IBD Literature Report
Coverage: March 23, 2026 - March 30, 2026
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Therapeutics & Mechanisms (23 papers)
Efficacy and Safety of Second-Line Advanced Therapy After Vedolizumab in Ulcerative Colitis: A Multicenter Cohort Study From the GETAID.Multicenter study★ United European gastroenterology journal | 2026-04
Vedolizumab has become the preferred first-line advanced therapy in ulcerative colitis (UC). However, the optimal second-line treatment following vedolizumab failure remains unclear. We aimed to evaluate the effectiveness and safety of second-line therapies after first-line vedolizumab. We conducted a multicenter retrospective study including UC patients from 31 centers who received infliximab (IFX), subcutaneous (SC) anti-TNFs, or ustekinumab after vedolizumab failure. The primary endpoint was steroid-free clinical remission (SFCR) at week 14. Predictors of remission were identified using multivariate logistic regression. Among 196 patients, 99 received IFX, 27 anti-TNF SC, and 70 ustekinumab. At week 14, SFCR was achieved in 78 patients (39.8%): 38 (38.4%) with IFX, 8 (29.6%) with anti-TNF SC, and 32 (45.7%) with ustekinumab, with no significant difference between groups (p = 0.32). Median treatment persistence ranged from 8 to 9.2 months. Baseline corticosteroid use was associated with lower odds of SFCR (OR = 0.37, 95% CI [0.18-0.73]). Adverse events occurred in 15.8% of patients, including 12.2% serious events. Overall adverse events were less frequent with ustekinumab than with IFX (10.0% vs. 24.2%, p = 0.02), while serious events were comparable (5.7% vs. 16.1%, p = 0.08). Discontinuation due to adverse events was more frequent with IFX (12.1%) and anti-TNF SC (14.8%) than with ustekinumab (2.9%, p = 0.045 and 0.049). In UC patients failing vedolizumab, second-line IFX, anti-TNF SC, and ustekinumab showed similar effectiveness and persistence. Infliximab remains a robust option for rapid control in high inflammatory burden, whereas ustekinumab may be preferred for its superior safety profile in high-risk patients.
Calméjane L, Reenaers C, Gay C, Amiot A, Nuzzo A, Vuitton L, Atanasiu C, Stefanescu C, Altwegg R, Guillo L
Higher Colonic Tissue Drug Concentrations of Subcutaneous Compared to Intravenous Administration of Infliximab Therapy in Patients With Inflammatory Bowel Disease.Observational study★ United European gastroenterology journal | 2026-04
Intestinal tissue levels of infliximab (IFX) in patients with inflammatory bowel disease (IBD) treated with subcutaneous (SC) therapy have not been previously assessed. To compare serum and colonic tissue IFX concentrations in IBD patients receiving SC versus intravenous (IV) IFX. This observational cross-sectional study included IBD patients on stable SC or IV IFX maintenance therapy undergoing routine follow-up colonoscopy. Clinical activity required elevated CDAI or Mayo score plus ≥ 1 biomarker (fecal calprotectin > 250 μg/g or CRP > 5 mg/L). Blood samples and two colonic biopsies were collected for serum and tissue IFX measurements. Thirty-five patients were included. Serum and tissue IFX concentrations were significantly higher in the SC versus IV group (22 μg/mL vs. 9 μg/mL, p < 0.001; 25 μg/g vs. 10 μg/g, p = 0.002). Serum and colonic tissue IFX levels were positively correlated in both cohorts (IV: r = 0.42; p = 0.014; SC: r = 0.43; p = 0.001). Colonic tissue IFX concentrations were higher in patients with mild-moderate endoscopic activity than in those without active disease (p < 0.001). Serum and colonic tissue IFX levels both predicted sustained clinical remission, with optimal thresholds of 14.5 μg/mL (p = 0.015) and 17 μg/g (p < 0.005), respectively. Colonic tissue IFX showed higher predictive accuracy (AUROC 0.82, p = 0.01) than serum (AUROC 0.76, p = 0.045). SC IFX achieved significantly higher serum and colonic tissue concentrations than IV IFX. Colonic tissue IFX levels demonstrated superior clinical relevance and may support future tissue-based therapeutic drug monitoring strategies in IBD.
Roblin X, Nancey S, Papamichael K, Mechi F, Ouvrier-Buffet J, Charlois AL, Peaucelle AS, Bastide L, Berger AA, Barrau M
Personalised treatment in biologically naive patients with Crohn’s disease: a systematic review of the last 10 years.Review Scandinavian journal of gastroenterology | 2026-03-28
Biological treatment has revolutionised the management of Crohn’s disease (CD), however, at baseline (pre-treatment), it is not possible to predict which biologic a patient will respond the best to. This systematic review aimed to identify pre-treatment predictors of response/non-response to infliximab, adalimumab, vedolizumab and ustekinumab and to critically evaluate the available literature. We searched Embase, MEDLINE and Cochrane Registry of Controlled Trials (published from 2014 to 2024) for studies reporting on pre-treatment predictors of response/non-response to infliximab, adalimumab, vedolizumab, ustekinumab in adult (≥18 years) biologically naïve CD patients. Two reviewers independently completed title/abstract screening, full-text reading, data extraction, and quality assessment. The quality of the included studies was evaluated using ‘Prediction model Risk Of Bias ASsessment Tool’ (PROBAST). A total of 39 studies were eligible for final inclusion. Vedolizumab and ustekinumab were investigated in one study each. For infliximab and adalimumab, we found several potential predictors such as age, body mass index (BMI), disease duration and behaviour, C-reactive protein (CRP), interleukins (ILs) and different imaging characteristics, that could be integrated into future prediction model studies. All studies were judged high risk of bias (RoB) - mainly due to problems regarding analyses and outcome definitions and determinations. No pre-treatment predictors fulfilled the criteria of being an appropriate predictor of response/non-response. This was due to high RoB, conflicting results and a large heterogeneity between the studies. Future studies must be well-designed and follow strict protocols to produce robust results.
Buhl E, Kraaer MT, Kjeldsen J, Ainsworth MA
Therapeutic drug monitoring in inflammatory bowel disease patients switching from intravenous to subcutaneous infliximab: insights from a prospective real-world study. Scandinavian journal of gastroenterology | 2026-03-28
The efficacy and safety of switching from intravenous (IV) to subcutaneous (SC) infliximab (IFX) have been demonstrated across multiple studies, but data on patients treated with high IV doses remain limited. This study aimed to confirm the safety of switching regardless of IV dosing regimen and examine serum drug concentrations during follow-up. This prospective single-centre study included adult patients with inflammatory bowel disease in remission on maintenance IV IFX. Patients receiving IV IFX <1.5 mg/kg/week were assigned to 120 mg every 14 days, while those on ≥1.5 mg/kg/week received 240 mg. The target SC IFX serum range was 15-30 mg/L, with doses adjusted accordingly during follow-up. Among 267 patients, 93% were switched to standard SC dose and 7% to high dose. Remission rates remained stable over 6 months in both groups. Mean serum levels increased from 9.4 mg/L (IV) to 21.1 mg/L (SC) in the standard-dose group, and from 12.3 mg/L to 24.3 mg/L in the high-dose group. Serum IFX levels did not differ significantly by biochemical remission status. In multivariable linear regression, higher body mass index and previous intra-abdominal surgery were associated with lower serum IFX concentrations. Patients on IV IFX can be safely switched to SC treatment when initial dosing is guided by the prior IV regimen and subsequently individualized based on serum drug concentrations. Fixed SC dosing based solely on previous IV dosing may be appropriate for patients on standard IV doses but less reliable in those treated with higher doses.
Bergsmark C, Kristensen VA, Sjåmo MB, Høivik ML, Anisdahl K
Re-induction or Redirection? Lessons From the REScUE Trial on Ustekinumab Intensification in Crohn’s Disease.Editorial★ Gastroenterology | 2026-03-27
Matrine improves bile acid metabolism and reduces inflammatory and oxidative stress in colitis via the JAK2 pathway. Chinese medicine | 2026-03-26
Dysbiosis during colitis alters the conversion of primary to secondary bile acids by gut microbiota, which affects bile acid receptor signaling and may exacerbate mucosal inflammation in experimental colitis models. While the natural compound matrine has known anti-inflammatory properties, its therapeutic mechanism in colitis remains unclear. This study aims to elucidate matrine’s potential by identifying its molecular targets and effects in colitis. Bioinformatics and molecular docking were used to identify potential drug targets. A multi-model approach was then employed, using a dextran sulfate sodium (DSS)-induced murine model of colitis, a lipopolysaccharide (LPS)-stimulated intestinal epithelial cell model, and clinical colon and serum samples from ulcerative colitis (UC) patients. The effects of matrine on inflammatory cytokines, oxidative stress markers, and bile acid levels were detected using ELISA and various commercial kits. Intracellular reactive oxygen species (ROS) were measured by flow cytometry. JAK2 as a key hub target for matrine, and molecular docking predicted a direct binding interaction. The JAK2 level was found to be upregulated, while bile acid transporters and overall serum bile acid levels were decreased in human UC patients and correlated negatively with disease severity. In a DSS-induced murine model of colitis, matrine treatment mitigated disease symptoms, reduced key inflammatory markers (IL-1β, TNF-α, IL-6) and oxidative stress indicators (including ROS), and restored bile acid homeostasis by upregulating transporters (MRP3 and MRP4) and bile acid receptor FXR. Critically, the mechanism was confirmed to be JAK2-dependent in vitro; experiments demonstrated that JAK2 overexpression alone was sufficient to induce pathology and that it completely reversed the therapeutic effects of matrine. This study is the first to comprehensively demonstrate that matrine directly targets the JAK2/STAT3 signaling axis to restore bile acid homeostasis and suppress inflammation in experimental colitis with validation in human UC patients, providing novel mechanistic and translational insight into how matrine may benefit colitis.
Jiang ZX, Chen XL, Sun Q, Yang LC, Zhang YW, Wu Q, Yao HC, Zhang D, Yuan LW
Outcomes of Risankizumab in Patients with Crohn’s Disease and Prior Ustekinumab Exposure in a Multicenter Academic Institution. Digestive diseases and sciences | 2026-03-25
Risankizumab (RZB) and ustekinumab (UST) are interleukin inhibitors that are used for the treatment of moderate-to-severe Crohn’s disease (CD). Data on outcomes of RZB in patients previously treated with UST are limited. We aim to evaluate the efficacy of RZB in patients previously exposed to UST. This retrospective study included adult patients with CD who were prescribed RZB and had prior UST exposure at a multicenter academic institution between 1/2022 and 8/2024. We extracted demographic, CD-related, and medication-related data, as well as subjective and objective endpoints while on UST and RZB. Fisher’s exact test and the Wilcoxon rank-sum test were used in the analysis. Among 68 patients treated with RZB and prior UST therapy, 43 (63.2%) experienced symptomatic improvement on RZB, 57 (83.8%) avoided surgery, and 12 of 25 patients on steroids (48%) achieved steroid-free remission. Average C-reactive protein, fecal calprotectin, and endoscopic scores decreased on RZB compared with UST. A higher number of previous CD medications was associated with a lack of improvement on RZB (p = 0.011). Secondary nonresponse to UST was significantly associated with improvement on RZB (p = 0.047). No difference in RZB response was observed between patients maintained on standard UST dosing and those who underwent dose escalation (p = 0.557). RZB appears to be an effective treatment option for patients with CD and prior UST use, particularly those with secondary loss of response. A higher number of previously trialed therapies was associated with reduced likelihood of response, underscoring the importance of early, strategic treatment sequencing.
Vattikonda A, Odah T, Crosby S, Hashash JG, Kinnucan JA, Picco MF, Farraye FA
Short and medium-term outcomes of ustekinumab biosimilar in patients with Crohn’s disease in naïve patients and after switching from originator. Revista espanola de enfermedades digestivas | 2026-03-25
Recently ustekinumab biosimilar has been aproved for the treatment of patients with Crohn’s Disease. This retrospective bicentric study aimed to evaluate the short- and medium-term effectiveness and safety of UB in ustekinumab-naïve patients and after switching from the originator.
Fuentes-Valenzuela E, Chivato Martín-Falquina I, Olmos Jerez JA, López-Martín MDC, Calvache A, Gil Santana M, Castaño Milla C, Bejerano Domínguez A
Risk of Autoimmune Hepatitis Among Patients with Inflammatory Bowel Disease Treated with Infliximab: A Retrospective Cohort Study Using a National Database. Digestive diseases and sciences | 2026-03-25
Infliximab and adalimumab are widely used anti-tumor necrosis factor agents for inflammatory bowel disease, both with reported cases of drug-induced autoimmune hepatitis. However, comparative data on the risk of autoimmune hepatitis with infliximab versus adalimumab are limited. We aimed to compare the risk of autoimmune hepatitis among patients with inflammatory bowel disease treated with infliximab versus adalimumab. We conducted a retrospective active-comparator, new-user cohort study using the TriNetX US collaborative network. Adults with Crohn’s disease or ulcerative colitis who initiated infliximab or adalimumab were included. Patients with prior autoimmune hepatitis, prior exposure to the alternate anti-tumor necrosis factor agent, selected autoimmune comorbidities, or other biologic exposure were excluded. The primary outcome was new autoimmune hepatitis occurring at least 3 months after treatment initiation. Propensity score matching was performed to balance baseline covariates. A sensitivity analysis was also conducted including autoimmune comorbidities in the matching model. After propensity score matching, 15,298 patients remained in each group. Autoimmune hepatitis occurred in 33 patients (0.216%) treated with infliximab and 13 patients (0.085%) treated with adalimumab. Infliximab was associated with a higher risk of autoimmune hepatitis (risk ratio 2.53; 95% confidence interval (CI) 1.336-4.818; P = 0.0032). Time-to-event analysis showed similar findings (hazard ratio 2.602; 95% CI 1.369-4.945). In the sensitivity analysis, infliximab remained associated with a higher risk of autoimmune hepatitis. In this large national cohort of patients with inflammatory bowel disease, infliximab was associated with a higher observed risk of autoimmune hepatitis compared with adalimumab.
Almusabeh H, Kovach Z, Lloyd L, Alzaher MZ, Teran D, Adeniran O, Shepherd K, Elfert K, Goswami S, Tandon K
Analysis of possible baseline and treatment-course factors associated with non-remission in patients with Crohn’s disease treated with ustekinumab: a retrospective real-life analysis. Pharmacological reports : PR | 2026-03-24
Abstract not available.
Tursi A, Pellegrino R, Mocci G, Elisei W, Scaldaferri F, Savarino EV, Maconi G, Bodini G, Papa A, Gravina AG
Serious Infection in Crohn’s Disease Patients Treated With Ustekinumab: US Food and Drug Administration Active Postmarket Risk Identification and Analysis in the Sentinel Initiative. Clinical pharmacology and therapeutics | 2026-03-24
The U.S. Food and Drug Administration (FDA) used an Active Postmarket Risk Identification and Analysis (ARIA) system to address a safety issue (serious infection) identified during clinical review of an application to market ustekinumab as a treatment for Crohn’s disease (CD). FDA used an active-comparator new-user cohort design, data from six Sentinel Data Partners, a method developed in Sentinel for identifying serious infection, and ARIA analytic tools to estimate serious infection incidence in adult CD patients during treatment with ustekinumab or an active comparator (infliximab, adalimumab, or vedolizumab). Inverse probability of treatment weighting (IPTW) was used to control for baseline differences between treatment groups. Analyses compared ustekinumab and comparator cohorts with 15,490 and 51,503 patients, respectively. The primary composite outcome of serious infection or COVID-19 occurred in 747 ustekinumab patients (4.82 %; 44.1 per 1000 patient-years) during mean 400-day follow-up. IPTW proportional hazard (Cox) regression estimated risk in the ustekinumab cohort vs. active comparator with hazard ratio 0.88 (95% confidence interval 0.80-0.96). Findings were similar (a) according to line of therapy (use or non-use of an advanced inflammatory bowel disease therapy during a 183-day baseline period) and (b) before and after the start of the COVID-19 pandemic. Additional analyses excluded large magnitude risks from ustekinumab for major types of serious infection. In conclusion, IPTW analyses excluded large magnitude risks from ustekinumab for serious infection. This report describes the first ARIA study to use complex confounding adjustment to help resolve a safety issue identified during FDA review of a marketing application.
Weissfeld JL, Iyer GS, Seo SC, Giffin A, Simon AL, Kluberg SA, Hoffman ER, Jones JT, Dutcher SK, Korvick JA
Performance evaluation of an adalimumab biosimilar autoinjector and its reference device: comparative use human factors study in patients with rheumatoid arthritis and juvenile idiopathic arthritis.Multicenter study Drug delivery | 2026-03-24
A Comparative Use Human Factors study was conducted to assess whether the injection success rate (SR) with biosimilar adalimumab-fkjp (Bios-ADA) autoinjector (Hulio®) is comparable to reference adalimumab (Ref-ADA) autoinjector (Humira®), accounting for design differences, including the absence of an activation button, to evaluate usability in the target patient population. A counterbalanced, multicenter study was conducted under simulated conditions, with patients completing multiple steps to administer the medication (40 mg Bios-ADA or Ref-ADA) into an injection pad using both devices. The endpoint was the overall SR for completing critical delivery system tasks with each device. A total of 55 patients (50 adults with rheumatoid arthritis and five patients with juvenile idiopathic arthritis and/or pediatric Crohn’s disease) were enrolled. The overall SR for patients using the Bios-ADA autoinjector and the Ref-ADA was 92.7% (51/55) and 87.3% (48/55), respectively. Four and seven use errors were observed with the Bios-ADA and Ref-ADA autoinjectors, respectively. Bios-ADA autoinjector was non-inferior to Ref-ADA autoinjector, and design differences did not introduce clinically significant use-related risks. The Bios-ADA autoinjector can be used as a practical alternative to the Ref-ADA autoinjector from a usability perspective, with comparable overall performance during self-administration.
Moses K S, Konda Ramachary Subramanian S
Efficacy and health-related quality of life associated with second-line vedolizumab after first-line treatment with one anti-TNF in patients with ulcerative colitis: a meta-analysis of the GEMINI-1 and VISIBLE-1 trials. Therapeutic advances in gastroenterology | 2026-03-23
Vedolizumab is a monoclonal antibody approved for adults with moderately to severely active ulcerative colitis and an inadequate response/intolerance to conventional, or anti-tumor necrosis factor (TNF) treatment. Additional efficacy data for second-line vedolizumab after first-line anti-TNF treatment are required to determine its optimal position in the treatment sequence. To evaluate efficacy and health-related quality of life (HRQoL) associated with second-line vedolizumab after first-line anti-TNF in patients with ulcerative colitis. Meta-analysis. Data from randomized, placebo-controlled phase III trials (GEMINI-1 (NCT00783718) and VISIBLE-1 (NCT02611830)) were used. Patients who received second-line vedolizumab after first-line anti-TNF treatment within 5 years before trial enrollment were included. The primary outcome was clinical remission with two definitions based on the adapted Mayo score. Secondary outcomes were corticosteroid (CS)-free remission, Mayo endoscopic score (MES) ⩽1, and HRQoL (Inflammatory Bowel Disease Questionnaire and EuroQoL-5 Dimension Visual Analog Scale). Outcomes were assessed at Week 52. Efficacy of vedolizumab versus placebo was compared using fixed-effects models. Regression analyses assessed treatment effects, adjusting for disease location/duration and previous CS use. Overall, 137 patients from GEMINI-1/VISIBLE-1 were included. Patient characteristics were similar across cohorts, although mean disease duration ranged from 6.6 to 9.9 years. Second-line vedolizumab was associated with a higher likelihood of achieving both definitions of clinical remission and all secondary outcomes (CS-free remission, MES ⩽1, and HRQoL) versus placebo. Regression analysis showed that patients treated with vedolizumab were 7.13-11.35 times more likely to achieve clinical remission (both definitions) versus placebo. Second-line vedolizumab after first-line anti-TNF treatment significantly increased the likelihood of achieving clinical remission, MES ⩽1, and improved HRQoL at Week 52 versus placebo in patients with ulcerative colitis. The small sample size, associated limitations, and heterogeneity observed in some outcomes warrant further research to strengthen these findings. A combined analysis of two studies to assess how well vedolizumab works in patients with ulcerative colitis, who first received anti-tumor necrosis factor treatment Ulcerative colitis (UC) is a chronic condition that affects the lining of the large intestine. Many drugs are available for patients with UC to receive, including a type of drug called biologics. Anti-tumor necrosis factor (TNF) is often the first biologic given to patients with UC, known as first-line treatment. Some patients may require a different treatment if the first-line treatment doesn’t work well enough, or causes side effects. Vedolizumab is another biologic that can be used by patients with UC. More data are needed on vedolizumab as a second treatment, known as second-line, to find out the best order of biologics for patients with UC. This study assessed how well second-line vedolizumab worked, known as the efficacy, and its effect on patients’ quality of life. Data were gathered from two clinical trials of patients with UC who had previously received first-line anti-TNF treatment and went on to receive second-line vedolizumab. A process called a meta-analysis was used to combine the data from these studies and assess different outcomes. The main outcome assessed was whether patients’ disease improved after a year of treatment, known as clinical remission, compared with patients who received a placebo. The meta-analysis tested this outcome and adjusted for factors such as how long the patient had UC. A total of 137 patients were included. Patients in the vedolizumab treatment groups and placebo groups had similar characteristics. The meta-analysis showed that patients who received second-line vedolizumab were significantly more likely to reach clinical remission after 1 year of treatment than patients who received a placebo. Patients who received second-line vedolizumab also had small improvements in quality-of-life measures. These results provide evidence that can help guide decisions about the order of treatments, but further research is needed to strengthen the findings.
