced T cell migration. To comprehensively characterize the impact of Amuc_1100 on T cell migration, we employed a D⁴-Chip featuring four parallel units for high‑throughput, real‑time analysis. Its confined cell-isolation structure positions individual T cells under tissue‑like physical constraints, enabling observation of their migration within a stable CXCL12 gradient and providing a physiologically relevant model for quantifying single‑cell migratory behavior. D⁴-Chip analysis demonstrated that Amuc_1100 broadly impairs T cell migration, as evidenced by significant reductions in the number of migrating cells, their average displacement towards gradient, average accumulated migration distance, and average migration velocity, coupled with an increased frequency of migration pauses compared to the control. GLI2 inhibition reversed these effects, confirming that Amuc_1100 modulates GLI2 to suppress T cell migration. Collectively, this work identifies GLI2 as a novel therapeutic target for modulating T cell homing in intestinal inflammation and establishes a microfluidic platform for discovering potential drugs targeting dysregulated T cell responses.
Ren X, Liu Y, Du Y, Yang J, Yang X, Lin F, Yang K, Ye S
Work disability in patients with newly diagnosed inflammatory bowel disease: Results from the population-based IBSEN III cohort.★ Inflammatory bowel diseases | 2026-11-04
This study aimed to compare the proportion of Crohn’s disease (CD) and ulcerative colitis (UC) patients receiving work disability (WD) benefits with the corresponding proportion in the background population at diagnosis and after 1 year, and to assess associations between selected variables and WD. Adults from a population-based inception cohort with WD data at diagnosis and/or 1-year follow-up were included. WD was defined as receiving work assessment allowance (AAP) or disability pension (DP). Relative risks (RRs) for AAP and DP were calculated vs. national registry proportions stratified by age and sex, overall RRs were age standardized. Multivariable logistic regression assessed associations between WD and selected variables. At diagnosis, risk of AAP was increased for UC (RR, 1.5; 95% confidence interval [CI], 1.1-2.1) and CD patients between 30-39 years old (RR, 2.8; 95% CI, 1.1-5.8). AAP risk was increased at 1-year for both UC (RR, 1.6; 95% CI, 1.1-2.4) and CD (RR, 3.6; 95% CI, 2.4-5.2). DP risk was comparable with the background population. Higher general self-efficacy and health-related quality of life were associated with lower odds of WD, whereas disease-activity variables were not. Older age, comorbidities, and lower education were also associated with increased odds of WD in UC. After 1 year, patients with UC and CD had increased risk of AAP. Lower general self-efficacy and poorer health-related quality of life were associated with higher WD, suggesting a potential window for targeted interventions to reduce AAP and prevent or delay DP.
Lund C, Hagen M, Strande V, Bengtson MB, Aabrekk TB, Boyar R, Frigstad SO, Aass Holten KI, Hovde Ø, Huppertz-Hauss G
Phthalates exposure and gastrointestinal health: a comprehensive review of toxic mechanisms and emerging mitigation strategies.Review Current research in toxicology | 2026-10-24
Phthalates are widely used plasticizers that can leach into food products, making dietary exposure a significant food safety concern. Increasing evidence indicates that phthalates adversely affect gastrointestinal health and contribute to the development of inflammatory bowel disease (IBD), metabolic disorders, diabetes, and cardiovascular disease. Mechanistic studies demonstrate that phthalates disrupt gut microbiota composition, diversity, and metabolic activity, compromising microbial barrier function integrity and facilitating pathogen translocation. They also impair intestinal barrier function by reducing mucus secretion, altering tight junction proteins, and increasing epithelial permeability. Furthermore, phthalates promote intestinal inflammation by enhancing pro-inflammatory cytokine production, suppressing anti-inflammatory responses, and disrupting immune cell homeostasis. Emerging findings reveal detrimental effects on enteroendocrine and enteric glial cells, resulting in altered hormone secretion, impaired gut-brain signaling, and disrupted intestinal motility. This review summarizes current evidence on molecular mechanisms underlying phthalate-induced gastrointestinal toxicity and highlights potential mitigation strategies, including polyphenols, flavonoids, probiotics, prebiotics, and pharmacological interventions.