Atreya R, Kirchgesner J, Cheah Z, Biedermann P, Bakker L, Meyer M, Raine T
Multiomic characterisation of the clinical efficacy of guselkumab induction therapy in ulcerative colitis.RCT BMJ open gastroenterology | 2026-03-23
Selective inhibition of interleukin (IL)-23 through antagonism of the IL-23p19 subunit has demonstrated clinical efficacy in inflammatory bowel disease, but the molecular changes underlying the efficacy outcomes have not yet been described. Here, we provide a detailed evaluation of the cellular and molecular changes associated with guselkumab treatment in patients with moderately to severely active ulcerative colitis (UC) from the QUASAR Phase IIb induction study. In this double-blind, placebo-controlled, dose-ranging induction study, patients (n=313) were randomised (1:1:1) to receive intravenous guselkumab 200 or 400 mg or placebo at weeks 0, 4, and 8. Colon biopsy samples were collected at weeks 0 and 12, enabling molecular profiling by bulk RNA sequencing (RNA-seq, n=257), single-cell RNA sequencing (n=52), and flow cytometry (n=30). Serum proteomic profiling was also performed at weeks 0, 4, and 12 (n=302). Guselkumab treatment significantly reduced pro-inflammatory serum proteins by week 4 with continued decline through week 12, compared with placebo. Unsupervised analysis of tissue gene modules revealed significant changes in transcriptional states related to pro-inflammatory and epithelial repair pathways, which were most pronounced in patients who achieved histological-endoscopic mucosal improvement (HEMI) at week 12, an important tissue-based end point. Single-cell analyses supported a decrease in the cellular abundance of pro-inflammatory and an increase in mucosal cell types in tissue following treatment. This analysis of guselkumab in UC demonstrated changes in key pathways and cell types that are associated with achieving important clinical end points including HEMI at week 12. NCT04033445.
Hart A, Sridhar S, Venkat S, Lee T, Rusbuldt JJ, Richards D, Sisk C, Horowitz D, Tomsho L, Kannan AK
Lower drug clearance of adalimumab is associated with proactive therapeutic drug monitoring and mucosal healing in patients with inflammatory bowel disease. European journal of gastroenterology & hepatology | 2026-03-23
There are limited data regarding adalimumab (ADM) clearance in inflammatory bowel disease (IBD). The aim of this study was to identify factors associated with ADM clearance and to assess its association with mucosal healing. This single-center, retrospective study included consecutive patients with IBD who received maintenance ADM therapy and underwent therapeutic drug monitoring (TDM) between January 2018 and May 2023. Drug clearance was determined using a nonlinear mixed-effect model with Bayesian priors. Mucosal healing was defined as an endoscopic Mayo score 1 or less; for ulcerative colitis, no ulcerations for patients with Crohn’s disease, or a Rutgeerts score of i1 or less for patients with an ileocolonic resection for Crohn’s disease and was evaluated within 3 months from TDM. The study population consisted of 263 patients with IBD (74% Crohn’s disease) who underwent a total of 515 TDM tests (388 proactive). Multivariable linear regression analysis identified that proactive TDM was associated with lower ADM clearance [beta coefficients (β): -0.173, 95% confidence interval (CI): -0.180 to -0.088, P < 0.001], while BMI (β: 0.125, 95% CI: 0.005-0.013, P < 0.001), prior biologic exposure (β: 0.087, 95% CI: 0.022-0.112, P = 0.004), and antibodies to ADM (β: 0.676, 95% CI: 0.628-0.750, P < 0.001) were associated with higher ADM clearance. Receiver operating characteristic analysis identified an ADM clearance threshold of 0.301 L/day (area under the receiver operating characteristic curve: 0.731; 95% CI: 0.654-0.808; P < 0.001; sensitivity: 61%; specificity: 78%) distinguishing patients with or without mucosal healing. This study demonstrated that lower ADM clearance is associated with proactive TDM and mucosal healing in patients with IBD.
Deyhim T, Saraga A, Gade A, Geeganage G, Soliman MA, Zullow S, Rabinowitz LG, Grossberg LB, Cheifetz AS, Dervieux T
Additive effects of fecal microbiota transplantation and infliximab on gut microbiome and metabolome in refractory inflammatory bowel disease patients. mSystems | 2026-03-23
Fecal microbiota transplantation (FMT) is an emerging therapy for inflammatory bowel disease (IBD), yet its efficacy in patients refractory to conventional treatments and its underlying mechanisms require further elucidation. We studied 37 IBD patients (15 ulcerative colitis [UC], 22 Crohn’s disease [CD]) refractory to conventional therapies and 16 healthy donors. FMT monotherapy from a single donor induced week-4 clinical response in 12 UC and 9 biologic-naïve CD patients, with all responders sustaining remission and most achieving endoscopic remission by week 14. Integrated multi-omics revealed FMT restored microbial diversity and profoundly reorganized host-microbiota-metabolite networks. In nine refractory CD patients (7 infliximab [IFX] non-responders, 2 FMT non-responders), IFX-FMT combination led to week-4 response in 6 patients, all of whom attained clinical and endoscopic remission by week 14, with more complete microbial-metabolic restoration than monotherapy. Our findings establish that FMT induces remission in refractory IBD via ecosystem network rewiring, and that IFX-FMT exhibits additive effects, supporting further trials of microbiome-directed adjunctive strategies. This study provides mechanistic and clinical insights into the therapeutic effects of fecal microbiota transplantation (FMT) in inflammatory bowel disease (IBD), particularly when combined with the anti-tumor necrosis factor (anti-TNF) biologic infliximab (IFX). While both FMT and IFX achieve response in approximately 60% of IBD patients, their combined influence on the gut microbial and metabolic landscape in refractory disease has been poorly understood. Here, we demonstrate that FMT monotherapy restores gut microbial diversity and reconfigures host-microbiota-metabolite networks, correlating with clinical and endoscopic remission in patients refractory to conventional treatments. Furthermore, in Crohn’s disease patients unresponsive to either therapy alone, combined IFX-FMT induced more complete microbial and metabolic normalization and achieved remission where monotherapy had failed. These findings reveal ecosystem-level network rewiring as a central mechanism of FMT efficacy and establish the additive potential of combining microbiome-targeted and immunomodulatory therapies. This work supports the development of microbiome-informed adjunctive strategies for severe or refractory IBD, highlighting an actionable path toward personalized, mechanism-based treatment regimens. This study is registered with ClinicalTrials.gov as NCT07149441.
Wang X, Wu W, Yang B, Liu Y, Xu Y, Wang L, Lv X, Gao J, Lu M, Yu A
Advancing drug discovery for Inflammatory bowel diseases through human intestinal organoid-based models.Review Expert opinion on drug discovery | 2026-03-23
Inflammatory bowel diseases (IBD), including Crohn’s disease and ulcerative colitis, are chronic inflammatory conditions that affect millions of patients worldwide. Despite recent advances, the available IBD drugs targeting the immune system have limited efficacy, and disease recurrence is common. In this review, the authors describe reported applications of human intestinal organoids to understand the mechanisms of actions and predict patient response to current IBD therapies. Furthermore, they also outline the potential of human intestinal organoid-based technologies to accelerate drug discovery in IBD and propose a framework to bridge discoveries from the bench to the bedside. The lag in the development of novel IBD therapies reflects the complex nature of the disease and our poor understanding of its pathogenesis. The future breakthrough in understanding IBD and developing novel IBD drugs require development and adaptation of novel disease-relevant experimental models, including organoid-based models, to evaluate the efficiency and accurately predict response to therapy. Indeed, presently the utilization of intestinal organoids in the IBD field has been limited and were not used in the development of any of the currently available therapies, including biologics (anti-TNF, anti-12/IL23, anti-α4β7) and small molecules. The authors affirm that a stepwise approach would help accelerate future organoid-based drug discovery efforts.
Braga Neto MB, Jatana S, Rieder F, Ivanov AI
Orally deliverable Perilla frutescens-derived nanovesicles as natural bioactive nanocarriers for colon-targeted colitis therapy via microenvironment reprogramming. Biomaterials advances | 2026-03-20
Effective oral therapy for inflammatory bowel disease (IBD) requires overcoming gastrointestinal barriers to modulate the dysregulated mucosal niche. Here, we present edible nanovesicles derived from Perilla frutescens (PLENs) as an intrinsically stable, bioactive nanotherapeutic. Multi-omics profiling defined a robust lipid-bilayer architecture encapsulating a synergistic cargo of proteins, miRNAs, and antioxidant metabolites. This structural integrity enabled PLENs to survive gastrointestinal transit and exhibit preferential fluorescence localization with prolonged retention in the inflamed colonic region, as indicated by in vivo imaging. Upon localization, PLENs executed a “dual-hit” therapeutic strategy: they reprogrammed the immune microenvironment, accompanied by reduced activation of the TLR4/MyD88-NF-κB axis and a phenotypic shift from pro-inflammatory M1 to reparative M2 macrophages. Concurrently, PLENs fundamentally restructured the gut ecosystem, accompanied by enrichment of taxa linked to saccharolytic fermentation and recovery of cecal short-chain fatty acids. Notably, fecal microbiota transplantation (FMT) further supported that this microbial remodeling contributed to the protective phenotype, highlighting the microbiome as an important component of efficacy.
Yang Z, Zhang F, Yang S, Anayyat U, Mo Y, Ying Y, Wang X
Quantification of visceral adipose tissue volume predicts both short-term and long-term transmural healing in patients with Crohn’s disease receiving Ustekinumab. Therapeutic advances in gastroenterology | 2026-03-15
Transmural healing (TH) is an emerging therapeutic target in Crohn’s disease (CD). Visceral adipose tissue (VAT) is associated with the prognosis of CD, but few studies investigate the ability of VAT in predicting TH. We aimed to quantitatively assess VAT by magnetic resonance enterography (MRE) and evaluate the prediction of baseline VAT volume for TH in CD patients with Ustekinumab (UST) treatment. This is an observational study. We retrospectively included CD patients receiving UST treatment, with bowel wall thickness (BWT) >3 mm assessed by MRE at baseline. Clinical characteristics, laboratory, endoscopic, and MRE indicators were evaluated at baseline, week 26 (W26), and week 78 (W78) of the therapy. Quantification of VAT volume was assessed by MRE at baseline, and adjusted by body mass index (BMI). The TH was defined as BWT ⩽3 mm without any signs of inflammation at W26 and W78. Sixty-two patients were included in our study. After UST treatment for W26 and W78, 8 (13.1%) and 13 (21.0%) patients achieved TH. Compared with baseline, laboratory indicators such as C-reactive protein and erythrocyte sedimentation rate, simple endoscopic score for CD, and BWT were significantly improved at W26 and W78. We divided patients into the TH and non-TH groups at both W26 and W78, and found that adjusted VAT volume at baseline was significantly lower in the W26-TH and W78-TH groups. Adjusted VAT volume was then categorized into four scores by quartiles, and multivariable analysis showed that baseline VAT score could negatively predict W26-TH (odds ratio (OR) = 0.296, p = 0.018) and W78-TH (OR = 0.419, p = 0.012). Our study demonstrated that baseline VAT was an independent risk factor for predicting both short- and long-term TH in CD patients receiving UST. Patients with lower VAT volume at baseline were more likely to achieve TH after UST treatment.
Wu X, Fan C, Duan X, Feng Z, Li X, Chen M, Wang Y, Zheng Q, Mao R
Curcumin-Loaded Lactoferrin/Pectin Core-Shell Structured Microgel Nanoparticles: Dual Regulatory Effects in Alleviating Inflammatory Bowel Disease. Nutrients | 2026-03-14
Curcumin (Cur) has therapeutic potential for inflammatory bowel disease (IBD) but is limited by its poor bioavailability. This study demonstrated that Cur-loaded core-shell structured microgel nanoparticles (LF/CP-Cur MN), fabricated through electrostatic complexation between lactoferrin and citrus pectin, followed by Ca2+ consolidation, overcome this limitation. These nanoparticles effectively reduced the bitterness and astringency of curcumin while prolonging its release time. In an IBD mouse model, LF/CP-Cur MN treatment mitigated symptoms and inflammation of IBD, and restored intestinal barrier integrity. Crucially, compared with free Cur, the LF/CP-Cur MN enhanced colon-targeted accumulation of Cur and favorably modulated the gut microbiota by increasing beneficial genera like Lactobacillus and Dubosiella, while suppressing harmful genera like Enterobacter, thereby promoting levels of acetate, propionate, and butyrate. These findings highlight the potential of the LF/CP-Cur MN to improve Cur bioaccessibility and exert dual functional roles in modulating gut microbiota and alleviating inflammation, thus offering a promising dietary strategy for the management of IBD.
Jin MY, Yu SY, Wang EF, Zhang H, Xu JY, Wang C, Li LQ, Yan JK
Early proactive therapeutic drug monitoring with ustekinumab therapy in pediatric Crohn’s disease: data from the prospective Canadian children IBD network. Crohn’s & colitis 360 | 2026-03-11
Ustekinumab dosing information for pediatric Crohn’s disease (CD) is limited. To examine ustekinumab pharmacokinetic and effectiveness data in a largely bio-naïve cohort, focusing on early (week 8) levels. Children in the prospective Canadian Children IBD Network initiating intravenous (IV) ustekinumab for CD with a week 8 level were evaluated. Disease activity was assessed by corticosteroid-free clinical remission (CSFR), biochemical CSFR, and mucosal healing (MH) by colonoscopy or fecal calprotectin <150 µg/g beyond 16 weeks. We compared drug levels by weight group (</≥40kg) and outcome, using receiver-operating characteristic (ROC) curves to identify optimal week 8 levels. Amongst 58 children (19 < 40 kg, 81% bio-naïve, median (interquartile range [IQR]) follow-up 11.5 [7.6-16.0] months), the IV loading dose for those <40kg (median 9.1 [8.6-10.2] mg/kg; 253 (239-268) mg/m2) was greater than for those ≥40kg (median 6.1 [5.4-6.5] mg/kg; 218 ([78-237] mg/m2, P < .001). However, week 8 levels were similar (P = .26). This was most striking in those with low albumin. Of 34/58 (59%) without escalation to 4 weekly dosing, 43%, 35%, and 19% exhibited CSFR, biochemical CSFR, and MH, respectively, during established maintenance. Median week 8 levels were roughly 5-6 µg/g vs 7-10 µg/g in patients not achieving vs achieving favorable outcomes, while ROC analysis indicated levels 8-9 µg/mL were associated with improved outcomes. Children <40 kg required more IV ustekinumab (median 9 mg/kg; 250 mg/m2) to achieve similar week 8 levels as children ≥40kg receiving conventional adult 6 mg/kg weight-tiered induction. Higher week 8 levels were associated with favorable later outcomes.
Ricciuto A, McKay HE, deBruyn JC, Crowley E, Church PC, Huynh HQ, Otley AR, Shaikh A, Mack DR, Carman N
Biomarker-Guided Drug Delivery Systems and Oral Bioavailability Enhancement.Review Pharmaceuticals (Basel, Switzerland) | 2026-03-11
Biomarker-based guided delivery of drugs is an emerging paradigm of precision medicine in which targeted therapeutic intervention is administered on the basis of certain biological markers in order to achieve maximal dosing, targeting, and time optimization. By utilizing quantifiable physiological or molecular signatures like the expression of transporters, enzymatic activities, metabolite levels, or disease-specific markers to tie in the correlation of drug disposition, these systems provide individualized intervention with optimized efficacy and safety. Oral administration of drugs is still the best route in patient compliance; however, several drugs are handicapped by suboptimal bioavailability secondary to poor solubility, limited permeability, efflux transporter participation, and enzymatic first-pass degradation. These result in variable therapeutic results in patient populations. Biomarker guidance in oral drug delivery provides a potent strategy for overcoming such challenges through site-specific release, real-time dose optimization, and adjustment of absorption pathways. Recent developments include pH-controlled formulations for gut-specific targeting, enzyme-activated nanocarriers, glucose-starved responsive devices for metabolic disease, and biomarker-driven transporters for permeability enhancement. Preclinical and early-phase clinical studies hold promising prospects for applications in oncology, infectious disease, inflammatory bowel disease, and metabolic disease. While promising momentum exists, transition to routine use in the clinic awaits rigorous biomarker validation, scalability in manufacture, and regulations harmonization. On the horizon, the integration of biomarker-guided oral drug delivery with nanotechnology, artificial intelligence, machine learning, and wearable biosensors holds promise for revolutionizing oral therapy into very personalized, responsive, and efficient treatment methods.
Vo DK, Duong VA
Viral encephalitis related to adalimumab in a 16-year-old Crohn’s disease patient: case report and literature review.Case report Frontiers in immunology | 2026-03-10
Tumor necrosis factor-alpha (TNF-α) inhibitors are extensively utilized in inflammatory bowel disease (IBD). Adalimumab (ADA), a TNF-α inhibitor, appears to be an effective and safe option for pediatric Crohn’s disease (CD), but the potential risk of opportunistic infection and autoimmune disease is of particular concern. We present the first pediatric case of viral encephalitis (VE) in a 16-year-old boy with CD following treatment with ADA. A 16-year-old CD patient developed symptoms such as fever, dizziness, drowsiness, and blurred vision after three months of ADA treatment. Fundoscopic examination demonstrated pronounced edema of the optic disc in both eyes. The lumbar puncture revealed a marked elevation in intracranial pressure and pathogen analysis of the cerebrospinal fluid identified an HHV-7 infection using next generation sequencing. Following discontinuation of ADA and treatment with acyclovir, the child’s symptoms largely subsided. Literature search identified 11 published CD adult patients with neurological complications related to ADA treatment, while 7 cases were diagnosed with autoimmune encephalitis and 4 with Guillain-Barré syndrome. This report presents the first pediatric CD patient with treatment of ADA, during which VE manifested. Although neurological adverse events associated with ADA are infrequent in pediatrics, vigilant monitoring for neurological symptoms, particularly for infections, remains critical.
Liang Z, Yang Q, Pan G, Yang X, Liu B, Gan W, Yang R, Hao H, Li S, Cai Y
Microbiome & Immunology (22 papers)
Fecal microbiota transplantation mitigates cardiac remodeling and functional impairment in mice with chronic colitis. American journal of physiology. Gastrointestinal and liver physiology | 2026-03-28
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the intestines accompanied by profound extra-intestinal manifestations. Although IBD shows a clear clinical association with cardiovascular derangements, whether and how chronic colitis impairs heart function remains unclear. To address this gap, we investigated the impact of chronic colitis on cardiac performance and the cardiac transcriptome using two mouse models: DSS-treated and Il10-/- mice. Heart function was assessed by echocardiography and molecular characterization was performed using RNA-sequencing, RT-qPCR, and Western blot. Both models exhibited significant functional cardiac impairment, characterized by reduced ejection fraction and fractional shortening along with histologically evident increase in collagen deposition, inflammation, and myofibril reorganization. Molecular analyses revealed a pro-fibrotic cardiac. RNA-sequencing unveiled a shared upregulation of eicosanoid-associated and inflammatory genes (Cyp2e1, Map3k6, Pck1, Cfd) across both models, alongside model-specific alterations in pathways governing cAMP and cGMP signaling, arachidonic and linoleic acid metabolism, and immune cell responses. DSS colitis caused differential regulation of 232 cardiac genes, while Il10-/- colitis yielded 105 dysregulated genes. Notably, reconstitution of a healthy balance of gut microbiota by therapeutic fecal microbiota transplantation (FMT), validated using qPCR, successfully rescued heart function and mitigated fibrosis in both models. However, Il10-/- mice demonstrated relatively less cardiac recovery following FMT, highlighting IL-10’s cardioprotective and anti-inflammatory contribution. Collectively, these findings provide evidence that chronic colitis impairs heart function, offer novel insights into colitis-induced cardiac remodeling, and suggest that FMT mitigates cardiac dysfunction by correcting gut dysbiosis, attenuating systemic inflammation, and re-establishing homeostasis along the gut-heart axis.
Zhong XS, Lopez KM, Liu M, Xiao Y, Ou R, Kochkarian T, Powell DW, Fujise K, Li Q
Advanced engineering of microbiome-related therapeutics for targeted treatment of inflammatory bowel diseases.Review Journal of controlled release : official journal of the Controlled Release Society | 2026-03-27
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the intestine arising from complex interactions among genetic and environmental factors, intestinal barrier dysfunction, immune dysregulation, and gut microbiota dysbiosis. Current therapies for IBD-including anti-inflammatory agents, immunosuppressants, and targeted biologics-remain challenging, as they often cause long-term adverse effects and fail to address the underlying pathological mechanisms. Given these challenges, nano- and bioengineering of microbiome-related therapeutics-including microbial-derived metabolites, probiotics, and prebiotic natural products-has emerged as a promising strategy, offering high biocompatibility and the ability to modulate key disease drivers such as immune responses, barrier restoration, redox balance, and microbiota composition. In this review, we examine the major pathological features of IBD and present engineered microbiome-related platforms designed to overcome the limitations of conventional compounds-such as poor solubility, low bioavailability, rapid degradation or absorption, low probiotic viability, and insufficient accumulation at target sites-while highlighting their therapeutic efficacy in IBD management. Finally, we outline future directions for developing these advanced delivery systems toward more effective and potentially disease-modifying treatments.
Kim YJ, Park N, Cheng X, Lee Y
Role of itaconate in intestinal disease (Review).Systematic review International journal of molecular medicine | 2026-03-27
Itaconate (ITA) is a metabolite produced by immune cells such as macrophages during inflammation or infection. ITA exhibits potent immunomodulatory functions, antioxidant effects and antibacterial properties. The present study aimed to provide a systematic review of the synthesis and metabolic regulatory mechanisms of ITA and its key roles in intestinal diseases. ITA affects inflammatory bowel disease (IBD), colorectal cancer (CRC), intestinal infection and other gut disorders via the regulation of signalling pathways, including the nucleotide‑binding oligomerization domain‑like receptor protein 3 inflammasome, NF‑κB and Nrf2 pathways. ITA also modulates the composition of the gut microbiota and enhances intestinal barrier function. The present study also aimed to summarize the therapeutic potential of ITA derivatives, providing a theoretical basis for the development of novel treatment strategies for intestinal disease.
Li X, Liu Q, Li J, Zhang L, Yao S, Tang L, Yang B, Wang Y, Wen G, An J
A Comprehensive Review of IL-10 and IL-10 Receptor Deficiencies: From Basic Science to Clinical Bedside.Review Clinical reviews in allergy & immunology | 2026-03-26
Interleukin 10 (IL-10) is a potent anti-inflammatory cytokine. IL-10 receptor (IL-10R) consists of two chains of ligand-binding IL-10RA and two subunits of IL-10RB. IL-10 and IL-10R play important role in maintaining immune homeostasis in the gastrointestinal tract. Mutations in the IL10, IL10R cause spontaneous colitis in mice model and very early onset inflammatory bowel disease (VEOIBD) in human. Patients who have disease onset before 6 years of age are defined as VEOIBD. IL10 and IL10 receptor defect are classified as one type of monogenic inborn errors of immunity (IEI). IL-10 signalling defects demonstrate a Mendelian inheritance pattern with complete penetrance of intestinal inflammation. Patients develop symptoms during infancy and have more severe phenotype than polygenic inflammatory bowel disease (IBD). Here, we review the recent advances in the genetic mechanism, population dynamics and innate and adaptive immune dysregulation and interactions of gut microbiota regarding IL-10 signalling defects. The understanding of the pathogenesis has informed therapeutic strategies including haematopoietic stem cell transplant and novel biologics such as interleukin 1 receptor antagonist. Optimised transplant regimen and decreased risk of graft versus host disease with gut immunomodulation with vedolizumab might be used to improve transplant outcomes. More recently, gene therapy and gene editing have become treatment options for a range of IEIs, however evidence for IL-10 signalling defects is limited to in vitro and in vivo models. Beyond the Mendelian disorders, IL-10 signalling and neutralizing autoantibodies against IL-10 is relevant to the pathogenesis of polygenic IBD.
Xiao J, Ye Z, Huang Y
Multi-omics reveal vitamin D regulation of immune-gut microbiome interactions and tolerogenic pathways in inflammatory bowel disease. Cell reports. Medicine | 2026-03-26
Loss of immune tolerance to the gut microbiome plays a pathogenic role in inflammatory bowel disease (IBD). How dietary factors alter host immune-gut microbiome interactions in IBD is unclear. Here, we apply multi-omics (immunoglobulin A or G and 16S rRNA sequencing [IgA-seq, IgG-seq], blood single-cell RNA sequencing [scRNA-seq], and immune repertoire sequencing) to investigate the effects of 12 weeks of vitamin D on host immune microbe interactions in patients with IBD. Vitamin D treatment associates with decreased disease activity and inflammatory markers and increased IgA-bound and decreased IgG-bound gut microbiota. Vitamin D alters the profiles of IgA-bound (increased Lachnospiraceae, Blautia) and IgG-bound (decreased Proteobacteria, Enterococcaceae) gut bacteria. Vitamin D increases B cell activating factor (BAFF) signaling between plasmacytoid dendritic cells and B cells, alters BCR and TCR clonotypes that associate with Ig-bound gut microbiota, and increases α4β7+ B and T regulatory cells. Our results demonstrate that vitamin D promotes immune tolerance to gut microbiota in patients with IBD. Clinical trial is registered under NCT04828031.
Gubatan J, Sojwal RS, Ye J, Boye TL, Hoang JN, Fardeen T, Temby M, Rubin SJS, Spencer SP, Kotagiri P
Isoalantolactone Ameliorates Ulcerative Colitis via Gut Microbiota-Mediated Modulation of Intestinal Barrier, T Cell Homeostasis, and Metabolite Reprogramming. European journal of pharmacology | 2026-03-25
Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by immune dysregulation, epithelial barrier dysfunction, and gut microbiota imbalance. This study examined the therapeutic potential of isoalantolactone (IAL), a bioactive sesquiterpene lactone naturally occurring in Inula helenium L., using a dextran sulfate sodium-induced murine colitis model. Treatment with IAL significantly mitigated weight loss, improved the disease activity index, preserved colon length, and alleviated goblet cell depletion. Mechanistically, IAL enhanced intestinal barrier integrity by upregulating tight-junction proteins zonula occludens-1, occludin, and mucin 2 and suppressing proinflammatory cytokines interleukin (IL)-6, tumor necrosis factor-α, and IL-1β. Moreover, IAL rebalanced CD4+/CD8+ T cell ratios in the colon, mesenteric lymph nodes, and spleen. Gut microbiota analysis revealed increased diversity, enrichment of beneficial taxa (Muribaculaceae, Prevotellaceae_UCG-001), and a reduced Firmicutes-to-Bacteroidetes ratio. Metabolomic profiling identified 130 differentially abundant metabolites, including increased levels of anti-inflammatory compounds (e.g., hydroferulic acid) and decreased levels of proinflammatory lipids (e.g., linoleoylcarnitine). Correlation analysis demonstrated an association between gut microbiota and faecal metabolites. In addition, faecal microbiota transplantation confirmed that IAL-modulated microbiota ameliorated colitis, with pseudo-germ-free recipients exhibiting improved barrier function and immune homeostasis. These findings highlight the importance of IAL as a novel therapeutic candidate for UC by modulating host-microbiota interactions; however, clinical validation is warranted.
Lin F, Zhang D, Liu S, Wu B, Wang J, Yan T, Jia Y
A next-generation probiotic strain for gut health: Bacteroides cellulosilyticus LYH2 variant with anti-inflammatory and metabolic advantages. EBioMedicine | 2026-03-25
The rising global incidence of inflammatory bowel disease (IBD) underscores the pressing demand for effective therapeutic approaches. Among promising next-generation probiotics (NGPs), certain Bacteroides species, notably Bacteroides cellulosilyticus, have attracted increasing interests. However, their mechanisms of action remain incompletely elucidated. Six Bacteroides strains were isolated from porcine intestine, among which B. cellulosilyticus LYH2 was selected for detailed functional characterisation. Genomic and metabolic profiling were conducted to evaluate its polysaccharide-degrading capacity, short-chain fatty acid (SCFA) production, and antimicrobial metabolite synthesis. In vitro and in vivo studies assessed its dose-dependent effects on pathogen inhibition, macrophage infection, immune modulation, and metabolic safety. A dextran sulphate sodium (DSS)-induced colitis model (male C57BL/6J mice), along with Ffar3-deficient mice, was employed to investigate anti-inflammatory efficacy and underlying mechanisms. B. cellulosilyticus LYH2 demonstrated broad-spectrum antimicrobial activity, effectively suppressed macrophage infection, and reduced pro-inflammatory gene expression in vitro. Long-term oral administration proved safe in mice and improved metabolic parameters. In DSS-induced colitis, B. cellulosilyticus LYH2 outperformed a reference Bacteroides strain, mesalamine, and Lactobacillus reuteri in mitigating inflammation and restoring colonic goblet cell numbers. Mechanistically, B. cellulosilyticus LYH2 enhanced colonic propionate production, modulated gut microbiota composition, and activated Ffar3 signalling, consequently attenuating M1 macrophage polarisation. Genetic ablation of Ffar3 largely abolished these protective effects. B. cellulosilyticus LYH2 represents a safe and functionally potent NGP that alleviates experimental colitis via propionate-Ffar3 signalling, supporting its therapeutic potential for intestinal inflammatory disorders. This research was supported by grants from National Natural Science Foundation of China (32372900) and Natural Science Foundation of Sichuan Province (2023NSFSC0237).
Lan C, Deng X, Jin S, Li H, Liu Y, Wu A, Liu Y, Zhang Y, He J, Dai Z
Wheat fiber mitigates colitis via non-SCFA microbial metabolite-trained intestinal macrophages. Science advances | 2026-03-25
The advent of highly refined wheat products has reduced fiber consumption, which is associated with increased risk for inflammatory bowel disease (IBD). We found that enriching diets with wheat fiber (WF) protected mice against colitis, especially relative to a low-fiber diet, as assessed by clinical, histopathologic, morphologic, and immunologic parameters. WF’s protection against colitis was independent of short-chain fatty acids (SCFAs) yet associated with preservation of microbiota diversity, including maintenance of Bacteroides thetaiotaomicron (B. theta), which was necessary and sufficient for WF’s colitis protection. B. theta’s presence in gnotobiotic mice resulted in WF-induced fecal metabolites that reprogrammed macrophages toward an M2-like phenotype. Metabolic and phenotypic reprogramming of macrophages ex vivo via WF-induced metabolites, followed by their transplantation into mice, recapitulated WF’s protection against colitis. Thus, microbiota-mediated metabolism of WF promotes macrophages that reduce proneness to intestinal inflammation, suggesting a mechanism by which WF consumption may curb development of IBD.
Kim SG, Ott R, Bretin A, Abo H, Wang Y, Wang Y, Winer S, Winer DA, Reddivari L, Heaver SL
Hydroxypropyl Methylcellulose as a Functional Dietary Fiber Preserves Intestinal Barrier Integrity via NF-κB Modulation Under Inflammatory Conditions. Journal of medicinal food | 2026-03-25
Intestinal epithelial barrier integrity is crucial for maintaining gut homeostasis and preventing luminal inflammation. Disruption of tight junctions (TJs) by pro-inflammatory cytokines such as tumor necrosis factor-α and interferon-γ contributes to barrier dysfunction, a hallmark of disorders like inflammatory bowel disease. In this study, we investigated the protective effects of hydroxypropyl methylcellulose (HPMC), a widely used excipient and dietary fiber, against cytokine-induced epithelial barrier dysfunction in Caco-2 cell monolayers. HPMC treatment preserved transepithelial electrical resistance, reduced paracellular leakage of FITC-dextran, and significantly suppressed the secretion of inflammatory mediators, including interleukin (IL)-8, IL-1β, IL-6, and monocyte chemoattractant protein (MCP)-1. Furthermore, HPMC restored the expression and localization of TJ proteins zonula occludens-1 and occludin and attenuated NF-κB activation by inhibiting IκBα phosphorylation and subsequent nuclear translocation. These findings indicate that HPMC counteracts cytokine-driven epithelial barrier disruption through coordinated anti-inflammatory and barrier-stabilizing actions. Collectively, our results demonstrate that noncytotoxic HPMC (12.5-100 μg/mL) has potential as a safe pharmaceutical excipient and functional dietary fiber capable of supporting intestinal health under inflammatory conditions.
Kim M, Cho CH, Kim S, Oh MJ, Park HY, Choi IW, Lee SH
Gut pathogen Clostridium symbiosum rewires macrophage succinylation to drive enteric neuron loss in inflammatory bowel disease. Cell host & microbe | 2026-03-24
Inflammatory bowel disease (IBD) is a chronic relapsing and remitting disorder in which loss of intrinsic enteric neurons (iENs) has been documented. However, the contribution of gut microbiota to the loss of iENs in IBD remains poorly defined. Here, we identify an IBD-enriched intestinal pathogen, Clostridium symbiosum (C. symbiosum), which exacerbates iEN loss and colitis. Mechanistically, C. symbiosum-derived succinate, emerging as a central mediator, drives macrophage glycolysis via the H3K79succ/HK2 axis, thereby sustaining IL-1β secretion, which, in turn, promotes neuronal-specific NLRP3 inflammasome activation and consequent neuronal loss. We further demonstrated that preventing iEN loss effectively improves outcomes in C. symbiosum-exacerbated colitis. Importantly, we identified phiCS-1, an endolysin from C. symbiosum-specific bacteriophages, which efficiently lyses C. symbiosum and markedly attenuates C. symbiosum-mediated iEN loss and colitis. Together, our study provides insights into the intricate interplay between gut microbiota and immune-neuron crosstalk, offering avenues for targeted therapeutic interventions in IBD.
Zhao Y, Ning L, Yan Y, Ding J, Yu B, Yang P, Shen N, Xuan B, Wang Z, Zhang Y
A Watermelon-Like Micro/Nano Hierarchical Delivery Platform for Ulcerative Colitis by Regulating Redox Homeostasis and Remodeling Gut Microbiota. Advanced healthcare materials | 2026-03-24
Ulcerative colitis (UC) is a refractory inflammatory bowel disease marked by mucosal barrier damage, immune dysregulation, and microbial imbalance. Current treatments are limited by systemic toxicity and inadequate targeting. Drawing inspiration from the “watermelon seed and watermelon” concept, this study employs microfluidic technology to encapsulate chondroitin sulfate (CSU) based nanoparticles (NPs) loaded with the antioxidant quercetin (Qu@CSCP) within hyaluronic acid/calcium alginate (HACM) hydrogel microspheres. This process yields a “watermelon-like” micro/nano hierarchical hydrogel microsphere system (QC@HACM) specifically designed for targeted combination therapy of UC. The HACM shell protects Qu@CSCP from the harsh gastrointestinal (GI) environment and enables targeted accumulation in inflamed colon tissue. Owing to its colon-adhesive properties, QC@HACM enhances the expression of tight junction proteins and reshapes the gut microbiota, enriching beneficial probiotics. Upon localized release, Qu@CSCP NPs activate the Nrf2/HO-1 antioxidant pathway, induce M2 macrophage polarization, and modulate the Bax/Bcl-2 ratio to suppress epithelial apoptosis. This dual mechanism effectively relieves oxidative stress and promotes mucosal healing. The therapeutic efficacy of these microspheres was further validated in a murine model of UC, as evidenced by reduced levels of pro-inflammatory cytokines accompanied by restoration of gut microbiota homeostasis. Consequently, this oral delivery platform represents a promising stepwise therapeutic strategy for comprehensive UC management.
Wang X, Liu X, Zhou G, Miao Y, Zhao X, Cao Y, Wang Z, Deng D
Oral colon targeted curcumin-based nanocomposite inulin hydrogel for alleviating intestinal inflammation and dysbiosis. Journal of nanobiotechnology | 2026-03-24
Scavenging excess reactive oxygen species (ROS) and positively improving intestinal dysbiosis is a promising therapeutic strategy for alleviating inflammatory bowel disease (IBD). However, conventional clinical drugs and probiotic-based adjuvant therapies often fail to achieve satisfactory results due to systemic side effects of drugs, low bioactivity of probiotics, short intestinal retention time, and poor targeting ability. To address these challenges, we developed an antioxidant-functionalized curcumin loaded nanocomposite inulin hydrogel for targeted IBD therapy. In this system, curcumin was encapsulated within chitosan-coated Poly (lactic-co-glycolic acid) PLGA nanoparticles, which not only exhibited excellent ROS-scavenging capacity but also demonstrated the enhanced cellular uptake behavior. In a dextran sulfate sodium induced ulcerative colitis mouse model, the nanocomposite hydrogel significantly prolonged the intestinal retention time of curcumin, thereby suppressing the expression of pro-inflammatory factors, alleviating intestinal inflammation, and promoting the recovery of intestinal barrier and microbial diversity. This study has developed a synergistic therapeutic strategy via combining anti-inflammatory effects with gut microbiota regulation, offering a novel therapeutic approach for the clinical management of colitis.
Fan Q, Kan C, Wang K, Zhu H, Zhang Y, Lu M, Xue S, Han L, Geng Z, Hou W
MEditome: Computational Detection of RNA Edit Sites Using de Novo Assembly in Microbiomes. Journal of computational biology : a journal of computational molecular cell biology | 2026-03-23
RNA editing is a post-transcriptional modification that alters single-nucleotide sites within RNA strands, thus diversifying transcriptomes and proteomes and modulating gene expression. While better characterized in eukaryotes and in a few microbes, the study of RNA editing in entire microbiomes remains unexplored. Recent studies have demonstrated that A-to-I RNA editing contributes to bacterial adaptation and pathogenicity. Previously, we developed MetaEdit, a reference-based computational pipeline to detect RNA edit sites in microbiomes. While MetaEdit successfully identified RNA edit sites in Escherichia coli within the context of the human gut microbiome, including previously reported loci, it relied primarily on aligning reads to reference genomes of target bacteria. This dependence on reference genomes introduced potential biases, as editing can only be identified in reference genomes, while editing in novel microbial strains missing from the reference databases could be overlooked. Even for reference genomes, the search for edit sites is inefficient since it would have to be conducted one reference genome at a time.Here, we introduce MEditome, employing de novo assembly to overcome these limitations. This crucial change enables the detection of RNA edit sites across all microbial organisms in the microbiome, including novel bacterial strains for which comprehensive reference genomes are unavailable. Using sequencing data from the Integrative Human Microbiome Project, MEditome identified 2,295 unique RNA editing sites across diverse bacterial taxa. Several of these overlaps with previously identified edits in E. coli detected by MetaEdit in hok/gef gene family and arginine-associated genes, providing in silico validation of accuracy. We observed taxon-specific editing patterns and gene-level differential editing associated with inflammatory bowel disease, highlighting RNA editing as a potential regulatory mechanism influencing microbial adaptation and host-microbe interactions.
Mehta A, Stebliankin V, Mathee K, Narasimhan G
Autotaxin Induces S1P/S1PR1 Signaling to Affect Th17/Treg Cell Balance and Exacerbate Intestinal Inflammation in Colitis. International journal of molecular sciences | 2026-03-21
Abnormal intestinal mucosal immunity plays a crucial role in ulcerative colitis (UC). Autotaxin (ATX) can promote T cell migration and was reported to have a regulatory effect on Th17 cells, while sphingosine-1-phosphate (S1P) and its receptors (S1PRs) modulate Th17/Treg balance and inflammation, with S1PR modulators approved for UC. ATX can catalyze sphingosylphosphorylcholine (SPC) to produce S1P; however, the relationship between ATX and S1P/S1PRs in UC is unclear. Understanding the role of ATX-S1P/S1PRs in intestinal immunity can provide new treatment strategies for intestinal inflammatory diseases. Both UC patients and DSS-induced colitic mice showed significantly increased levels of ATX and S1P compared with healthy controls. ATX inhibitor PF8380 treatment led to reduced levels of S1P/S1PRs in colitic mice. Consistent with this, the S1PR antagonist etrasimod was able to alleviate ATX-induced intestinal inflammation, as well as partially restore ATX-induced Th17/Treg imbalance in MLNs and the spleen. In HT-29 and Raw246.7 cells, ATX treatment led to enhanced expression of S1P/S1PRs, with S1PR1 being the most significant. Furthermore, S1PR1 mediates the effect of ATX on Th17/Treg cell differentiation and function in vivo. Therefore, ATX affects the differentiation and function of Th17/Treg cells through S1P/S1PR1 signaling, increased ATX expression leading to Th17/Treg cell imbalance, intestinal mucosal immune dysfunction, and exacerbating intestinal inflammation.
Xiao S, Peng K, Li C, Long Y, Yu H, Xia S, Tan Q, Yu Q
Orally delivered, pH-resistant dual coated extracellular vesicles restore intestinal barrier function and suppress colitis. Biomaterials | 2026-03-20
Oral therapy for inflammatory bowel disease (IBD) requires drug formulations that can withstand gastrointestinal stress and achieve localized action at the inflamed mucosa, yet existing extracellular vesicles (EVs)-based or small-molecule approaches often fail due to poor stability and limited colonic delivery. This study aimed to develop a dual-coated oral delivery platform that enhances gastrointestinal stability and targeted drug release. We engineered macrophage-derived EVs sequentially coated with a cationic lipid and sodium alginate (SA) to encapsulate 5-aminosalicylic acid (5-ASA). This stepwise surface charge-switching strategy preserved EV identity, conferred resistance to acids and enzymes, and enabled delayed uncoating at colonic pH. In a gastrointestinal-mimicking Caco-2-THP-1 co-culture model, dual-coated EVs (DCEVs) exhibited enhanced epithelial uptake, transepithelial transport, and macrophage delivery compared to unmodified EVs. In a dextran sodium sulfate (DSS)-induced colitis model, 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) facilitated endosomal escape and SA enabled timed release, resulting in increased colonic exposure, significant recovery of colon length, restoration of intestinal tight junctions, suppression of pro-inflammatory cytokines, and increased IL-10 expression. Collectively, these results demonstrate that a sequential coating strategy can effectively integrate EV-mediated immunomodulation with pharmacologic therapy, providing a pH-stable oral EV platform for localized treatment of IBD.