Anwar C, Perumal PK, Hsu PC, Lai CS
Drug Safety & Pharmacovigilance (3 papers)
Effectiveness and Safety of Janus Kinase Inhibitors in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis of Real-world Studies. Digestion | 2026-11-07
Janus kinase (JAK) inhibitors (JAKis) are increasingly used to treat inflammatory bowel disease (IBD), but most pivotal data come from randomized controlled trials. Real-world evidence is needed to clarify their effectiveness and safety in routine clinical practice. We conducted a systematic review and meta-analysis of real-world studies reporting outcomes in IBD patients treated with JAKis (tofacitinib, upadacitinib, or filgotinib). PubMed, Embase, Web of Science, and the Cochrane Library were searched from inception to August 11, 2025. Primary outcomes were clinical response and clinical remission; secondary outcomes included steroid-free clinical remission, endoscopic and biochemical responses, and safety outcomes. 63 studies involving 8130 IBD patients were included. In ulcerative colitis (UC), pooled clinical response and remission rates were 55% and 43% for tofacitinib, 77% and 65% for upadacitinib, and 69% and 55% for filgotinib; steroid-free remission with tofacitinib approached 50% at 1 year. In Crohn’s disease (CD), upadacitinib achieved clinical response and remission in around two thirds of patients. Across agents, safety profiles were acceptable: mortality was 0%; hospitalization and treatment discontinuation rates were 8% and 28% for tofacitinib, 5% and 12% for upadacitinib, and 4% and 15% for filgotinib; serious adverse events occurred in ≤8% of patients. Descriptive real-world data show that tofacitinib, upadacitinib, and filgotinib all provide clinically meaningful effectiveness in UC and CD, complementing evidence from randomized trials. Across real-world cohorts, JAKis have generally acceptable safety profiles, with low rates of serious adverse events and no observed drug-related mortality.
Huang J, Wu Y, Zhang C, Jin X, Yang S, Lan X, Zeng P, Lin G, Lu H
Efficacy and safety profile of advanced therapies in Crohn’s disease: a systematic review and network meta-analysis. Pharmacological reports : PR | 2026-11-04
Crohn’s disease (CD) is a chronic inflammatory bowel disorder characterized by a relapsing-remitting course and substantial heterogeneity in clinical presentation. This study aimed to assess the comparative efficacy and safety of approved biologic and small-molecule therapies for CD, with particular emphasis on guselkumab and mirikizumab. A systematic review and frequentist network meta-analysis (NMA) was conducted in accordance with PRISMA-NMA, the Cochrane Handbook, and ISPOR guidelines. MEDLINE, EMBASE, and the Cochrane Library were searched from inception to June 2026. Phase 3 randomized controlled trials (RCTs) evaluating adalimumab, guselkumab, infliximab, mirikizumab, risankizumab, vedolizumab, upadacitinib, or ustekinumab in adults with CD were included. A total of 27 RCTs were included. During induction therapy, guselkumab 400 mg achieved the highest P-scores for both clinical response and remission and was associated with higher odds of these outcomes compared with placebo and several active comparators. Mirikizumab was also more effective than placebo but ranked in the middle of the treatment hierarchy. During maintenance therapy, guselkumab 200 mg and 100 mg achieved the highest rankings for clinical response and remission; however, differences between guselkumab and several active comparators were not statistically significant. These comparisons were predominantly informed by indirect evidence and should not be interpreted as establishing definitive clinical superiority. No consistent evidence of major safety differences was observed across interventions; however, heterogeneity and inconsistency in several safety networks limited the certainty of the comparisons. Although guselkumab achieved favourable rankings for serious adverse events and serious infections, few statistically significant differences were observed between active treatments. The results should be interpreted in the context of indirect comparisons and methodological heterogeneity among included studies. Within the limitations of an NMA based predominantly on indirect evidence, guselkumab achieved the highest rankings for several efficacy outcomes during both induction and maintenance therapy. Mirikizumab showed higher odds of response and remission than placebo, although its node was informed by a single eligible phase 3 study. Given differences in study populations and trial designs, particularly in maintenance studies, these findings should be interpreted cautiously and not as evidence of definitive clinical superiority.