Cho CW, Roh J, Lee S, Cho HB, Lee J, So G, Na K, Kim HJ, Park KH
Tibetan Fritillaria cirrhosa D. Don Extract Ameliorates DSS-Induced Ulcerative Colitis by Repairing Damage to the Intestinal Mucosal Barrier and Regulating the Gut Microbiota. Nutrients | 2026-03-19
Background/Objectives: Ulcerative Colitis (UC) is a chronic inflammatory disease of the colon that profoundly impacts human health. Conventional pharmacological treatments are associated with serious adverse reactions and toxic side effects. Consequently, the development of natural plant-derived biological agents for UC treatment is an urgent imperative. Methods: Utilising a Dextran Sulfate Sodium (DSS)-induced ulcerative colitis mouse model, with mice receiving low, medium, and high doses of water extract of Tibetan Fritillaria cirrhosa D. Don extract (FCD), alongside a group receiving 5-aminosalicylic acid. The Disease Activity Index (DAI) was calculated, colon length was measured, histological scores were assessed, and histopathological alterations were evaluated. Inflammatory factor were determined by ELISA; mRNA and protein expression in colonic tissue was analysed by RT-qPCR and Western blotting; intestinal barrier-related proteins were examined by immunofluorescence and immunohistochemistry; and gut microbiota composition was assessed by 16S rRNA sequencing. Results: Research has confirmed that FCD alleviates symptoms of DSS-induced colitis in mice, specifically manifested by a slower rate of weight loss, reduced colon shortening, and decreased disease activity index. It has been demonstrated that the process under investigation exerts a beneficial effect on intestinal injury by means of a number of mechanisms. These include increased goblet-cell production, elevated IL-10 levels, and reduced levels of TNF-α, IL-1β, and IL-6. Furthermore, immunofluorescence detection, immunohistochemical analysis, and RT-qPCR results indicate that FCD maintains the integrity of the intestinal mucosal barrier by enhancing the expression of Zonula occludens-1 (ZO-1), occludin, and claudin-1 proteins and their corresponding mRNAs, in addition, FCD can regulate the gut microbiota and promote its diversity. Conclusions: Research indicates that FCD may exert therapeutic effects on ulcerative colitis (UC) by regulating intestinal barrier integrity and modulating the gut microbiota. These findings reinforce the idea that FCD could be used as a natural therapy to improve UC.
Hao Z, Chen X, Peng Q, Wu R, Zhang H, Yin P, Yu X, Wang S
From Macromolecule to Microbe: Identification of Ligilactobacillus salivarius D3-8 as a Key Degrader of Ejiao and a Novel Therapeutic Probiotic for Ulcerative Colitis. Nutrients | 2026-03-17
Background/Objectives: Ejiao, a macromolecular protein complex derived from donkey hide, is a traditional Chinese medicine with clinically demonstrated efficacy against ulcerative colitis (UC). Due to its large molecular size and poor absorbability, its therapeutic effects are presumed to depend on gut microbiota. We hypothesized that specific gut bacteria capable of degrading Ejiao might also mediate its biological functions. Methods: To test this hypothesis, a systematic investigation was conducted by integrating culturomics, proteomics, metabolomics, 16S rRNA gene amplicon high-throughput sequencing, and animal disease models. Results: A total of 134 human gut bacterial strains capable of utilizing Ejiao as a nutrient source were isolated. Among them, Ligilactobacillus salivarius D3-8 exhibited the strongest growth in Ejiao-based medium. Genomic analysis identified 63 protease/peptidase genes, and peptidomic profiling confirmed its degradation activity, which released 50 novel peptides. Notably, administration of L. salivarius D3-8 alone significantly alleviated dextran sodium sulfate (DSS)-induced colitis, concurrently increasing the abundance of beneficial bacterium Dubosiella newyorkensis and elevating the anti-inflammatory metabolite indole-3-carbinol via upregulated tryptophan metabolism. Conclusions: Our findings identify L. salivarius D3-8 as both a dedicated Ejiao-degrader and a protective probiotic against colitis. This work provides direct evidence that gut bacteria can utilize Ejiao and proposes a potential novel mechanistic framework in which the biological effects of Ejiao may be mediated through its interaction with specific, functionally potent degraders such as L. salivarius D3-8.
Dai W, Ma M, Feng Q, Duan X, Zhang Y, Zhou X, Liu H, Shang Q
Anti-Inflammatory Potential of Novel Tethered Agonists of the Adhesion G Protein-Coupled Receptor F5. International journal of molecular sciences | 2026-03-13
The adhesion G protein-coupled receptor F5 (ADGRF5) has been implicated in modulating immune responses in cancer; however, its role in inflammatory bowel diseases (IBDs), particularly colitis, remains largely unexplored. In this study, we aimed to design and characterize novel peptide agonists derived from the ADGRF5 Stachel sequence, as well as to evaluate their therapeutic potential in preclinical colitis models. In silico analysis and single amino acid substitutions within the ADGRF5 tethered agonist sequence, combined with functional assays in ADGRF5-overexpressing cells, including calcium mobilization and inositol phosphate production, were employed to assess the activity of novel ADGRF5 agonists. Western blot technique and murine model of colitis were used to evaluate downstream signaling pathways and immunomodulatory effects of ADGRF5 ligands. We identified a series of peptides exhibiting significantly enhanced ADGRF5 agonist activity, achieving up to a 6-fold increase in potency over the wild-type version. We identified critical substitutions within the Stachel sequence, namely S11N and D13S, as essential for improving agonistic activity. Finally, using these novel ADGRF5 agonists, we demonstrated their potent anti-inflammatory effects in vivo, showing that ADGRF5 activation ameliorates experimental colitis, as evidenced by reduced macroscopic damage scores and improved colon architecture. These findings establish ADGRF5 as a potential therapeutic target for colitis and highlight the promise of Stachel-derived peptide agonists for the development of novel anti-inflammatory therapies.
Wnorowski A, Pietrzak-Mitura D, Mudgal A, Scrofani L, Strachowska M, Draczkowski P, Jóźwiak K, Fichna J, Jacenik D
Recent Advances in Exploring Casein Peptide Regulation of Inflammatory Bowel Disease from an Intestinal Barrier Perspective: Correlations, Mechanisms, Challenges and Solutions.Review Foods (Basel, Switzerland) | 2026-03-11
Inflammatory bowel disease (IBD) is characterized by chronic and intermittent symptoms, exerting a profound impact on overall health. Although drug therapy and biological agents are primary treatment approaches for IBD, the side effects can affect human health. Thus, it is an urgent need to explore new approaches to counteract the harm caused by IBD. Owing to their natural origin and excellent biosafety, casein peptides are a promising candidate treatment for IBD. This review systematically outlines the structural basis of the intestinal barrier and elucidates the pivotal role of barrier dysfunction in IBD pathogenesis. We further elaborate on the multi-faceted therapeutic mechanisms of casein peptides in IBD, including intestinal barrier repair, immune homeostasis modulation, inflammatory response suppression, and other such pathways. Moreover, we analyze the key challenges of intestinal-barrier-targeted casein peptide therapies in current research and translational practice, and propose future perspectives for overcoming these limitations, thus providing a reference for potential new preventive and therapeutic approaches to IBD.
Dong T, Ye J, Zhang J, Song W, Xia S, Li X, Liu M, Pan D, Wu Z, Tu M
Modulation of gut microbiota and metabolic profiles by Astragaloside IV in a chronic enteritis model. Frontiers in cellular and infection microbiology | 2026-03-11
Chronic intestinal inflammatory diseases like ulcerative colitis severely impact millions globally. Current treatments using drugs manage inflammation short-term but have significant side effects and don’t address underlying issues like mucosal barrier repair. New treatments are needed, and Chinese herbal medicine is gaining attention for its low cost and side effects. This study used a DSS-induced chronic enteritis animal model and treated it with Astragaloside IV(AS-IV), a traditional Chinese medicine. 16S sequencing and LC-MS analysis showed that AS-IV significantly reduces DSS-induced inflammation. This encompasses an enhancement in body weight, a reduction in the bleeding index, diarrhea index, and disease activity index (DAI). Furthermore, AS-IV has the capacity to modulate gut microbiota diversity, augment the abundance of beneficial bacteria, diminish the prevalence of harmful bacteria, and mitigate disease progression through alterations in metabolic profiles. Integrated omics analysis has revealed that AS-IV can attenuate disease progression by modulating the biosynthesis of primary bile acids. In summary, this study showed that AS-IV significantly protects against chronic enteritis, as demonstrated by a DSS-induced colitis model. It explored the mechanisms involving gut microbiota and its metabolites, highlighting a new understanding of AS-IV’s pharmacological effects and the crucial role of gut microbiota in enhancing the anti-inflammatory properties of traditional Chinese medicine monomers.
Liu JX, Xu YH, Li SD, Zhang YF, Yang JC, He RL
Host-gut microbiota interactions in health and disease: mechanisms and intervention strategies.Review Frontiers in microbiology | 2026-03-10
The mammalian gut microbiota is a complex and dynamic “microbial organ” that interacts with its host. The gut microbiota contains a vast gene pool and metabolic capacity, producing key metabolites such as short-chain fatty acids (SCFAs), bile acids, vitamins, and other compounds. These metabolites regulate core physiological functions like energy metabolism, immune homeostasis, and neural behavior via the gut-brain axis (GBA), immune signaling networks, and other pathways. This review explores the bidirectional regulatory role of the gut microbiota. The gut microbiota influences the host’s metabolism and immune functions through its metabolites and structural components, while the host’s physiological state, internal environment, and lifestyle can alter the microbiota’s composition and function, creating a complex feedback network. Furthermore, the main mechanisms of dysbiosis in diseases are also explored. Dysregulation of the gut microbiota can damage the intestinal mucosal barrier, induce chronic inflammation, disrupt metabolic and immune signaling, and contribute to diseases such as type 2 diabetes, non-alcoholic fatty liver disease, inflammatory bowel disease, rheumatoid arthritis, and neurodegenerative disorders. Microbiota-based interventions, such as probiotics, prebiotics, and fecal microbiota transplantation (FMT), can be promising in disease management, but their clinical applications face challenges, including individual genetic backgrounds, lifestyles, and environmental factors, as well as difficulties in achieving long-term colonization of specific strains. Future research needs to uncover precise causal mechanisms in host-microbe interactions, as well as develop individualized microbiota intervention strategies to provide new theoretical bases and practical tools for the prevention, diagnosis, and treatment of major diseases.
Han Y, Wang Z, Xie J, Yang G, Su M, Wang S, Yang M, Yu H, Li M, Wang L
STEAP4 Modulates Intestinal Barrier Dysfunction and Inflammatory Signaling Pathways in Ulcerative Colitis. Shock (Augusta, Ga.) | 2026-03-09
Ulcerative colitis (UC) is characterized by intestinal barrier dysfunction and chronic inflammation, yet its underlying mechanisms remain incompletely understood. This study investigates the role of Six-transmembrane epithelial antigen of the prostate 4 (STEAP4), a metalloreductase linked to redox regulation, in UC pathogenesis. Using clinical samples from IBD patients, a dextran sulfate sodium (DSS)-induced murine colitis model, and lipopolysaccharide (LPS)-treated intestinal epithelial cells (NCM460 and HT-29), we demonstrated that STEAP4 expression was significantly upregulated in inflamed mucosa across human, murine, and in vitro models. H&E staining, and Western blot analyses verified the successful modeling of DSS-induced colitis mice. STEAP4 knockdown via siRNA restored tight junction protein claudin-1 expression (p < 0.05; n=3), increased TEER value (p < 0.001; n=3), decreased the permeability of FITC-D (p < 0.01, p < 0.001; n=3) and suppressed LPS-induced pro-inflammatory cytokines (TNF-α, IL-6) (p < 0.05; n=3) by attenuating NF-κB phosphorylation (p65, IκBα) (p < 0.05, p < 0.01, p < 0.001; n=3). These findings position STEAP4 as a critical regulator of mucosal inflammation, bridging redox homeostasis, epithelial barrier function, and NF-κB-driven immune responses. Our study highlights STEAP4 as a potential therapeutic target for restoring intestinal homeostasis in UC, warranting further exploration of its molecular interactions and translational applications.
Xu S, Chen P, Shi X, Li M, Liu Z, Lu C, Sheng Y
Pathogenesis & Basic Science (20 papers)
Irgm1 Restrains CD8+ T Cell Cytokine Production and Apoptosis via Cell-Extrinsic Regulation of Type I Interferon Signaling. European journal of immunology | 2026-04
Immunity-related GTPases (IRGs) are a family of proteins that maintain cellular homeostasis by promoting autophagy and mitophagy. Mutations in human IRGM and genetic deletion of mouse Irgm1 have been linked to increased severity of inflammatory bowel disease, cancer, sepsis, and various infections. While IRGM/Irgm1 are known cell-intrinsic regulators of inflammation, their roles in T cell function remain poorly understood. We previously demonstrated that Irgm1 deficiency leads to increased production of proinflammatory mediators, including Granzyme B and interferon-γ, and increased apoptosis in CD8+ T cells. Here, we show that Irgm1 deficiency also alters Granzyme B production and impairs virus-specific CD8+ T cell responses during lymphocytic choriomeningitis virus (LCMV) infection. Using T cell-specific Irgm1 knockout mice and adoptive transfer experiments, we unexpectedly found that Irgm1 regulates CD8+ T cell responses through a cell-extrinsic mechanism. Transcriptomic and genetic analyses identified type I interferons (IFNs) as key mediators of this effect. These findings reveal a previously unrecognized, cell-extrinsic role for Irgm1 in regulating CD8+ T cell survival and function by modulating the inflammatory environment. Our results suggest that IRGM/Irgm1 acts as a critical immune rheostat, restraining pathological inflammation and modulating T cell responses in infection and autoimmunity.
Molloy CT, Alwarawrah Y, Cohen JA, Fee BE, Whitmire JK, Taylor GA, MacIver NJ
IL-22 induces Paneth cell metaplasia in the colonic epithelium of ulcerative colitis, promoting wound healing via REG3A. Nature communications | 2026-03-28
Paneth cell metaplasia (PCM) is a phenomenon in which Paneth cells, typically found in the small intestine, appear in the colonic epithelium of patients with ulcerative colitis (UC). Our study demonstrates that the PCM occurrence correlates with disease duration and active inflammation. Furthermore, we identified IL-22, an inflammation-associated cytokine, as a key regulator that promotes PCM formation in the colonic epithelium through suppression of Notch signaling and induces REG3A expression within metaplastic niches. In vitro, we show that Reg3a directly enhances cell proliferation and promotes wound healing using mouse colonic organoids. In vivo, Reg3aΔIEC mice in both acute and chronic DSS-induced colitis models exhibit delayed wound healing. Additionally, studies conducted with patient-derived human colonic organoids revealed that REG3A administration stimulates cell proliferation and accelerates wound healing. Together, these findings support a protective role of PCM-associated REG3A in the colonic epithelium of patients with UC.
Muto T, Ito G, Katsuda H, Hiraguri Y, Fujii S, Yamamoto K, Bernardes JP, Hinrichsen F, Uchida H, Nemoto Y
Modulation of mTOR, NLRP3, and Nrf2/HO-1 signaling by atorvastatin and nitazoxanide in experimental ulcerative colitis. Naunyn-Schmiedeberg’s archives of pharmacology | 2026-03-27
The exact etiology of ulcerative colitis (UC) remains incompletely understood. However, substantial evidence implicates multiple signaling pathways in its pathogenesis, including interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3), wingless/Int1 (Wnt), heme oxygenase-1 (HO-1), nuclear factor erythroid 2-related factor 2 (Nrf2), adenosine monophosphate-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), and NLR family pyrin domain-containing 3 (NLRP3). Atorvastatin and nitazoxanide have demonstrated anti-inflammatory, antioxidant, and immunomodulatory properties that may target these signaling pathways. The aim of this study was to investigate the coloprotective effects of atorvastatin and nitazoxanide in an experimental model of UC. Colitis was induced by intracolonic administration of acetic acid (AA) in rats. A total of 32 rats were randomly assigned to four groups (n = 8 each): normal control, colitis, atorvastatin-treated, and nitazoxanide-treated groups. Disease severity was assessed via colon length, weight, disease activity index, and histopathological evaluation. Tissue levels of SIRT1, mTOR, HO-1, Nrf2, STAT3, AMPK, and Dickkopf-related protein 1 (DKK1) were measured, along with colonic gene expression of NLRP3, Wnt, IL-6, TNF-α, and DKK1. Additionally, TNF-α and IL-6 protein expressions were assessed by immunohistochemistry. Intracolonic AA administration caused significant biochemical, inflammatory, and structural damage to the colon. Both atorvastatin and nitazoxanide significantly attenuated colitis, as evidenced by reduced disease activity scores, histological improvement, and decreased expression of colonic mTOR, NLRP3, DKK1, IL-6, TNF-α, and STAT3. Conversely, both agents upregulated HO-1, Nrf2, SIRT1, Wnt, and AMPK levels. Histologically, treated groups exhibited partial restoration of normal mucosal architecture, with fewer irregular crypts and reduced lymphoplasmacytic infiltration. Atorvastatin and nitazoxanide ameliorated experimental colitis through modulation of inflammatory and oxidative stress pathways.
AlRasheed HA, Abdallah MS, Mosalam EM, Bahaa MM, Salahuddin MM, Hamouda AO, Alrubia S, Alsegiani AS, El-Khateeb E, Elmahdy MK
A novel enema formulation containing cannabidiol and sodium propionate for ulcerative colitis: preclinical assessment in a murine model. Journal of cannabis research | 2026-03-24
Abstract not available.
Naftali T, Prutchi Sagiv S
Immune dysregulation, apoptosis impairment, and enhanced seroreactivity to Anisakis simplex in Crohn’s disease: interplay of IL-7/IL-7R signalling and CD132 deficiencyFIRST REVIEW ROUND - REVIEWERS COMMENTSREVIEWERS COMMENTSREVIEWERS COMMENTS. Memorias do Instituto Oswaldo Cruz | 2026-03-23
In previous studies, we identified a deficiency of γδ T cells and an increased prevalence of anti-Anisakis simplex antibodies in patients with Crohn’s disease (CD). Additionally, decreased gene expression of the interleukin 2 (IL-2) receptor γ subunit (CD132) was observed in tissues from CD patients. To analyse the gene expression of IL-7 and its receptors in tissues from CD patients and to explore its relationship with anti-A. simplex antibodies. 52 patients diagnosed with CD were compared with a control group of 52 healthy individuals. Peripheral blood samples were analysed to assess levels of anti-A. simplex antibodies and IL-7. In addition, intestinal tissue samples from 20 subjects in each group were examined to evaluate IL-7 gene expression, IL-7 protein levels, the IL-2 receptor γ subunit (CD132), the IL-7 receptor α subunit (CD127), and caspase-3 expression. Anti-A. simplex antibody levels were elevated in patients with CD. Caspase-3 expression was significantly reduced in the tissues of CD patients with anti-A. simplex IgA, and this reduction extended to IgG and IgE in healthy individuals. A negative correlation was observed between caspase-3 levels and serum anti-A. simplex IgA, as well as IL-7 levels in the tissues of CD patients. In healthy subjects, tissue IL-7 levels were lower in those positive for anti-A. simplex IgA, while serum IL-7 levels were higher in individuals positive for anti-A. simplex IgG. This study revealed the interplay between IL-7 signalling, γδ T cell deficiency, and immune responses to A. simplex in CD. Our findings underscored a cause-effect relationship between CD132 deficiency, γδ T cell depletion, and defective mucosal immunity, which may drive both CD inflammation and susceptibility to parasitic infections like A. simplex.
Cuéllar C, Hurtado-Marcos C, Valdivieso E, Vaccaro L, González-Fernández J, Jiménez AI, Pérez-Griera J, Benlloch S, Amorós C, Gil-Borrás R
A Combined Colon Organoid-Sensory Neuron Model Reveals Epithelial Contribution to Moringin Efficacy Against Painful Inflammatory Bowel Disease. Phytotherapy research : PTR | 2026-03-23
Visceral pain is a major symptom of inflammatory bowel diseases (IBDs), requiring effective treatment strategies. Gut epithelium, beyond maintaining barrier integrity and microbiota homeostasis, modulates neurosensorial circuitries, influencing visceral sensitivity. Moringa oleifera constituents show beneficial properties that may counteract inflammation-induced epithelial dysfunction and visceral hypersensitivity. Among these, we investigated moringin (MOR), the isothiocyanate derived from the myrosinase (MYR)-mediated hydrolysis of glucomoringin (GMG). A three-stage experimental strategy was applied. First, murine colon organoids were exposed to a pro-inflammatory cytokine cocktail (CKs; TNF-α, IL-1β, IL-6; 10 ng mL-1, 6 h) to model epithelial inflammatory stress and treated with MOR (2-30 μM). Second, epithelial-neuronal communication was assessed by exposing primary dorsal root ganglion (DRG) neurons to conditioned media from inflamed organoids, with (CMCKs + MOR 30 μM) or without (CMCKs) MOR treatment. Third, the therapeutic relevance of these findings was validated in vivo using a dextran sulfate sodium (DSS)-induced colitis model, in which mice received oral administration of MYR-bioactivated GMG (GMG + MYR) at different doses (30-100 mg kg-1), followed by behavioral and histological assessments. CKs-treated organoids showed cytotoxicity, increased superoxide dismutase activity, and upregulation of Ccl2, Ccnd1, Mki67, and Pyy. MOR 30 μM co-treatment normalized oxidative stress and gene expression, although cytotoxicity remained unaffected. CMCKs increased c-Fos and CGRP expression in DRG neurons, while CMCKs + MOR 30 μM prevented this response, indicating MOR modulation of epithelial inflammation-driven neuronal activation. In DSS-treated mice, oral GMG (30-100 mg kg-1) + MYR dose-dependently reduced visceral hypersensitivity, pain-associated behavioral alterations, and colonic damage. Overall, MOR/GMG + MYR showed gut-protective and analgesic effects under intestinal inflammation. Intestinal organoids effectively model inflammation and therapeutic responses, potentially reducing animal use in IBD research.
Margiotta F, Lucarini E, Toti A, Cataldi MG, Ciampi C, De Nicola GR, Di Cesare Mannelli L, Ghelardini C
Biotransformation of Maclekarpine E in Rats: CYP2C19-Mediated Metabolism, Fecal Enrichment, and Network Pharmacology-Based Anti-Ulcerative Colitis Prediction. Current issues in molecular biology | 2026-03-23
Maclekarpine E is a minor alkaloid from Macleaya species with reported in vitro anti-inflammatory activity, but its in vivo metabolism remains unexplored. This study investigated the metabolic fate of maclekarpine E in rats and evaluated the potential pharmacological relevance of its metabolites. Maclekarpine E was orally administered to male Sprague-Dawley rats (250 mg/kg). Plasma, urine and feces were collected and analyzed by UPLC-Q-TOF-MS/MS. CYP phenotyping was performed using recombinant human enzymes. Molecular docking against ABCG2 and ABCC2 was conducted to assess potential interactions of all fecal compounds with these efflux transporters. Network pharmacology was employed to predict potential anti-ulcerative colitis-related targets of the metabolites, generating hypotheses for future experimental validation. Nineteen phase I metabolites were identified. Biotransformations included ring-opening, demethylation and oxidation. All 19 metabolites were detected in feces, nine in plasma and two in urine. No phase II conjugates were observed. CYP2C19 was the only significantly active isoform under the tested conditions, mediating approximately 16.5% substrate depletion (p < 0.05). All 20 fecal compounds bound ABCG2 (ΔG < -5.0 kcal/mol); 19 bound ABCC2. Network pharmacology yielded 57 overlapping targets with ulcerative colitis, enriched in PI3K-Akt and MAPK pathways. This study provides the first comprehensive metabolic profile of maclekarpine E in rats. The compound undergoes CYP2C19-mediated oxidation and is predominantly excreted into feces. Its fecal metabolites are potential ABCG2/ABCC2 substrates and may target UC-associated pathways based on network pharmacology predictions, warranting further experimental validation.
Yang Y, Wang L, Xue J, Dong Z, Cheng P
Correction: Modulation of inflammatory and oxidative stress pathways by ethanolic extract of Suaeda fruticosa Forssk. Ex J.F.Gmel in animal models of ulcerative colitis. Inflammopharmacology | 2026-03-23
Abstract not available.
Liu J, Mustafa A, Fiaz M, Zubair HM, Maqbool T, Rehman AU, Asif M, Yang J
STING activation promotes intestinal mucin secretion in IBD. Biochimica et biophysica acta. Molecular basis of disease | 2026-03-22
Goblet cells produce mucus protecting the intestinal epithelium. Depleted goblet cells and a disrupted mucus layer are observed in inflammatory bowel diseases (IBD). Remarkably, both deficiency and overactivation of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway lead to goblet cell depletion in mice. Here, we analyzed the role of cGAS-STING in goblet cell mucus regulation in IBD patients and human crypt-derived colonic organoids (HCO). MUC and cGAS-STING pathway gene expression was analyzed in inflamed and non-inflamed mucosa (n = 821) of IBD patients and non-IBD controls, complemented by MUC2 and STING pathway (immune)histochemistry. HCO were exposed to the STING agonist diABZI and antagonist H151. STING pathway activation and MUC2 regulation were assessed by qPCR, Western blotting and immunofluorescence microscopy. Gene expression of many mucins, including MUC2, and cGAS-STING pathway factors were enhanced in inflamed ileum and colon compared to non-inflamed mucosa. Histologically-recognizable (mucus-filled) goblet cells were reduced in inflamed IBD mucosa, yet de novo-synthesized immature MUC2 was readily detected alongside elevated levels of activated/phosphorylated STING. DiABZI dose-dependently enhanced p-STING in HCO, without affecting MUC2 gene expression. Mature MUC2 accumulated in the lumen of diABZI-treated HCO reducing the number of MUC2-filled goblet cells, while immature MUC2 remained detectable, marking the abundant presence of goblet cells lacking mature MUC2. In contrast, H151 treatment did not reduce the number of mucus-filled goblet cells in HCO. STING activation contributes to enhanced mucus release in inflamed IBD epithelium, providing a mechanistic explanation for the apparent histological depletion of goblet cells.
Yang Y, Blokzijl T, da Costa de Pina AM, de Jong S, Weersma RK, Dijkstra G, Faber KN
Autotaxin-Scavenging Nanoliposomes for Prolonged Colon Retention and Autophagy-Mediated Mucosal Immune Restoration in Colitis. Biomaterials research | 2026-03-19
Inflammatory bowel disease (IBD) is an immune-mediated disorder driven by overactivation of autotaxin (ATX), which elevates lysophosphatidic acid (LPA) signaling and suppresses autophagy, exacerbating intestinal inflammation. Given the pivotal role of autophagy in maintaining intestinal homeostasis, inhibiting ATX offers a dual therapeutic mechanism by both restoring autophagic activity and attenuating LPA-mediated inflammatory responses. Current treatments are hindered by nonspecific immunosuppression and frequent systemic side effects, underscoring the need for targeted, multifunctional therapeutic strategies. Here, we present a dual-functional nanotherapeutic platform, ATX-scavenging liposomes loaded with rapamycin (AS-Lipo@R), engineered for the oral treatment of acute colitis. Our proposed formulation incorporates BMP-22, a lipid ATX inhibitor that simultaneously functions as a structural building block of the liposomal membrane. Rapamycin, an autophagy activator, is encapsulated within the bilayer of liposomes. We confirmed that AS-Lipo@R exhibits strong binding affinity to extracellular ATX and mediates its lysosomal degradation upon cellular internalization, thereby demonstrating its ATX-scavenging property. In vitro, AS-Lipo@R inhibited inflammatory macrophage activation, promoted M2 macrophage polarization, and substantially restored autophagic activity in LPS/IFN-γ-stimulated macrophages. In vivo, oral administration of AS-Lipo@R led to preferential accumulation in ATX-overexpressing inflamed colonic tissue, resulting in reduced pro-inflammatory cytokine production, recovered autophagy, and enhanced intestinal barrier integrity in colitis mice. These findings highlight AS-Lipo@R as a synergistic and targeted nanomedicine that simultaneously modulates ATX and autophagy pathways, offering novel insights into immunomodulatory strategies for IBD treatment.
Jeon SW, Kwon J, Ko HG, Yoon JS, Sohn HS, Yoon JK, Bhang SH, Kang MH, Kim HY
Silicon-based agent mitigates fatty liver formation in a CDAHFD60-induced MASH mouse model by enhancing hepatic function. Biochemistry and biophysics reports | 2026-03-18
Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disorder marked by hepatic inflammation and injury caused by excessive fat accumulation unrelated to alcohol consumption. Its global.preva lence is increasing with obesity and metabolic syndrome and even at the simple steatosis stage, the risks of atherosclerosis, myocardial infarction, and stroke are elevated. Persistent MASH can advance to cirrhosis and hepatocellular carcinoma, underscoring the urgent need for effective therapies. Because oxidative stress drives MASH progression, antioxidants are considered promising interventions. Silicon (Si)-based agent acts as antioxidants that continuously generate molecular hydrogen through reaction with water, a known reactive oxygen species scavenger. Oral Si-based agent has shown benefits in oxidative stress-related disorders, including ulcerative colitis, Parkinson’s disease, and intestinal ischemia-reperfusion injury. Here, we investigated whether Si-based agent exerts therapeutic effects on MASH using a choline-deficient, l-amino acid-defined, high-fat diet (CDAHFD60)-induced MASH mouse model. The Si-based agent was mixed at 2.5% into the CDAHFD60 and administered to mice for 12 weeks. Although no apparent macroscopic differences in fatty liver were observed, Si-based agent-treatment reduced hepatic lipid droplet accumulation by preventing MASH-associated bile dysfunction. Additionally, although the MASH models exhibited hypolipidemia and weight loss, Si-based agent-treatment alleviated hypolipidemia and suppressed weight loss. Furthermore, the Si-based agent attenuated systemic oxidative stress in the MASH mouse model. Overall, Si-based agent improved hepatic and systemic lipid metabolism, exerted systemic antioxidant effects, highlighting its therapeutic potential for MASH.
Koyama Y, Kobayashi Y, Hirota I, Kobayashi H, Shimada S
Fruit and Vegetable Supplemented-Diet Ameliorates Dextran Sodium Sulfate (DSS)-Induced Colitis by Modulating Host Transcriptome and Gut Metagenome Response. Nutrients | 2026-03-16
Background/Objectives: Dietary intake of fruits and vegetables (FVs) has been inversely associated with a lower risk of ulcerative colitis. Using a pig model, we evaluated the effect of FV supplementation on dextran sulfate sodium (DSS)-induced colitis. Methods: Six-week-old pigs were fed a grower diet (negative control), grower diet + 4% DSS (positive control), half-FV diet + DSS, or full-FV diet + DSS. FV levels matched half or full daily recommendations from the Dietary Guidelines for Americans (DGA). Clinical signs were monitored; proximal colon contents (PCs) and mucosa (PCM) were analyzed for metagenome, transcriptome and histopathology. Results: Full-FV pigs showed no diarrhea, less fecal occult blood (FOB), crypt hyperplasia, but no changes in gene expression or microbiome diversity (p < 0.05). Half-FV pigs had increased FOB, differentially expressed genes (DEGs) linked to tissue remodeling, crypt/goblet cell hyperplasia and two cases of diarrhea (p < 0.05). DSS controls showed reduced immune-related DEGs, altered microbiome, PCM erosion, FOB, and persistent diarrhea in one pig (p < 0.05). Conclusions: A three-week full-FV diet conferred protection against DSS-induced colitis, with a dose-dependent protection of intestinal tissue and gut metagenome under inflammatory challenge.
Solano-Aguilar G, Lakshman S, Chen C, Beshah E, Molokin A, Vinyard B, Dawson HD, Santin-Duran M, Bruna G, Smith A
A comparative study of dextran sodium sulfate-induced and spleen-kidney syndrome-based ulcerative colitis models. Biochemistry and biophysics reports | 2026-03-16
Accurate animal models are essential for elucidating the pathogenesis of ulcerative colitis (UC). The widely used dextran sodium sulfate-induced UC (DSS-UC) model inadequately reflects the refractory nature of human UC. This study compared the traditional Chinese medicine (TCM)-based SKYD-UC model with the DSS-UC model to identify a more representative model. Network pharmacology was used to analyze the fundamental TCM syndrome of UC and to identify differential targets and pathways between DSS-UC and SKYD-UC. Both UC animal models were subsequently established, and body weight, organ indices, disease activity index (DAI) scores, colon length, mucosal damage, and serum biomarkers (IL-6, TNF-α, MPO, GSH-Px, GAS, and MTL) were evaluated. Among the seven TCM syndromes, SKYD-UC presented the greatest number of targets and pathways, highlighting its fundamental importance. Specifically, 464 and 703 unique targets were identified for DSS-UC and SKYD-UC, respectively. DSS-UC unique targets were predominantly associated with inflammation, immune regulation, and cellular signaling. In contrast, SKYD-UC targets encompass a broader range of biological processes, including mitochondrial dysfunction, extracellular matrix remodeling, and pathways related to systemic UC complications. These findings were validated in animal experiments. Compared with the DSS-UC model, the SKYD-UC model demonstrated more severe damage, including pronounced spleen and thymus atrophy (p < 0.01), higher DAI scores (p < 0.01), shorter colons (p < 0.05), worse inflammation (elevated IL-6 and MPO) and gastrointestinal dysfunction (reduced GAS and elevated MTL) (p < 0.01), and unique kidney yang deficiency damage (elevated kidney index, p < 0.01), along with sustained weight loss. While both models reflect inflammation and immune dysregulation, the SKYD-UC model better simulates the refractory nature of UC, offering an effective animal model for UC research.
Yang S, Xie F, Lin X, Zhang Y, Wang Y, Huang Y, Zhang X, Hao Y, Zhou H, Fu C
UC-associated autoantibodies to αvβ6 inhibit mucosal TGFβ activation and predispose to intestinal inflammation. bioRxiv : the preprint server for biology | 2026-03-16
Ulcerative colitis (UC) is characterized by epithelial barrier dysfunction and dysregulated mucosal immune responses; however, the mechanisms driving disease onset remain poorly defined. Autoantibodies against the epithelial-restricted integrin αvβ6 are a highly specific biomarker of UC that can precede clinical diagnosis by up to 10 years. Because αvβ6 activates TGFβ at epithelial surfaces, we hypothesized that UC-associated αvβ6 autoantibodies inhibit mucosal TGFβ activation and disrupt epithelial homeostasis. We showed that αvβ6 autoantibodies were enriched in UC and that IgG from autoantibody-positive individuals inhibited αvβ6-dependent activation of TGFβ. αvβ6 blockade dampened TGFβ signaling and altered differentiation-associated gene programs in human intestinal epithelial cells. In mice, deletion of αv caused expansion of inflammation-associated goblet cells in the colon and changes in intestinal immune cells. Using a novel mouse model, we showed that αvβ6-specific autoantibody disrupted epithelial-immune crosstalk and increased susceptibility to DSS colitis. Together, these findings establish anti-αvβ6 autoantibodies as active inhibitors of epithelial TGFβ signaling, constituting a de facto anti-cytokine response, rather than passive biomarkers. By linking preclinical seropositivity to impaired epithelial signaling and heightened susceptibility to colitis, this work identifies epithelial αvβ6-dependent TGFβ activation as a pathway that may be leveraged to modify disease risk or limit disease severity. UC-associated autoantibodies impair epithelial TGFβ activation, alter mucosal homeostasis, and predispose to colitis.
Fasano KJ, Yoshida AE, Madden JF, Mauk KE, Tung LW, Edwards TH, Shows DM, Stefani C, Kugler DG, Scheiding S
Huanglian muxiang decoction alleviates FTH-mediated ferroptosis in colitis by inhibiting the PI3K-AKT pathway. Phytomedicine : international journal of phytotherapy and phytopharmacology | 2026-03-14
Dysregulated iron metabolism and subsequent ferroptosis play a critical role in the pathogenesis of ulcerative colitis (UC), highlighting iron homeostasis as a therapeutic target. Huanglian muxiang decoction (HMD), a traditional Chinese herbal formula, is widely utilized for gastrointestinal disorders such as colitis. However, its underlying molecular mechanisms remain unclear. To identify the active compounds in HMD and elucidate its molecular mechanisms of action in alleviating UC, specifically concerning iron metabolism and ferroptosis. Mice were given drinking water containing 3 % dextran sulfate sodium (DSS) for a period of 7 days. After a 3-day interval, mice were randomly assigned to treatment groups and orally administered HMD (4.29, 8.58, or 17.16 g/kg) or sulfasalazine (SASP; 250 mg/kg) once daily for 7 days. Additionally, intestinal-specific FTH knockout mice (FTHflox/flox; Villin-Cre) were treated with low-dose HMD (4.29 g/kg) using the same protocol. Network pharmacology was employed to predict potential therapeutic targets of HMD against UC, followed by validation in both in vivo and in vitro models. The active compounds in HMD were identified using UHPLC-HRMS. A mouse model of colitis was employed to evaluate the effects of HMD on disease symptoms (body weight, fecal occult blood, survival rate, disease activity index), colon length, inflammation, histopathology, and tight junction protein expression (Occludin, ZO-1). Network pharmacology and functional analyses were used to predict involved signaling pathways. Mechanistic investigations included assessments of mitochondrial structure, iron overload, and the levels of ferroptosis-related proteins (GPX4, FTH). The critical role of FTH was further validated using intestinal-specific FTH knockout mice. Additionally, co-immunoprecipitation (co-IP), cellular thermal shift assay (CETSA), and surface plasmon resonance (SPR) analyses were performed to explore the PI3K-AKT-FTH pathway, while immunoprecipitation-mass spectrometry (IP-MS) was used to identify potential intermediary effectors. Multiple active compounds, including alkaloids, flavonoids, and phenylpropanoids, were identified in HMD. HMD treatment significantly alleviated colitis symptoms, improved intestinal integrity, and increased tight junction protein expression, with a low dose showing effects comparable to SASP. Mechanistically, HMD was found to regulate iron metabolism and inhibit ferroptosis via the PI3K-AKT pathway, as evidenced by restored mitochondrial structure, reduced iron overload, and increased expression of GPX4 and FTH. Intestinal-specific knockout of FTH aggravated colitis and attenuated the protective effects of HMD, confirming FTH as a key mediator. Further assays suggested that p-AKT indirectly regulates FTH, potentially through transcription factors or kinases, supporting a PI3K-AKT-FTH regulatory axis. Our findings demonstrate that HMD attenuates colitis by modulating ferroptosis via the PI3K-AKT-FTH pathway.This study provides novel insights into the therapeutic mechanisms of HMD and highlights its potential as a natural remedy for UC treatment.
Wang Y, Li T, Wang Y, Li J, Song L, Fu Y, Li W, Li L, Qiu Y, Yan J
Therapeutic potential of Qihuang Biwen Formula and its bioactive compounds for the treatment of ulcerative colitis in Drosophila and mice. Phytomedicine : international journal of phytotherapy and phytopharmacology | 2026-03-14
Qihuang Biwen Formula (QHBWF), derived from the classic Yupingfeng Powder, is traditionally used for immune regulation. While clinically applied, its mechanism of action in ulcerative colitis (UC) remains unclear. The effectiveness and underlying principles of QHBWF for UC treatment were investigated using both Drosophila and mice models, and its bioactive components were identified. In the dextran sulfate sodium (DSS)-induced adult fly, the survival rate, locomotion, excretion, smurf, digestive capacity, intestinal length, death of intestinal epithelial cells (IECs), and proliferation of intestinal stem cells (ISCs) were measured. Meanwhile, the body weight, intestinal length, disease activity index, histopathology, serum cytokine levels, and ROS levels were detected in the UC mouse. Additionally, the mechanism of QHBWF was investigated by bioinformatics analysis, transcriptomic analysis, qRT-PCR, immunohistochemistry and western blotting (WB). Finally, UCPL-MS/MS technology and phenotype assays in UC flies were used to screen the key bioactive components of QHBWF. QHBWF significantly improved survival rate, locomotor activity, and intestinal function. It restored intestinal morphology, suppressed aberrant intestinal stem cell (ISC) proliferation, and reduced intestinal epithelial cell (IEC) apoptosis in DSS treated flies. In mice, QHBWF alleviated weight loss, colon shortening, and DAI scores, improved histopathology, and reduced IL-6, IL-1β, and intestinal ROS. These results indicated that QHBWF could alleviate the intestinal injury in both UC models. Mechanistically, QHBWF down-regulated mRNA levels of Toll signaling and the Imd signaling, and up-regulated the gene expression of mitochondrial oxidative phosphorylation (OXPHOS) complexes in the intestines of UC flies. Consistently, QHBWF decreased the protein levels of TLR4, MyD88 and NF-κB p65, and promoted the protein expresses of NDUFB8, SDHB and ATP5A in the guts of UC mice. These indicated that QHBWF inhibited the TLR4/NF-κB signaling pathway and activated the OXPHOS function. Furthermore, kaempferol, emodin, quercetin, isochlorogenic acid, and chlorogenic acid could extend the survival rate, increased the intestinal length, and facilitated intestinal barrier repair in UC flies. QHBWF exerted anti-colitis effects by regulating immunity and metabolism, targeting the TLR4/NF-κB signaling pathway and mitochondrial oxidative phosphorylation. Kaempferol, emodin, quercetin, isochlorogenic acid, and chlorogenic acid were the bioactive compounds of QHBWF against UC. This study provides the potential of QHBWF as a multi-target treatment for UC.