Kasprowicz K, Moćko P, Śladowska K, Holko P, Kawalec P
Combination advanced therapy use and infection risks in immune-mediated inflammatory diseases. Rheumatology (Oxford, England) | 2026-11-03
To evaluate real-world evidence on combination advanced therapy (CAT) exposures and safety in patients with immune-mediated inflammatory diseases (IMIDs). We conducted a retrospective new-user cohort study of individuals initiating advanced therapies between 2016 to 2023 using MarketScan® databases. We assessed for overlapping (≥30 days) exposures to different targeted synthetic or biologic disease-modifying antirheumatic drug (ts/bDMARD) classes (CAT episodes). We described baseline characteristics and calculated multivariate hazard ratios (HRs) for first CAT episode persistence. We estimated HRs for first serious infection (i.e. requiring hospitalization or intravenous antibiotics) comparing combined versus single advanced therapy, stratified by CAT regimens and IMIDs. A total of 270,198 individuals initiated 693,375 advanced therapy episodes, including 38,456 (14.2%) who started 52,212 CAT episodes. The most common IMIDs among CAT users were psoriasis, inflammatory bowel disease, rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis (AxSpA). Among CAT episodes, 51.2% involved TNFi exposure. Median duration of first CAT exposure was 42 days. CAT was associated with 5.2 serious infections per 100 person-years, yielding a HR of 1.61 (95% CI: 1.46-1.78) compared to monotherapy. Anti-adhesion agents combined with TNFi was associated with serious infection (HR 1.49, 95% CI 1.09-2.04) compared to other combinations. In IMID-stratified analysis, CAT (versus monotherapy) was associated with higher risk of serious infection across all diseases, except AxSpA. CAT was predominantly used within the spondyloarthritis umbrella of diseases. CAT exposure was associated with short duration and increased serious infection risk, although this risk varied by CAT regimen and underlying IMID.
Kwok TSH, Widdifield J, Moura CS, Bernatsky S, Curtis JR, Chandran V, Kaplan GG, Rahman P, Poddubnyy D
IBD-associated Neoplasia (3 papers)
Mucosal abnormalities as key predictive factors of colorectal cancer in ulcerative colitis.★ Endoscopy | 2026-11-09
Although an increased risk of colorectal cancer (CRC) among patients with ulcerative colitis (UC) is well established, the magnitude and determinants of excess risk remain ambiguous. This uncertainty hampers risk stratification and evidence-based endoscopic surveillance. We empaneled a population-based cohort of incident UC cases in Scandinavia, achieved a median follow-up of 15.0 years through record linkages, designed a case-cohort study, and undertook standardized data abstraction from hospital records of 566 patients with CRC and 720 patients from a sub-cohort randomly sampled at baseline. We fitted weighted multivariable Cox proportional hazard models to estimate hazard ratios (HRs) with 95%CIs, which approximates analyzing the full cohort of 90 780 subjects. We confirmed 2-fold higher CRC risk in patients with pancolitis compared with proctitis (HR 2.3, 95%CI 1.5-3.4). We saw no association between severe macroscopic (HR 1.1, 95%CI 0.7-1.8) or microscopic (HR 1.5, 95%CI 1.0-2.3) inflammation and CRC risk. In contrast, low grade dysplasia predicted a more than 3-fold, and adenomas an almost 10-fold excess rate of CRC (HR 9.8, 95%CI 5.2-18.6). Overall, HRs did not depend on follow-up time (0-1 years, 1-8 years, and >8 years). Pharmacologic treatments with biologic drugs (HR 2.4, 95%CI 0.7-7.7) or immunomodulators (HR 1.1, 95%CI 0.7-1.7) did not significantly reduce the CRC rate. In patients with UC, mucosal abnormalities rather than disease extent and inflammation were the strongest predictive factors of CRC. Our findings do not support prevailing recommendations for endoscopic surveillance.
Högdén A, Perrin V, Adami HO, Jess T, Larsen L, Hvidbjerg Gantzel R, Ye W, Eloranta S, Grimstad T, Helsingen LM
Small neuroendocrine proliferations in columnar mucosa at or near the gastroesophageal junction: a finding potentially related to proton pump inhibitor use and/or gastroesophageal reflux disease. Histopathology | 2026-11-03
Neuroendocrine proliferations have been described in gastrointestinal (GI) mucosa associated with chemoradiation and inflammatory bowel disease (IBD) and can also be seen in gastric mucosa in hypergastrinemic conditions. We have encountered small clusters of neuroendocrine cells in the lamina propria, designated herein as neuroendocrine micronodules (NMs), in biopsies taken at and around the gastroesophageal junction (GEJ) in patients without histories of chemoradiation, IBD or autoimmune metaplastic atrophic gastritis (AMAG) and sought to further characterize their clinicopathological features. Nine patients with NMs were identified during routine signout. An additional 66 consecutive patients with GEJ biopsies containing ≥1 fragment of columnar mucosa were prospectively evaluated. NMs were identified on haematoxylin and eosin staining and confirmed with chromogranin A immunohistochemistry. NMs were identified in 8% (5/66) of GEJ biopsies in the prospective cohort. Of the 14 total patients with NMs, the median age was 51 years (range 25-78 years) with slight male predominance (1.7:1). 79% reported proton pump inhibitor (PPI) use, 71% had gastroesophageal reflux disease (GERD) and 36% had hiatal hernia. None had IBD, chemoradiation or prior neuroendocrine neoplasia. Associated histological findings included pancreatic metaplasia in 57%, intestinal metaplasia in 7% and linear neuroendocrine cell hyperplasia in 64%. Twelve patients had concurrently sampled oxyntic mucosa and all lacked evidence of AMAG. NMs at the GEJ can be found in up to 8% of unselected biopsies and may occur in patients without AMAG. Possible aetiologies include PPI-associated ECL hyperplasia and/or GERD-mediated injury; however, definitive characterization requires further studies.
McCloskey A, Waters KM, Kozak M, Guindi M, Lai KK, Larson BK, Hutchings DA
Crosstalk between IL-6/JAK/STAT3 and TNF-α/NF-κB signaling in colitis-associated colorectal cancer: epigenetic reprogramming, evidence boundaries, and opportunities for disease management.Review Frontiers in immunology | 2026-10-26
Colitis-associated colorectal cancer (CAC) arises through the interaction of chronic mucosal inflammation, genetic evolution and durable changes in gene regulation. Among the inflammatory networks implicated in experimental and human studies, interleukin-6 (IL-6)/Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) and tumor necrosis factor-alpha (TNF-α)/nuclear factor-kappaB (NF-κB) provide mechanistically informative routes by which cytokine exposure can influence DNA methylation, chromatin regulation and non-coding RNA programs. The best-supported examples include IL-6-associated DNMT1 activity and SOCS3 promoter hypermethylation, NF-κB p65/DNMT3A-associated miR-148a methylation, and STAT3-dependent miR-214 induction. These circuits should be regarded as representative mechanisms supported in specific model systems rather than universal initiating pathways in all human CAC lesions. Recent work further demonstrates that colonic stem cells can retain chromatin accessibility changes after experimental colitis resolves, providing direct evidence for durable inflammatory epigenetic memory. This review therefore separates evidence from human CAC or dysplasia, non-neoplastic inflammatory bowel disease (IBD) mucosa, inflammation-driven animal models, sporadic colorectal cancer (CRC) and cell-line systems. We integrate cytokine-linked epigenetic mechanisms with genetic and clonal evolution, define field cancerization operationally, and distinguish persistent epigenetic memory from transient inflammatory transcription. The translational sections are framed as an outlook: no epigenetic biomarker or epigenetic drug is currently established for CAC surveillance or prevention. We summarize the validation requirements for tissue, blood and stool biomarkers; classify therapeutic concepts by evidence level; and propose a patient-level roadmap for single-cell and spatial studies. The resulting framework emphasizes evidence-graded mechanisms and prospective validation rather than assuming that biologically plausible signals are clinically actionable.