Wang H, Xiu M, Zhou S, Zhang Y, Fu J, Jiang X, Zhao B, Liu Y, Zhang Z, He J
Chemical Profiling and Mechanistic Insights into Stichopodidae Viscus Extract for Ulcerative Colitis via UPLC-IMS-Q-TOF-HDMSE and Network Pharmacology. Pharmaceuticals (Basel, Switzerland) | 2026-03-12
Background: The visceral organs of sea cucumbers belonging to the family Stichopodidae, also known as Stichopodidae Viscus (SV), have been traditionally used for the management of gastrointestinal disorders. Experimental evidence has shown that the ethanol extract of SV (SVE) alleviates ulcerative colitis (UC) symptoms in a mouse model. However, the chemical constituents of SVE and the potential molecular targets mediating its effects in UC remain unclear. Methods: In this study, SVE was prepared from Apostichopus japonicus (Selenka). A reliable and sensitive strategy integrating advanced analytical and informatics tools was employed to profile the chemical components of SVE. Analyses were performed using ultra-performance liquid chromatography coupled with ion mobility spectrometry and quadrupole time-of-flight mass spectrometry operating in high-definition MSE (UPLC-IMS-Q-TOF-HDMSE), with data processed using the UNIFI scientific information system. Constituent identification relied on retention time (RT), accurate mass (MS1), experimentally acquired HDMSE (MS2) spectra, and collision cross-section (CCS). Metabolomics-based approaches were further applied to characterize the in vivo exposure profile of SVE components in mouse serum and colon tissue after oral administration. Subsequently, the putative bioactive constituents and their underlying mechanisms of action were investigated using network pharmacology and molecular docking. Results: Based on the integrated identification strategy, a total of 78 compounds, including saponins, phenolic acids, fatty acids, and amino acids, were annotated in SVE, among which 6 compounds were verified using authentic reference standards to ensure unambiguous identification. Subsequently, 35 features in serum and 24 in the colon were found to be significantly altered following a single oral dose of SVE in mice, and were defined as SVE-related differential constituents. After network pharmacology analyses, 129 shared targets were identified between potential targets of SVE-related components in serum and UC-related targets, including PIK3CA, EGFR, and AKT1. Functional enrichment analysis suggested that SVE might exert its effects in UC through modulation of key nodes within the PI3K-Akt and EGFR signaling pathways, as well as lipid- and atherosclerosis-related pathways. Molecular docking results further indicated moderate binding affinities of representative SVE-related differential components toward PIK3CA, AKT1, and EGFR. Conclusions: This study clarifies the chemical basis and potential UC-related mechanisms of SVE, providing a scientific rationale for the development of SV-derived therapeutic candidates for UC.
Wang L, Liu Y, Chen N, Xiao S, Yang S, Lv Z
Xu Chunfu’s Modified Xianglian Pill Regulates the NOX2/ROS/Mitochondria/NLRP3 Axis to Treat Ulcerative Colitis. Pharmaceuticals (Basel, Switzerland) | 2026-03-11
Background/Objectives: Xu Chunfu’s Modified Xianglian Pill (XXLP) has been used for centuries in Chinese medicine to treat “diarrhea” and “dysentery,” conditions analogous to modern ulcerative colitis (UC). However, the scientific basis for its efficacy and mechanisms remains unclear. Methods: The chemical composition of XXLP was analyzed via UPLC-ESI-MS/MS. A colitis mouse model was established using DSS, and the therapeutic effects were assessed based on body weight, disease activity index (DAI), colon length, and histopathology. Inflammatory cytokines were measured using ELISA. Proteomic analysis and molecular docking identified key targets, which were validated using LPS-induced HT-29 cells via Western blot (WB), qRT-PCR, immunofluorescence (IF), and transmission electron microscopy (TEM). Gut microbiota composition was analyzed using 16S rRNA gene sequencing. Results: Analysis of XXLP led to the detection of 373 compounds. XXLP significantly improved colitis symptoms, including weight loss and colon shortening, and reduced the concentrations of inflammatory markers IL-1β, IL-18, TNF-α, and IL-6. Proteomics and molecular docking identified NADPH oxidase 2 (NOX2) as a key target of XXLP intervention in mice with colitis. qRT-PCR, WB, IF, and TEM results further confirmed that XXLP effectively suppressed the expression of NOX2 and its associated protein levels. Sequencing analysis of 16S rRNA showed that XXLP significantly increased the relative abundance of beneficial bacterial genera (Muribaculaceae and Ruminococcaceae) while markedly reducing the levels of harmful bacteria (Enterobacteriaceae). Correlation analysis revealed that specific microorganisms were correlated with NOX2-related protein expression and severity of colonic inflammation. Conclusions: XXLP effectively alleviates colitis by suppressing inflammatory responses. Its mechanism involves regulating the NOX2/ROS/mitochondria/NLRP3 axis and altering gut microbiota composition, providing novel insights for colitis treatment.
Mao S, Wang Y, Bu Q, Xu Z, Wei W, Wu D, Hu R, Wang C, Wang T, Yang Y
Purified Diets Lacking Fermentable Fiber Reduce Microbial Diversity, Alter Epithelial Transcriptome, and Exacerbate Colitis. Nutrients | 2026-03-11
Background/Objectives: Dietary fibers play key roles in shaping gut microbiome and intestinal homeostasis. While purified diets offer experimental precision and reproducibility in rodent models, they omit the complex mixture of fermentable and non-fermentable fibers found in grain-based chow diets. We hypothesized that excluding fermentable fiber impairs intestinal homeostasis by reducing microbial metabolites and altering the colonic epithelial transcriptome, thereby increasing susceptibility to inflammation. Methods: Wildtype male C57BL/6 mice were maintained on either a standard grain-based chow diet or a purified low-fat diet (LFD) containing 5% non-fermentable cellulose for ten weeks. Fecal microbiomes, short-chain fatty acid (SCFA) profiles, and colonic epithelial transcriptomes were analyzed. A separate group was challenged with dextran sodium sulfate (DSS) following a five-week dietary intervention to compare colitis severity between the two diet groups. Results: Relative to mice fed the grain-based chow, those consuming the purified LFD (containing only non-fermentable cellulose) showed decreased gut microbial diversity and significantly lower SCFA levels. These changes were accompanied by marked differences in colonic epithelial cell transcriptomes. In LFD-fed mice, the top upregulated gene networks included ribosomal pathways and MHC complex protein binding, suggesting increased growth and gut inflammation. The most downregulated pathways included mineral absorption, actin and tubulin binding, and membrane organelle assembly, indicating major alterations in cellular structure and transport. LFD-fed mice also exhibited increased colonic expression of S100a9, a gut inflammation biomarker, and more severe disease symptoms when challenged with DSS compared to chow-fed mice. Conclusions: Fermentable fibers are one of the factors contributing to intestinal homeostasis and mitigating the severity of ulcerative colitis.
Thomas EG, Ortutu BF, Watson JC, Ong E, Blankley KE, Meaurio Martin A, Shankar S, Zhang D, Boland DJ, Wu CS
CU104, a novel barrier function enhancer, improves colitis via modulation of barrier function and immune cell recruitment. Frontiers in immunology | 2026-03-10
Inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, is a chronic and relapsing condition with complex pathogenesis and limited therapeutic options. The efficacy of CU104, a novel blocker of endothelial dysfunction, in IBD models is poorly understood. Moreover, its precise cellular or molecular mechanisms in colitis remain unknown. To evaluate the therapeutic potential of CU104, we tested CU104 in two colitis models: dinitrobenzene sulfonic acid (DNBS)-induced colitis in wild-type mice and dextran sodium sulfate (DSS)-challenged colitis in IL-10 knockout mice. Additionally, we used Caco-2, HCT-116, and HT-29 cells to assess CU104 effects on intestinal barrier function (FITC-dextran permeability and TEER), inflammatory signaling (reporter assays), actin dynamics, and gene expression (gene expression profiling and immune assays). CU104 demonstrated potent suppressive effects on innate immune responses, intestinal and vascular barrier dysfunctions, and immune cell recruitment in these colitis models. Furthermore, CU104 inhibited the activation of the transcription factors nuclear factor kappa-light-chain-enhancer of activated B cells and interferon regulatory factor, as well as the ezrin/radixin/moesin (ERM) signaling pathway, both in vitro and in vivo, by modulating actin dynamics. Consistent with these findings, CU104 improved the functions of vascular and intestinal barriers and regulated immune cell recruitment during inflammation. Collectively, our findings demonstrate that CU104 can regulate actin dynamics and inflammatory signaling pathways, highlighting potential therapeutic targets for IBD.
Park IS, Kim JH, Kim D, Kim YW, Shin Y, Kim KB, Zhang H, Kim TI, Kim SW, Kwon YG
Drug Safety & Pharmacovigilance (11 papers)
Adverse Events and Safety Outcomes Associated With Chemotherapy for Inflammatory Bowel Disease-associated Gastrointestinal Cancers. Anticancer research | 2026-04
Management of inflammatory bowel disease-associated gastrointestinal cancers, including Crohn’s disease-associated cancer and ulcerative colitis-associated cancer, remains challenging because of concerns regarding treatment-related toxicity and limited clinical data. We aimed to investigate the safety of chemotherapy in patients with inflammatory bowel disease-associated gastrointestinal cancer. This retrospective study analyzed 21 patients with inflammatory bowel disease-associated gastrointestinal cancer (Crohn’s disease-associated cancer: 10; ulcerative colitis-associated cancer: 11) who received chemotherapy or chemoradiotherapy between 2010 and 2024. Chemotherapy regimens, adverse events, treatment completion rates, and residual small intestinal lengths in patients with Crohn’s disease were evaluated. Oxaliplatin-based chemotherapy was the most commonly used chemotherapeutic regimen. Dose reduction was required in all patients with Crohn’s disease-associated cancer and in 64% of those with ulcerative colitis-associated cancer, primarily because of diarrhea or neurotoxicity. In the Crohn’s disease-associated cancer group, diarrhea occurred in all patients and was significantly more severe in those with shorter residual small intestines (p=0.02). Despite these toxicities, 80% of patients with Crohn’s disease-associated cancer and 55% of those with ulcerative colitis-associated cancer completed the planned chemotherapy regimen. No inflammatory bowel disease flares or need for corticosteroids or biologics occurred during treatment. Chemoradiotherapy was administered to five patients with Crohn’s disease-associated cancer and locally advanced anorectal cancer, with no major safety concerns. Chemotherapy, including chemoradiotherapy, can be safely administered to patients with inflammatory bowel disease-associated gastrointestinal cancer with careful management. In Crohn’s disease-associated cancer, residual small intestinal length is a key factor in predicting gastrointestinal toxicity severity, particularly diarrhea. Individualized dose adjustments and close monitoring are essential to balance cancer treatment efficacy with the unique risks associated with inflammatory bowel disease.
Hasegawa N, Ogino T, Sekido Y, Takeda M, Hata T, Hamabe A, Miyoshi N, Uemura M, Eguchi H, Doki Y
LAG-3 at the crossroads: A context-dependent regulator of Tregs and autoimmunity inflammatory disorders.Review Life sciences | 2026-03-27
This review aims to systematically examine the regulatory mechanisms of Lymphocyte Activation Gene 3 (LAG3) in modulating T regulatory cell (Treg) function and its context-dependent implications in major inflammatory and autoimmune diseases. We conducted a comprehensive literature review synthesizing findings from basic research, preclinical animal models, and clinical studies investigating LAG3 expression and function across autoimmune conditions, including rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, autoimmune diabetes, inflammatory bowel disease, and psoriasis. LAG3 exhibits dual, context-dependent roles in autoimmunity. In multiple sclerosis and rheumatoid arthritis, LAG3+ Tregs exert protective immunosuppressive functions via IL-10 and TGF-β. Conversely, in systemic lupus erythematosus and psoriasis, LAG3 expression can mark unstable Tregs transitioning to pathogenic IL-17-producing phenotypes. LAG3 also modulates Treg metabolic programming, IL-2/STAT5 signaling, and cooperates with other checkpoints like PD-1. Soluble LAG3 (sLAG-3) is elevated in several autoimmune diseases, but its functional significance remains unclear. Understanding LAG3’s context-dependent regulation of Tregs is crucial for developing precision immunotherapies. Future strategies should move beyond broad LAG3 blockade toward subset-specific modulation to restore immune tolerance in autoimmune diseases.
Yu Z, Tang X, Shi Y, Gong Y
STING pathway contributes to Steroid-Hyporesponsive Lung Inflammation in DSS-induced colitis mice model. PloS one | 2026-03-27
Inflammatory bowel disease (IBD), a chronic inflammation of the gastrointestinal tract, is well recognized for triggering extraintestinal manifestations, including pulmonary complications. Emerging evidence highlights the gut lung axis (GLA) as a critical link in respiratory health, where gut dysbiosis and bacterial translocation play a role in systemic and pulmonary inflammation. Despite its clinical relevance, the mechanisms underlying these pulmonary manifestations remain poorly understood. The Stimulator of Interferon Genes (STING) pathway plays a critical role in regulating pulmonary inflammation. However, its precise role in colitis-associated lung inflammation remains unclear and could provide novel insights into the pathogenesis of this condition. This study evaluates the involvement of STING pathway in colitis induced lung tissue inflammation using a dextran sulfate sodium (DSS) murine model of colitis. The effect of STING inhibitor on regulating steroid hypo-responsiveness, particularly the glucocorticoid receptor GR-α/GR-β ratio, is also examined. The DSS model induces lung inflammation, characterized by enhanced infiltration of inflammatory cells into lung tissues, increased levels of IL-17, IFN-γ, bacterial DNA, while enhancing steroid hypo-responsiveness. The inhibition of STING controls lung inflammation and restores steroid sensitivity to a much higher extent compared to dexamethasone treatment. The significant activation of the STING pathway and dysregulation of steroid signature markers in the lungs of DSS-induced colitis mice suggest a novel mechanism by which gut inflammation may propagate to the lungs.
Eladham MW, Sharif-Askari NS, Mdkhana B, Ali S, Al-Sheakly BKS, Ali N, Selvakumar B, Sharif-Askari FS, Hachim I, Halwani R
Managing Acute Severe Ulcerative Colitis in the Older Patient: A Growing Concern.Review Drugs & aging | 2026-03-26
Since the prevalence of older patients with ulcerative colitis is increasing, hospitalizations for severe disease in this age group are expected to rise. Older patients are more likely to present with comorbidities and, consequently, frailty, the latter being one of the major drivers of worse outcomes. The conventional sequencing of therapies in acute severe ulcerative colitis-i.e., intravenous steroids followed, in case of refractoriness, by antitumor necrosis factor (TNF) agents, ciclosporin A, or Janus kinase inhibitors such as tofacitinib or upadacitinib-may frequently be contraindicated in older patients or may carry an increased risk of severe adverse events beyond infections. In the absence of specific guidelines, the implementation of and strict adherence to a structured, time-bound decision tree is essential in order to avoid unnecessarily prolonged treatment with systemic steroids in frail patients, which may lead to deleterious outcomes, particularly in those requiring surgery. Recent reports on adjunctive measures, such as hyperbaric oxygen therapy or total enteral nutrition, may also be considered given their encouraging safety profile.
Fries W, Costantino G, Viola A
Longitudinal Safety Outcomes of Anti-tumor Necrosis Factor Alpha Therapy in the Treatment of Inflammatory Bowel Disease. Digestive diseases and sciences | 2026-03-24
Short- and medium-term safety profiles of anti-TNF therapies are well-established, but data on their long-term safety, especially beyond five years, remain limited. This study aims to compare the risk of adverse events (AEs) in patients on stable anti-TNF therapy for less than five years versus more than five years. A retrospective cohort study was conducted in an outpatient IBD clinic from April 2015 to November 2023. Patients were divided into short-term (less than five years) and long-term (more than five years) therapy groups. AEs were tracked across multiple systems, and time-adjusted risks were compared using multivariable Cox proportional hazards models. We identified 640 patients (785 instances) receiving stable anti-TNF therapy. A total of 82 AEs were reported over 1774 person-years. The AE incidence per 100 person-years was 5.12 in the short-term group and 3.50 in the long-term group with no significant adjusted risk between groups (aHR, 0.62; 95% CI 0.35 to 1.11). However, patients with CD on long-term infliximab therapy signaled a lower risk of AEs compared to short-term users (aHR, 0.33; 95% CI 0.11 to 1.00). Dermatologic events were the most common AEs. Long-term anti-TNF therapy appears to have a similar safety profile to short-term therapy, with no significant increase in overall AE risk. These findings may offer cautious reassurance regarding extended anti-TNF use, particularly in patients with CD on infliximab.
Roney AR, Orr D, Barghi A, Hussani S, Cusumano V, Limketkai BN, Sauk JS
Positive conversion of latent tuberculosis screening in patients with inflammatory bowel disease on antitumor necrosis factor alpha drugs: a systematic review and meta-analysis. European journal of gastroenterology & hepatology | 2026-03-23
Inflammatory bowel disease (IBD) patients undergoing antitumor necrosis factor-alpha (anti-TNF) therapy are at increased risk of developing tuberculosis (TB), making screening before anti-TNF initiation mandatory. Repeated screening during treatment is not yet recommended because of a lack of studies to support this practice. We aimed to determine the proportion of patients who develop latent TB during anti-TNF therapy. We systematically searched studies from MEDLINE, Embase, and Lilacs, and performed a single-arm meta-analysis investigating the positive conversion rate in IBD patients under anti-TNF therapy with previous negative TB screening. We calculated the combined proportion with 95% confidence interval, using the random-effects model. A P value less than 0.05 was considered statistically significant for subgroup differences. We included 13 studies from nine countries with 1153 patients. The overall positive conversion rate was 9.20%. Portugal had 18.01% of positive conversion, Spain 4.51%, and the USA 1.11%. Tests for subgroup differences were statistically significant for subgroup analysis by country and consistency of test used (performig same test as baseline). Subgroup analyses by continent, study design, or specific test (tuberculin skin test or interferon-gamma release assay) showed no statistical difference. Meta-regression analysis showed a significant positive association between positive conversion and TB incidence. In conclusion, IBD patients on anti-TNF therapy can have a positive conversion rate of 9.20%. Higher conversion rates were seen in European and Asian studies compared with those in the Americas (particularly the USA). TB prevention strategies should, therefore, be individualized and based on geographic location and risk factors.
Rzetelna H, Santo P, de Souza HSP, Nichols J, Zaltman C
Functional Evaluation of Computationally Designed IL-10 in IL-10 KO Mice. Biomolecules | 2026-03-23
Studies have shown that IL-10 has therapeutic potential for inflammatory diseases. However, it is challenging to use IL-10 as a therapeutic drug because it also possesses pro-inflammatory functions. To reduce these pro-inflammatory effects of IL-10, we have designed three IL-10 mutants using structure-based computational design technology. We demonstrated that these mutants exhibited significantly lower activity in IL-10-responsive cell lines than wild-type IL-10. Using recombinant adeno-associated virus (rAAV8) vectors expressing wild-type or mutant IL-10 molecules, we performed gene therapy experiments in IL-10 KO mice. The results showed that our vectors mediated high levels of transgene expression. Importantly, IL-10 gene therapy increased body weight gain, reduced colon injury, and prevented the development of inflammatory bowel disease (IBD). Moreover, IL-10 mutant gene therapy elicited significantly lower stimulation of CD8 T and NK cells compared with the wild-type IL-10 group. In summary, our IL-10 mutants provide a protective effect comparable to wild-type IL-10 in the IL-10 KO mouse model, suggesting that they may potentially have reduced pro-inflammatory function. While rigorous investigations of safety and efficacy in different disease models will be required, these results indicate the therapeutic potential of IL-10 mutant gene therapy for inflammatory diseases such as IBD.
Stokes J, Hyder I, Shen Z, Ramdhan P, Bayer A, Wasserfall C, Li C, Song S
Clinical Case Report on the Use of Rezafungin in Pneumocystis jirovecii Pneumonia in a Critically Ill Patient.Case report Microorganisms | 2026-03-18
Pneumocystis jirovecii pneumonia (PJP) is a life-threatening opportunistic infection predominantly affecting immunocompromised patients. Trimethoprim-sulfamethoxazole (TMP-SMX) remains the standard therapy but is often limited by severe toxicity. Rezafungin, a next-generation echinocandin with a long half-life, has shown preclinical activity against Pneumocystis spp., but its use in humans remains largely unexplored. We report the case of a 67-year-old man with inflammatory bowel disease who developed severe PJP complicated by acute respiratory failure, septic shock, and multiorgan dysfunction following corticosteroid and biologic therapy. Standard TMP-SMX therapy was contraindicated due to renal impairment and pancytopenia. The patient received rezafungin via a compassionate-use programme, with serial monitoring of serum and bronchoalveolar β-D-glucan levels. Despite a partial biomarker response, the patient ultimately progressed to refractory acute respiratory distress syndrome and multiorgan failure. This case provides preliminary human data suggesting that rezafungin may offer a potential therapeutic option for PJP when standard treatment is contraindicated or poorly tolerated. Close clinical and biomarker monitoring is essential. Further clinical and experimental studies are warranted to determine its efficacy, optimal dosing, and safety in critically ill immunocompromised patients.
Fernández-Fernández R, García-Martínez R, Fernández WS, Chueca-Porcuna N, Colmenero-Ruiz M
Preventive Effect of Chenopodium formosanum Koidz. on Dextran Sulfate Sodium-Induced Chronic Colitis in Mice. Nutrients | 2026-03-18
Background: Chenopodium formosanum Koidz. (djulis) is an indigenous cereal crop native to Taiwan, and its effects on patients with inflammatory bowel disease (IBD) warrant exploration. The present study investigated whether the consumption of djulis can alleviate chronic colitis induced by dextran sulfate sodium (DSS) in mice. Methods: Forty mice were randomly divided into five groups: blank group (B), control group (C), low-dose group (L), medium-dose group (M), and high-dose group (H). Body weight and disease activity index (DAI) were recorded throughout this study. Groups C, L, M, and H were administered 2% DSS water on days 1-5 and 10-15 to induce chronic colitis. Groups L, M, and H were administered 5%, 10%, and 15% djulis, respectively. Serum and colon samples were collected for further analysis. Results: The DAI scores of groups L, M, and H were significantly lower than those of group C (p < 0.05), and the DAI scores of group H on day 18 were significantly lower than those of group L (p < 0.05). Colon length analysis revealed that DSS intervention significantly shortened colon length in group C (p < 0.05), whereas mice consuming djulis (groups L, M, and H) exhibited a restoration of colon length, with the effect being most pronounced in group H. DSS significantly increased the secretion of certain pro-inflammatory cytokines in the serum, such as interleukin (IL)-1β (p < 0.05), and the expression of some pro-inflammatory proteins in the colon, such as the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) (p < 0.05); however, djulis reversed these effects (especially in group H). In addition, mice in group H exhibited beneficial gut microbiota. Conclusions: Djulis alleviated chronic colitis in mice by reducing inflammation and modulating the gut microbiota. Further research is required to confirm these potential benefits in humans and elucidate the mechanisms involved.
Yeh HJ, Chao HM, Chang CC, Kao WY, Yang SC, Chao JC, Shih CK
Chest X-ray prior to biological treatment in inflammatory bowel diseases: it is not only about tuberculosis - a case report and literature review. European journal of gastroenterology & hepatology | 2026-03-16
Biological treatments have substantially improved management of inflammatory bowel disease, but their profound immunosuppressive effects necessitate infection screening before initiation. Current guidelines recommend chest X-ray (CXR) alongside Mycobacterium tuberculosis testing. While this approach is widely accepted, the necessity of routine CXR in patients without tuberculosis (TB) risk factors has recently been questioned in low-incidence regions. We report a rare case of a patient with ulcerative colitis undergoing routine preinfliximab CXR revealing an apical right-lung infiltrate, that was not suspected based on clinical assessment and negative interferon-gamma release assays testing. In addition, we summarize the existing literature on invasive aspergillosis associated with tumor necrosis factor alpha inhibitors. The patient had minimal clinical symptoms of pulmonary infection and remained afebrile with consistently normal C-reactive protein levels. Nevertheless, routine pretreatment CXR demonstrated an apical right-lung infiltrate, leading to cancelation of planned infliximab initiation. Subsequent analyses of bronchoalveolar fluid and sputum identified two strains of Aspergillus fumigatus. Despite prolonged antifungal therapy, the patient ultimately required a right-lung lobectomy. A comprehensive literature review identified three fatal cases of invasive aspergillosis following tumor necrosis factor alpha inhibitors, underscoring the clinical importance of detecting serious pulmonary infections prior to treatment initiation. Our case is, to our knowledge, the first report in inflammatory bowel disease to illustrate that CXR may uncover potentially life-threatening infections beyond TB in patients with limited clinical and biochemical signs of infection, supporting its continued role in prebiologic treatment workflows even in low-TB prevalence settings.
Binder IMH, Brynskov J, Attauabi M
Identification of Drug Repurposing Opportunities of Immunomodulatory Drugs for Inflammatory Bowel Disease Through Inverse Pharmacovigilance Signal Detection in the FAERS Database. Journal of clinical medicine | 2026-03-12
Background/Objectives: Drug repurposing represents a promising strategy to expand therapeutic options for inflammatory bowel disease (IBD), a chronic condition with persistent unmet clinical needs. This study aimed to identify existing drugs with potential relevance for IBD by exploring inverse associations in the FDA Adverse Event Reporting System (FAERS) as a hypothesis-generating, real-world data approach. Methods: In this retrospective observational pharmacovigilance study, drug-IBD associations were extracted from the FAERS database using OpenVigil 2.1. Inverse associations were identified based on reporting odds ratios (ROR) < 1 with adjusted p-values < 0.05. Identified drug-event pairs were further evaluated for pharmacokinetic feasibility, clinical applicability, and biological plausibility in the context of IBD, with the exclusion of drugs with implausible indications, contraindications, or mechanisms inconsistent with IBD pathophysiology. Given the immune-mediated nature of IBD and the breadth of the identified candidates, detailed evaluation focused on immunomodulatory agents. Results: Among the 3585 initial drug-IBD combinations, 73 candidates met the predefined criteria for statistical significance and feasibility. From these, nine drugs were prioritized based on inverse signal strength and mechanistic relevance to immune modulation pathways implicated in IBD. The strongest inverse association with IBD was observed for lenalidomide (ROR 0.056, 95% CI 0.043-0.073), followed by dupilumab (ROR 0.213, 95% CI 0.185-0.245), cyclophosphamide (ROR 0.215, 95% CI 0.175-0.265), fingolimod (ROR 0.216, 95% CI 0.205-0.334), dimethyl fumarate (ROR 0.332, 95% CI 0.275-0.400), apremilast (ROR 0.357, 95% CI 0.296-0.431), imatinib (ROR 0.423, 95% CI 0.339-0.527), glatiramer acetate (ROR 0.446, 95% CI 0.352-0.565), and interferon beta-1a (ROR 0.594, 95% CI 0.533-0.662). These agents possess immunomodulatory properties relevant to inflammatory pathways implicated in IBD; however, clinical evidence supporting the therapeutic efficacy of some candidates remains variable or incomplete. Conclusions: By integrating inverse signal detection with clinical and biological assessment, this study demonstrates how pharmacovigilance data can be extended from traditional safety surveillance toward systematic drug repurposing applications. The findings generate testable hypotheses and highlight candidate therapies that warrant further experimental and clinical investigation in IBD.
Đogatović K, Vučićević K, Kovačević M, Ćulafić M, Miljković B, Kovačević SV
Biomarkers & Precision Medicine (8 papers)
TET1 deficiency amplifies macrophage inflammatory signaling associated with Crohn’s disease. Inflammation research : official journal of the European Histamine Research Society … [et al.] | 2026-03-27
To define the role of Ten-Eleven Translocation (TET) proteins in Crohn’s disease (CD)-associated inflammation through integrative human and mechanistic studies. Publicly available CD transcriptomic and DNA methylation datasets, and primary mononuclear cells and ileal biopsies were analyzed for TET gene expression and signatures. TET1 and TET2 CRISPR/Cas9 knockout macrophage cell lines were generated. Macrophages were stimulated with LPS in the presence or absence of kinase inhibitors. Conditioned media from macrophages were applied to primary human neutrophils. PBMCs from CD patients and healthy donors were stimulated with LPS for validation. Macrophages or primary patients samples were analyzed by high-throughput surface marker profiling, RNA sequencing, 5hmC sequencing, assays of effector function, qRT-PCR, phosphoflow, and cytokine/chemokine release by ELISA. TET1 was the most downregulated TET enzyme in CD blood and ileal tissues, correlating with reduced TET-associated gene signatures and elevated inflammatory mediators. TET1-deficient macrophages exhibited distinct surface phenotypes, reduced PTEN expression, altered 5hmC distribution, and heightened IFN gene expression, ERK activation, and chemokine release associated with enhanced neutrophil migration. PBMCs from CD patients mirrored reduced TET1 expression and exaggerated inflammatory responses. TET1 functions as a non-redundant regulator of inflammatory macrophages and aberrant chemokine signaling linked to immune cell recruitment in Crohn’s disease.
Perez RK, Paul R, Kumar P, Tutkun A, Webb D, McGorty S, Wieckowski T, Yap YS, Leesang TE, Vlantis PI
Immunoinformatic-based design of a multi-epitope subunit vaccine against Ruminococcus torques using subtractive proteomics and molecular dynamics simulations. Scientific reports | 2026-03-26
Ruminococcus torques is an anaerobic, Gram-positive gut bacterium that has been associated with gastrointestinal diseases including irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). Its mucolytic effect disrupts the integrity of the intestinal barriers, which are involved in dysbiosis and pathogenicity. Recent clinical evidence has also reported its involvement in extraintestinal infections like pneumonia, keratitis, bacteremia and ocular infection in immunocompromised individuals. Although, R. torques has emerged as a clinically more significant pathogen, no vaccine is yet approved against it, highlighting the urgent need for novel prophylaxis strategies. The primary objective of this investigation was to employ bioinformatics and immunoinformatics strategies in the construction of a candidate multi-epitope vaccine. The complete proteome of Ruminococcus torques strain ATCC 27,756 was obtained and subjected to a series of analyses to find strong B- and T-cell epitopes with high antigenicity, non-allergenicity and non-toxicity. Key proteins such as cell division protein FtsX, single-stranded DNA binding protein and probable peptidoglycan glycosyltransferase FtsW were identified as the final target candidates. A multi-epitope vaccine was designed by linking the selected epitopes with the assistance of suitable spacers and adjuvant. The three-dimensional structure of the vaccine was modeled, refined and validated by in-silico approach. Furthermore, the protein-protein molecular docking was conducted to define probable binding poses on the multi-epitope vaccine against the Toll-like receptor (TLR4) protein. The stability of the vaccine-receptor complex was further validated by molecular dynamics simulation. In silico cloning of the vaccine construct yielded a GC content of 49.29% and a Codon Adaptation Index (CAI) of 0.875 indicating maximum expression potential in the host system. Although computational analyses provide valuable insights, experimental validation is required to confirm the immunogenicity and protective efficacy of the vaccine proposed.
Kousar S, Manzoor I, Muhammad S, Almohaimeed HM, Hasan T, Fenibo EO, Matambo T
Intestinal Stem Cells from Patients with Inflammatory Bowel Disease Retain an Epigenetic Memory of Inflammation.★ Cellular and molecular gastroenterology and hepatology | 2026-03-26
Intestinal epithelial damage and impaired repair are hallmarks of ulcerative colitis (UC), even after inflammation resolves. Intestinal stem cells (ISCs) can retain stable epigenetic changes after inflammation, highlighting the potential for long-lived epithelial memory in the gut. Inflammatory injury in barrier tissues induces epigenetic memory in epithelial stem cells, and the tendency of UC to relapse at previously inflamed sites led us to hypothesize that ISCs from IBD patients acquire lasting memory of prior inflammation. To test this, we derived colonic organoids from inflamed (I) and noninflamed regions of the same UC patients and propagated in long-term culture. Chromatin profiling revealed 2,252 accessible regions unique to I organoids, associated with stress response, repair, and inflammatory genes. Although these regions remained accessible, ∼95% of associated genes were not upregulated in I organoids, indicating a primed state. Upon inflammatory or injury re-challenge, I organoids exhibited heightened transcriptional responses and accelerated wound closure, despite reduced clonogenicity and impaired barrier function, indicating a retained inflammatory memory program. Our findings demonstrate that human ISCs retain a chromatin-based memory of inflammation that persists in the absence of immune cues and shapes future responses to injury. While this may support epithelial adaptation to secondary insults, it may predispose tissue to relapse in patients with UC.
Hamdan FH, Farhadipour M, Perez I, Kossick K, Smith H, Edwinson A, de Hoyos-Vega JM, Gonzalez M, Chiang D, Klatt E
Nanospatially confined ROS eliminator produced in situ by engineered Escherichia coli Nissle 1917 for oral treatment of inflammatory bowel disease. Journal of controlled release : official journal of the Controlled Release Society | 2026-03-23
Oral interventions using engineered bacteria are effective for preventing and treating digestive diseases, yet improving bioavailability remains challenging. This study constructed a probiotic pharmaceutical factory using the probiotic Escherichia coli Nissle 1917 (EcN) as the chassis to deliver antioxidant enzymes via in situ oral administration. Engineered bacteria continuously produced nanobiotic reactors by hijacking the endogenous production line of bacterial outer membrane vesicles (OMVs). Protein turnover and outer membrane oxidative stress were used to increase outer membrane instability while promoting OMV generation. The engineered bacteria maintained high antioxidant enzyme expression even in the hypoxic colonic environment, ensuring therapeutic efficacy post-oral administration. Meanwhile, the SpyCatcher/SpyTag self-anchored system enabled targeted encapsulation of protein drugs into OMVs, enhancing programmability and precision. In a dextran sulfate sodium (DSS)-induced ulcerative colitis mouse model, the engineered bacterial factory was shown to reduce inflammation, repair the intestinal epithelial barrier, and regulate gut microbiota. This OMV-targeted encapsulation only requires replacing therapeutic proteins and adding SpyTag to customize factories for different needs, highlighting its potential in clinical digestive disease treatment.
Chen H, Wu J, Shi Q, Zhang Z, Zheng Y, Fan Y, Ren L
Identification and validation of GNA15 as a novel diagnostic biomarker in ulcerative colitis. Journal of molecular histology | 2026-03-23
Abstract not available.
Shi X, Tang Q, Xu Y, Zhu J
Integrative Transcriptomics and Machine Learning Reveal the Association of CBX4 with Inflammation in Ulcerative Colitis as a Potential Epigenetic Regulator. Biomedicines | 2026-03-17
Background/Objectives: Epigenetic factors are increasingly recognized to contribute to the pathogenesis of intestinal diseases, yet the precise mechanisms through which these factors influence ulcerative colitis (UC) remain poorly understood. Methods: Transcriptome profiles pertaining to UC and genes associated with epigenetic factors (EFRGs) were retrieved from publicly accessible datasets. Candidate genes were ascertained through the intersection of differentially expressed genes (DEGs) and EFRGs. Key genes were screened through machine learning algorithms and validated via the Artificial Neural Network (ANN) model. Enrichment analysis and immune infiltration assays were conducted to elucidate the underlying mechanisms of these genes. The hub gene, CBX4 (Chromobox homolog 4), was validated through immunohistochemical analysis of both healthy controls and patients with UC, and the correlation was evaluated using UC-related clinical parameters. Additionally, CBX4 expression was knocked down in dextran sulphate sodium (DSS)-treated mice to examine its regulatory function. Unlike conventional broad-spectrum biomarker screens, this study specifically integrated epigenetic factor-related genes (EFRGs) with machine learning and experimental validation using both clinical samples and animal models. Results: SMARCB1, JAK2, CBX4, and PPARGC1A were identified as key genes, with SMARCB1, JAK2, and CBX4 being upregulated in the UC group, while PPARGC1A was significantly downregulated. The ANN model exhibited excellent diagnostic performance. Enrichment analysis revealed that the key genes were associated with pathways such as the “chemokine signaling pathway”. Immune cell infiltration analysis results revealed marked differences in the abundances of 13 immune cell types between the UC and control groups, and there were notable associations between immune cell infiltration and key genes. Notably, CBX4 expression was elevated in both DSS-treated mice and patients with UC, showing positive correlations with clinical indicators of UC. Further in vivo experiments revealed that silencing CBX4 alleviated DSS-induced colon damage and inflammation. Conclusions: This study identifies four EFRG-related key genes (SMARCB1, JAK2, CBX4, PPARGC1A) in UC, suggesting that CBX4 may play a significant role as an epigenetic regulator. CBX4 is upregulated in UC intestinal tissues, and its knockdown mitigates DSS-induced colitis. These findings provide critical theoretical support for developing targeted therapies for UC.
Ma X, Liu G, Gong T, Liu X
Renshen-Baidu-San restores epithelial-immune crosstalk and drives type 2 immune repair in ulcerative colitis: an integrated multi-omics study. Frontiers in immunology | 2026-03-11
Ulcerative colitis (UC) is a chronic inflammatory disease of the colonic mucosa characterized by recurrent flares and difficulty achieving sustained remission. Renshen-Baidu-San (BDS), a classical Chinese herbal prescription, has shown promising clinical benefit in relieving UC symptoms, but its underlying therapeutic mechanisms remain insufficiently defined. This study aimed to elucidate the multiple biological mechanisms underlying the therapeutic effects of BDS in UC. We utilized an integrated multi-omics and experimental approach, combining serum metabolomics, pharmacological network analysis, molecular docking, and single-cell RNA sequencing in a DSS-induced UC mouse model, supplemented by colon organoid experiments. Key findings were validated using histopathology, immunohistochemistry, immunofluorescence, quantitative RT-PCR, ELISA, and flow cytometry. Serum metabolomics demonstrated that BDS modulates steroid- and lipid-derived metabolites, thereby influencing steroid hormone biosynthesis, bile acid turnover, and lipid pathways including arachidonic acid and linoleic acid metabolism. Network pharmacology based on serum-detected components further highlighted BDS’s regulatory effects on inflammatory signaling and cellular proliferation, while molecular docking identified stable and favorable protein-ligand interactions. Single-cell transcriptomics revealed that BDS corrected UC-induced epithelial-immune dysregulation, with Tuft and T-1 cell subclusters emerging as key responders through coordinated suppression of NF-κB-driven TNF-α signaling; ligand-receptor analysis indicated restoration of epithelial-immune communication. Colon organoid experiments corroborated mucosal repair, crypt structural recovery, Tuft cell expansion, and a shift toward a tissue-restorative type 2 immune profile, characterized by elevated IL-4 and IL-25 and reduced IL-13. Our findings indicate that BDS treatment in DSS-induced colitis is accompanied by alterations in metabolic pathways, epithelial-immune communication, and cell-type-specific transcriptional programs, which may be relevant to type 2 immune-mediated mucosal repair processes.
Liu J, Liu X, Zhang W, Song L, Xu Y, Yang Y, Xiong P, Jia B
Cold Exposure Alleviates Colitis via Parallel Integration of Colonic Mucosal Regeneration and Ileal Antimicrobial Defense. Biomedicines | 2026-03-09
Background: Inflammatory bowel disease (IBD) involves chronic intestinal inflammation, epithelial barrier disruption, and dysbiosis, with environmental factors playing a significant role in its pathogenesis. Previous work revealed that cold exposure alleviates colitis in mice; this study extends that finding by demonstrating that cold exposure enhances intestinal regeneration even in healthy mice, upregulating proliferation markers (Mki67, PCNA, Cyclin D1). Methods: Applying this pro-regenerative effect to a colitis model, we investigated the underlying mechanisms through multi-omics analysis, transmission electron microscopy (TEM), immunofluorescence, and pathological staining as well as 16S rRNA sequencing. Results: We found that cold exposure activates intestinal epithelial proliferation pathways. Further analysis indicated that cold exposure induces colonic stem cell regeneration, upregulating stem cell markers Lgr5 and Ascl2. Notably, colonic transcriptomic profiling revealed the emergence of a Paneth-like cell phenotype, characterized by altered expression of specific lineage genes. Furthermore, cold exposure simultaneously promoted the accumulation of secretory granules and upregulated the expression of antimicrobial peptide genes (such as Lysozyme and Defa) in ileal Paneth cells. This enhanced ileal antimicrobial defense effectively reshaped the gut microbiota in inflamed intestines. Conclusions: This research elucidates a mechanism whereby cold adaptation promotes mucosal repair by integrating localized colonic epithelial regeneration with enhanced ileal Paneth cell-mediated antimicrobial defense. This offers compelling new perspectives on how environmental factors, such as cold exposure, could influence the pathophysiology of IBD and contribute to intestinal regeneration, which may provide foundational theoretical support for the future diagnosis and treatment of IBD.
Di Y, Deng J, Hong Z, Liu Z, Jin L, Zhao W, Qu B
Pediatric IBD (8 papers)
Evaluating the impact of therapeutic drug monitoring strategies on clinical outcomes in paediatric inflammatory bowel disease. Journal of pediatric gastroenterology and nutrition | 2026-03-27
The increasing incidence of inflammatory bowel disease (IBD) in paediatric populations underscores the importance of effective management strategies. Anti-tumor necrosis factor (anti-TNF) agents, such as infliximab (IFX) and adalimumab (ADL), are key treatments for inducing and maintaining remission in IBD, but many patients experience a loss of response over time. Different strategies of therapeutic drug monitoring (TDM) are applied to optimise anti-TNF therapy. In this study, we investigated the effect of proactive and reactive TDM on clinical outcomes and pharmacokinetic parameters in paediatric IBD patients. We conducted a retrospective multicentre study involving 391 children with IBD from the CEDATA-GPGE registry. Patients were categorised into proactive (n = 285) and reactive (n = 106) TDM groups. Clinical outcomes, laboratory results, and pharmacokinetic parameters of IFX and ADL were compared between the groups. Proactive TDM was associated with higher clinical remission rates (50% vs. 24%, p < 0.0001) and reduced hospitalisation rates (17% vs. 39%, p < 0.0001) compared to reactive TDM. In Crohn’s disease patients, proactive TDM was linked to lower disease activity and improved levels of C-reactive protein and erythrocyte sedimentation rate. Proactive TDM was also associated with higher IFX drug levels, lower anti-drug antibody concentrations and less frequent switches of the biological therapy. Differences in pharmacokinetic parameters during ADL-treatment were less pronounced and no significant benefit of proactive TDM was observed. Our data suggest that proactive TDM may offer clinical and pharmacokinetic benefits, particularly for paediatric IBD patients treated with IFX, while results for other outcomes and for ADL were less clear. Prospective studies are needed to confirm these findings and to further clarify the role of proactive TDM in this population.