Yuan J, Liao J, Li F, Xie D, Zuo Z, Zhang D, Zhang T
Guidelines & Consensus (2 papers)
Correction: Time to rethink washout periods in inflammatory bowel disease clinical trials: an international Delphi consensus.★ Journal of Crohn’s & colitis | 2026-11
The Human Gut Cell Atlas v1.0: A Unified, Community-Built Reference of Cellular Diversity Across the Gut. bioRxiv : the preprint server for biology | 2026-10-23
Single-cell RNA-sequencing (scRNA-seq) studies have transformed our understanding of cellular diversity in the human intestine, but differences in anatomical sampling, experimental processing and cell-type nomenclature limit comparison across datasets. Here, we present the Human Gut Cell Atlas (HGCA) V1, a community-curated reference of 944,390 healthy and disease-adjacent intestinal cells from 502 samples, 265 donors and 24 landmark studies, linked to detailed anatomical, clinical, and technical metadata. As this metadata is of critical importance to human biology, we developed MetaManager, an open source data management framework for standardized metadata collection and tracking. A five-level consensus taxonomy resolves 94 homeostatic cell identities and enables transferrable, high-resolution annotation of new gut datasets. By assembling cell identity, sampling metadata, and independent spatial validation, intestinal segment and radial tissue depth were revealed to systematically shape cellular composition and transcriptional state, enabling inference of the presence of sampling-dependent tissue niches, including lymphoid follicles. Reference mapping accurately and rapidly recovered cohort-level Crohn’s disease and treatment signatures without de novo annotation, while mapping human intestinal organoids quantified cell-type-specific identity, regional specification, maturation, and transcriptional fidelity to native tissue. The HGCA V1 provides a standardized cellular, anatomical coordinate, and metadata system for reproducible, high-quality analysis of intestinal biology across healthy tissue, disease-associated remodelling, and experimental models, providing a continuously evolving community reference for cumulative discovery in human intestinal biology.
Kimler K, Lance C, Bohar B, Ahmed A, Zhou R, Bartolome-Casado R, Gudino V, Ramirez Flores RO, Junghus FV, Morbe UM
Pregnancy & Reproductive Health (2 papers)
Impact of in vitro fertilization on disease activity and pregnancy outcomes in women with inflammatory bowel disease.★ Inflammatory bowel diseases | 2026-11-10
Women with inflammatory bowel disease (IBD) increasingly utilize assisted reproductive technologies (ARTs) like in vitro fertilization and oocyte cryopreservation. Data regarding ART associated IBD flare risk are limited. We evaluated the risk of disease exacerbation among women with IBD undergoing ART. This retrospective single-center study evaluated women with IBD undergoing ART. Electronic medical records were abstracted for demographics, IBD history, and fertility history. Disease activity was assessed via medication exposure, biomarkers, and healthcare utilization 6 months pre- and post-ART. The primary outcome was disease flare (therapy modification, steroid initiation, or IBD-related hospitalization) within 6 months of ART. Secondary outcomes included successful egg retrieval, biochemical pregnancy, and live birth. Demographics were analyzed at the patient level and outcome data at the ART encounter level. We included 49 women (mean age 37.1 ± 4.01 years, body mass index 25.7 ± 4.72 kg/m2) who underwent 149 ART encounters. Most had Crohn’s disease (63.3%) or ulcerative colitis (34.7%), with a mean disease duration of 13.4 ± 7.16 years. Pre-ART, therapies included ustekinumab (20.8%), anti-tumor necrosis factors (12.1%), and corticosteroids (6.7%), or no therapy (29.5%). In 149 ART encounters (86 oocyte retrievals and 63 embryo transfers), the overall disease flare rate was 3.4% (n = 5 of 149, representing 5 unique patients). Flares occurred after embryo transfer during established pregnancy (gestational week ≥8), with no flares occurring during or immediately following oocyte retrieval. Secondary endpoints showed low rates of new corticosteroid use (2.7%), IBD-related hospitalizations (0.7%), and medication dose escalation (0.7%). Among the 63 embryo transfers, biochemical pregnancy occurred in 63.5% (n = 40 of 63) and live births in 42.9% (n = 27 of 63). Across all 149 ART encounters, patients with IBD demonstrated low flare risk and live birth rates comparable to the general population. Under multidisciplinary guidance, ART is a safe and viable option in IBD.
Khanna R, Garcia NM, Fenton C, Long M, Mahadevan U
Trends in common laboratory markers during pregnancy in women with IBD in clinical remission.★ Inflammatory bowel diseases | 2026-11-05
Physiologic pregnancy changes can alter commonly monitored laboratory values and mimic active inflammatory bowel disease (IBD), complicating prenatal disease monitoring. Biomarker trajectories in women with IBD in remission are not well established. We aimed to characterize trimester-specific changes in key biomarkers among women with IBD in remission before and throughout pregnancy. We performed a retrospective review of pregnant women with IBD in remission enrolled in a prospective preconception/pregnancy registry. Eligible patients had laboratory data from the preconception period and at least 1 trimester (first trimester [T1], second trimester [T2], or third trimester [T3]). Parameters included complete blood counts, albumin, C-reactive protein, erythrocyte sedimentation rate (ESR), iron studies, and fecal calprotectin (FC). Changes from preconception were assessed using Wilcoxon signed rank tests and McNemar’s test when applicable. Sixty-eight pregnancies from 61 women were included (68.9% Crohn’s disease, 27.9% ulcerative colitis; median age 33 years; 83.8% on biologics). Compared with preconception, ESR and white blood cell count rose across trimesters (ESR PT2T3 < .001; white blood cell PT1-T3 < .001). Hemoglobin, hematocrit, platelets, and albumin declined significantly, particularly in T2/T3 (all P ≤ .008). C-reactive protein rose during all trimesters (PT1 = .003; PT2, T3 < .001), whereas FC remained stable and within normal range throughout pregnancy (all P > .05). Most biomarkers trended toward baseline postpartum. In pregnant women with IBD in remission, most laboratory changes appear physiologic, requiring cautious interpretation. FC was the only stable biomarker throughout pregnancy and remains the most reliable marker of inflammation during this period. These trimester-specific data may improve interpretation of biomarkers in pregnant patients with IBD.
Gottlieb ZS, Glamour B, Helmus D, Dubinsky MC
Intestinal Ultrasound (IUS) (1 papers)
Intestinal Ultrasound in Inflammatory Bowel Disease: From Point-of-Care Assessment to Standardized Treat-to-Target Monitoring.Review The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology | 2026-10-22
Intestinal ultrasound (IUS) is transitioning from a supplementary imaging technique to a reliable, point-of-care method for the objective monitoring of inflammatory bowel disease. Its clinical significance lies in its ability to directly assess bowel wall and extramural inflammation. It does not involve ionizing radiation, is well tolerated by patients, and can be used for disease reassessment during routine follow-up visits. The most reproducible markers of inflammatory activity are bowel wall thickness and color Doppler signal. Bowel wall stratification and the presence and extent of inflammatory mesenteric fat, strictures, and penetrating complications provide additional information on disease phenotype. Standardized instruments, including the International Bowel Ultrasound Segmental Activity Score for Crohn’s disease and the Milan Ultrasound Criteria for ulcerative colitis, improve comparability. Serial IUS examinations can assess treatment response within weeks and may identify residual or recurrent inflammation even when clinical improvement is attained. However, transmural healing remains an adjunctive target rather than an established treatment goal because clinical trials demonstrating that IUS-guided treatment escalation improves long-term outcomes are lacking. Broader implementation of IUS depends on standardized image acquisition and reporting, harmonized response definitions, competency-based training, and integration of IUS with symptoms, biomarkers, gastrointestinal endoscopy, and magnetic resonance enterography.
Rimbaș M, Furfaro F
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