Hubert KP, Stricker S, Laffolie J
Impact of 5-ASA discontinuation in children with ulcerative colitis on biologic therapy: A propensity score-matched study. Journal of pediatric gastroenterology and nutrition | 2026-03-26
5-Aminosalicylic acid (5-ASA) is recommended as a first-line medication in mild to moderate ulcerative colitis (UC), but indications regarding its use in children with moderate to severe disease treated with biologics are lacking. We aimed to evaluate the impact of discontinuing 5-ASA in children with UC treated with anti-tumor necrosis factor (anti-TNF) anti-tumor necrosis factor (anti-TNF). Retrospective, multicenter, case-control study of the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition inflammatory bowel disease (IBD) study group. Children with UC starting anti-TNF therapy between January 2018 and January 2023 and with a minimum follow of 6 months were included. Those who discontinued 5-ASA (cases) were compared to those who continued mesalamine (controls). A Propensity Score analysis was used to match 1:2 with patients by baseline clinical and demographic characteristics. Every 6 months, during a 2-year follow-up, data on disease flares, IBD-related hospitalization, surgery, need for step-up treatment and acute severe colitis were recorded. Data from 298 children were collected (92 [31%] cases and 206 [69%] controls) and 227 were included in the final analysis after matching (85 [37.5%] cases and 142 [62.5%] controls]. Children who discontinued 5-ASA were at higher risk of courses of steroids (Log-Rank p = 0.003) and hospitalization (p = 0.08). At the multivariate Cox regression analysis, 5-ASA discontinuation was identified as an independent predictor of courses of steroids (p = 0.003) and hospitalization (p = 0.08). 5-ASA discontinuation might negatively impact the clinical course of children with UC treated with anti-TNF. Considering the good safety profile of the drug, continuing mesalamine can be suggested as a prudent approach.
D’Arcangelo G, Scarallo L, Mancuso G, Corpino M, Romano C, Norsa L, Arrigo S, Bramuzzo M, Fioretti MT, Zuin G
High-Dose Opioid Use Among Adolescents and Young Adults with Chronic Digestive Disorders. Digestive diseases and sciences | 2026-03-26
High-dose opioid use (≥ 50 morphine milligram equivalents [MME]/day) is associated with increased risk of adverse outcomes, including overdose. We investigated the prevalence and risk factors for high-dose opioid use among adolescents and young adults (AYA) with inflammatory bowel disease (IBD) and other chronic digestive disorders to inform safer pain management strategies. This retrospective cohort study identified AYA aged 15-29 years with chronic digestive disorders who received ≥ 1 outpatient opioid prescription between March 2018 and December 2021, using Northwestern Medicine’s Electronic Data Warehouse. Short-term persistent high-dose opioid use was defined as a daily mean of ≥ 50 MME/day for ≥ 7 consecutive days. Patients were categorized into high-dose vs. non-high-dose users. We examined demographic and clinical covariates (e.g., race/ethnicity, insurance status, psychiatric diagnoses, GI and non-GI pain diagnoses, concurrent medications) using descriptive and bivariate analyses. Risk factors for high-dose use were identified via multivariate logistic regression. Among 2549 AYA patients, 12% met criteria for high-dose opioid use. Risk factors included older age within the cohort, benzodiazepine-opioid co-use, oxycodone use, and concurrent non-GI pain diagnoses (e.g., arthritis). Nearly 12% of AYA with chronic digestive disorders who used opioids for ≥ 7 days received high-dose prescriptions. These findings underscore the need for safer prescribing guidelines tailored to this population. Future work should consider weight-based dosing thresholds and expanded datasets to monitor and reduce opioid-related harm in AYA with digestive disorders.
Yarlagadda S, Huang L, Dharanipragada D, Younan M, Arshad A, Paniagua-Perez D, Rech MA, Raval MV, Balbale SN
Upper and small bowel Crohn’s disease in Brazilian children: Phenotypic characteristic and surgical risk. Journal of pediatric gastroenterology and nutrition | 2026-03-26
Upper and small bowel Crohn’s disease (U-SBCD) represents a clinically aggressive phenotype with high complication rates yet remains diagnostically challenging. In low- and middle-income countries (LMICs), limited inflammatory bowel disease (IBD) awareness contributes to diagnostic delays, but their impact on U-SBCD outcomes remains poorly characterized. We aimed to characterize clinical features, management patterns, and surgical outcomes of pediatric U-SBCD in Brazil, establishing IBD baseline for future regional comparisons in LMIC setting. This multicenter retrospective study analyzed 124 pediatric Crohn’s disease (CD) patients (diagnosed < 18 years) from six Brazilian centers according to revised PORTO-ESPGHAN criteria. Patients with U-SBCD (Paris L4a/L4b, n = 39) were compared to non-SBCD (L1/L2/L3). Univariate and multivariable analyses assessed demographics, diagnostic delay, disease behavior, growth impairment, and therapeutic outcomes over 18 months follow-up. The population comprised predominantly African-Brazilian admixture. U-SBCD patients presented at older age (median 14 vs. 12 years; p = 0.001) with greater height impairment (p = 0.010) and lower body mass index (BMI)/age z-scores (-1.14 vs. -0.44; p = 0.029). Severe weight loss (z-score < -2) conferred 8.3-fold increased U-SBCD odds (95% confidence interval [CI]: 2.17-31.66; p = 0.002). Each year of diagnostic delay increased U-SBCD odds by 22% (95% CI: 1.06-1.39; p = 0.004). U-SBCD patients required more biologic therapy (97% vs. 75%; p = 0.003) with higher treatment escalation rates (31.6% vs. 21.2%; p = 0.004). Multivariate analysis confirmed U-SBCD as an independent three-fold predictor of surgery (OR 3.02; 95% CI: 1.02-8.94; p = 0.046). A 9-year-old girl with U-SBCD died perioperatively. Psychiatric symptoms affected 30% of both groups. In LMIC settings, strengthening medical education is essential to improve early recognition of U-SBCD and prevent progression to irreversible complications. Notably, the phenotypic pattern observed in our study more closely resembled that reported in Asian pediatric patients than Caucasian cohorts.
Oba J, Sobrado CW, Lomazi EA, Deboni M, Marmo MCDR, Scheeffer VA, Carvalho SDR, Damião AOMC, Azevedo MFC, Marques CFS
Multi-system inflammatory syndrome in a child with Crohn’s disease- a diagnostic dilemma.Case report Oxford medical case reports | 2026-03-23
Post-covid multisystem inflammatory syndrome in children (MIS-C) can cause life-threatening inflammation in children, particularly in those with underlying conditions like Crohn’s disease (CD). The overlap of symptoms between CD flares and MIS-C can create diagnostic and therapeutic challenges, necessitating high-level clinical suspicion and aggressive management when both conditions coexist. We present a 14-year-old boy, with a 3-year history of CD, who presented with diarrhea, abdominal pain, and weight loss. Investigations revealed anemia, thrombocytosis, hypoalbuminemia, and elevated inflammatory markers and fecal calprotectin. He was treated with methylprednisolone and methotrexate. On day 25 of admission, he developed altered sensorium, inability to ambulate, and hypoxia. He was found to have left ventricular dysfunction, non-hepatic hyperammonemia and cerebral sinus thrombosis. Work-up revealed a pro-inflammatory state with elevated serum ferritin, interleukin-6, d-dimers and positive anti-Covid IgG, and led to the diagnosis of MIS-C overlapping with CD flare. He was treated with intravenous immunoglobulin and recovered.
Dhanjani B, Tetarbe S, Gandhi D, Shah I
Five children with haploinsufficiency of A20 caused by heterozygous mutations in the TNFAIP3 gene.Case report Frontiers in immunology | 2026-03-11
Children with A20 haploinsufficiency, resulting from heterozygous variants in the TNFAIP3 gene, are increasingly being identified. However, their diagnosis and treatment remain challenging and are not yet fully optimized. The clinical, genetic characteristics and treatment methods of five children with HA20 from different families were collected from Henan Children’s Hospital between April 2019 and August 2023 to evaluated for accumulating experience in the management of this rare condition. We identified five heterozygous variants in the TNFAIP3 gene among the five children, including c.866delA: p.H289Pfs* 3, c.1243_1247delAAAAC: p. N416Tfs* 11, NC_000006.11: g.136693638_138817508del, c.133C>T: p.R45X, c.1903_1906delAAAC: p. K635fs* 61. All patients were de novo (they have all been tested to confirm their origin). Besides, patient 3 also harbored two MMACHC gene mutations: c.349G>C: p.A117P–inherited from the parents and c.482G>A: p.R161Q –de novo. Variants in patients 3 and 5 have not been reported. All five patients presented with childhood-onset recurrent fever and intermittent diarrhea, which are hallmark features of HA20. Additionally, two of the five patients experienced intermittent bloody stool, three had oral ulcers, and two presented with skin symptoms, further aligning with the clinical manifestations of HA20. Laboratory tests revealed elevated inflammatory markers, including increased white blood cell (WBC) counts, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). Endoscopic observation, there were ulcers in different parts of the intestine. Each child was treated with the oral drug thalidomide, 4 children (80%) received glucocorticoids to reduce inflammation, and had different biological agents according to individual differences. During follow-up, we observed significant improvement in all children who received targeted treatment. HA20 is a rare monogenic early-onset auto-inflammatory disease. It can present with a variety of clinical manifestations, including Behcet disease, inflammatory bowel disease, lupus-like syndrome and periodic fever syndrome. Whole-exome sequencing should be actively considered for children who present with early-onset symptoms or features suggestive of autoimmune diseases.
Yao H, Liu Y, Dong M, Yang K, Yu Z, Zhou F
Efficacy and safety of dual-targeted therapy in children with inflammatory bowel disease: Retrospective cohort study. World journal of clinical pediatrics | 2026-03-09
There is a limited number of studies on the efficacy and safety of dual-targeted therapy (DTT) in children with inflammatory bowel diseases (IBD); the latest reports focus on the combination of biological drugs with Janus kinase inhibitors (JAKI). To evaluate the efficacy and safety of DTT in children with IBD. This retrospective cohort study included 18 IBD patients, aged 2-17 years, with 13 (72%) having Crohn’s disease (CD) and 5 (28%) having ulcerative colitis, who were treated with DTT. In two children, two different combinations of DTT were used sequentially. The data on clinical and laboratory changes were assessed at the beginning of DTT and at three months (M3) and six months (M6). Fecal calprotectin and endoscopy were evaluated at baseline and M6. A total of 20 courses of DTT in 18 patients were included in the analysis: (1) 12 (60%) were treated with JAKI and vedolizumab; (2) 6 (30%) with JAKI and ustekinumab; and (3) 2 (10%) with JAKI and adalimumab. Clinical remission was achieved in 9/20 (45%) and 13/20 (68%) DTT courses in patients within M3 and M6, respectively. In contrast, laboratory and endoscopic remission (ER) were achieved in 8/20 (40%) and 9/17 (53%) patients, respectively, within M6. Perianal lesions and upper gastrointestinal tract involvement were negatively associated with the efficacy of the DTT in CD patients. Children with early onset of the disease are more likely to achieve ER compared with those with later onset: 8/11 (73%) vs 1/6 (17%), respectively. Side effects were reported in 6/20 (30%) of cases, and 5/6 (83.3%) were considered non-serious. A DTT may be considered for children with refractory IBD. This strategy was shown to be most effective among children with a very early onset of the disease.
Gabrusskaya T, Ulanova N, Shilova E, Volkova N, Kilina S, Kornienko E, Kostik M
Gastrointestinal consequences of cesarean section birth: A systematic review of short- and long-term effects in infancy and beyond. World journal of clinical pediatrics | 2026-03-09
Cesarean section (C-section) delivery rates are rising globally, raising concern about their potential long-term health consequences on offspring. Emerging evidence suggests that C-section, by bypassing the physiological and microbial exposures of vaginal birth, may adversely affect neonatal gastrointestinal (GI) development and immune regulation. To evaluate the short- and long-term gastrointestinal outcomes in infants born via C-section, compared to those born vaginally. A systematic literature search was conducted across PubMed, Scopus, and Web of Science for studies published from inception to 2024. Studies were included if they reported gastrointestinal outcomes among C-section-born infants and included a vaginal delivery comparison group. Outcomes of interest included short-term disorders (infantile colic, gastroesophageal reflux, constipation, dyschezia, and functional gastrointestinal disorders) and long-term conditions (inflammatory bowel disease, food allergies including cow’s milk protein allergy, celiac disease, and microbiota dysbiosis). Data extraction and synthesis were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. C-section -born infants demonstrated a higher risk of several short-term GI disturbances, including infantile colic, reflux, and constipation. These outcomes were consistently associated with early gut microbiota dysbiosis, characterized by reduced microbial diversity and delayed colonization by Bifidobacteria and Bacteroides. Long-term associations with C-section included a modest increase in the risk of Crohn’s disease, cow’s milk protein allergy, and food sensitization, while the links with ulcerative colitis and celiac disease were inconsistent. Breastfeeding, probiotic/synbiotic supplementation, and limited antibiotic exposure emerged as protective modifiable factors. C-section delivery is associated with a higher risk of adverse gastrointestinal outcomes in infancy and childhood, driven in part by early-life gut microbial disruption. Preventive strategies targeting microbial restoration and immune modulation, particularly breastfeeding and probiotic interventions, may help mitigate these risks. Clinicians should be aware of these associations to guide personalized care and parental counseling, particularly in elective C-section deliveries.
Al-Beltagi M, Alzayani S, Saeed NK, Bediwy AS, Prabu Kumar A, Bediwy HA, Elbeltagi R
Surgery & Complications (8 papers)
Risk factors for postoperative complications in Crohn’s disease: A systematic review and meta-analysis. Advances in clinical and experimental medicine : official organ Wroclaw Medical University | 2026-03-30
Crohn’s disease (CD) is a non-specific inflammatory bowel disorder for which no definitive cure is available. The primary management strategy is pharmacological treatment aimed at alleviating symptoms. However, many patients ultimately require surgical intervention to manage complications arising from the disease. The aim of this study was to investigate disease-related factors that may increase the risk of early postoperative complications in patients with CD. A meta-analysis was conducted based on studies examining early surgical and medical complications following abdominal surgery for CD. The analyzed risk factors included disease duration prior to surgery, history of previous surgeries, presence of concurrent perianal disease, intra-abdominal abscess during surgery, and Montreal classification subtypes A1-3, L1-4, and B1-3. A systematic review was performed using 4 major databases: PubMed, Cochrane Library, Academic Search Ultimate (EBSCO), and Google Scholar. Outcomes were assessed using the odds ratio (OR) and response ratio (R), together with 95% confidence intervals (95% CIs). Egger’s test was used to evaluate publication bias. Heterogeneity was assessed using the I2 statistic, with I2 > 50% indicating significant variability. A total of 51 articles met the inclusion criteria. The analysis identified several significant risk-increasing factors: history of previous surgeries (OR = 1.39; 95% CI: 1.23-1.57), Montreal classification group B3 (OR = 1.26; 95% CI: 1.11-1.42), disease duration before surgery (R = 1.10; 95% CI: 1.02-1.18), and group L2 (OR = 1.38; 95% CI: 1.11-1.72). Conversely, factors associated with a reduced risk of postoperative complications included group L1 (OR = 0.81; 95% CI: 0.71-0.92) and group B2 (OR = 0.81; 95% CI: 0.71-0.91). This meta-analysis aggregated data from a broad spectrum of patients and treatment settings across multiple institutions worldwide. Although some risk of bias and heterogeneity was observed, the findings nevertheless highlight the importance of considering disease subtype and progression when assessing the likelihood of postoperative complications in patients with CD. This knowledge may be valuable for optimizing treatment strategies.
Łosińska J, Lewandowski M, Kawiński A, Dziki AJ, Mik M
Development and external validation of a predictive model for postoperative recurrence of Crohn’s disease in the biologic era. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association | 2026-03-27
Ileocolonic resection remains common in Crohn’s disease (CD) despite increasing biologic use. to identify risk factors for postoperative recurrence and to assess prophylactic biologic therapy effectiveness in relation to risk factors. This prospective multicentre study included adults with CD undergoing ileocolonic resection (ICR). The primary endpoint was endoscopic recurrence (modified Rutgeerts Score ≥i2b) within the year following surgery. Factors associated with endoscopic recurrence were identified using a logistic regression model. A composite time-to-event endpoint was defined for long-term follow-up based on clinical, endoscopic and/or imaging data. An external validation of our predictive model was performed in two independent international cohorts. Among 632 patients (median disease duration 7.8 years), 78% had prior biologic exposure; 44% received postoperative biologic prophylaxis. Endoscopic recurrence occurred in 237 (37.5%) patients. In multivariable model, risk factors included: male sex (OR 1.97 (95%CI: 1.38, 2.83), active smoking (OR 2.37 (95%CI: 1.56, 3.62), previous ICR (OR 1.78 (95%CI: 1.13, 2.82), previous exposure to one (OR 2.15 (95%CI: 1.37, 3.42) or more than one biologic (OR 2.41 (95%CI: 1.39, 4.22). Biologic prophylaxis significantly reduced recurrence risk (OR 0.31 (95%CI: 0.20, 0.45), independently of these risk factors. A predictive nomogram based on multivariable analysis achieved an AUC of 0.72, with similar performance in external cohorts. Clinically significant recurrence, observed in 22.9%, 36.5% and 53.2% at 3, 5 and 10 years, was associated with severity of early endoscopic recurrence. Postoperative recurrence risk can be estimated using a model based on clinical factors. Biologic prophylaxis is highly effective in preventing early endoscopic recurrence, regardless of risk profile.
Allez M, Bak MTJ, Brand S, Diebakate-Scordamaglia L, Capelle E, Seksik P, Nancey S, Gornet JM, Buisson A, Carbonnel F
Intracorporeal Versus Extracorporeal Anastomosis in Crohn’s Disease: Recurrence and Perioperative Outcomes After Minimally Invasive Ileocecectomy. ANZ journal of surgery | 2026-03-27
Minimal-invasive surgery (MIS) was proven beneficial in Crohn’s Disease (CD). Intracorporeal anastomosis (ICA) represents a further improvement as it is associated with decreased complications and shorter hospitalization. Extracorporeal anastomosis (ECA) is preferred to ICA as it allows haptic feedback of the bowel and mesentery, which is historically required for bowel resection in CD to minimize recurrences. We compared ICA and ECA in terms of recurrences and complications. All patients between 2016 and 2022 with Crohn’s disease who underwent a MIS ileocecectomy were identified and divided into ICA and ECA groups. Exclusion criteria were open surgery, end ileostomies, follow-up < 1 month, and ileocecectomy not due to CD. 107 patients were included in the ICA group (44.9% male, mean age of 40.2 [±16.6] years), while 270 patients were in the ECA group (46.7% male, mean age of 41.9 [±17.3] years). The rate of endoscopic recurrences with a Rutgeerts score > 2, clinical recurrence, and surgical recurrence were not statistically different between the two cohorts. On the multivariable analysis for endoscopic and clinical recurrences, the ICA/ECA approach was not significant. The ECA group revealed a higher overall complication rate (30.4% versus 15.9%, p = 0.004). The median length of stay was significantly reduced in the ICA group (p < 0.001). ICA seems to be safe in ileocecectomies for CD. The complication rate and length of stay were reduced while not affecting the endoscopic, clinical, and surgical recurrence rates. MIS technology provides enhanced visualization and haptic feedback, which could be used as surrogates for the tactile evaluation intra-operatively.
Sassun R, Keshk N, Sileo A, Perry WRG, Behm KT, Shawki SF
Evaluation of serum and dietary profiles of vitamin B12 and folate and their association with systemic complications in patients with Crohn’s disease. European journal of clinical nutrition | 2026-03-27
Crohn’s Disease (CD) is a chronic inflammatory bowel disease that affects micronutrient levels, impacting metabolic pathways. Homocysteine (Hcy) levels, regulated by folate and vitamin B12, are associated with cardiovascular and extraintestinal manifestations (EIMs). This study aims to analyze the dietary intake and serum concentrations of folate and vitamin B12 and their relationship with systemic complications in patients with CD in remission and active phases. This cross-sectional study included 60 patients, and nutrient intake was stratified into tertiles by disease phase. The metabolic safety of folate and B12 was evaluated by characterizing metabolic risk patterns associated with elevated Hcy. Statistical analyses evaluated associations between dietary intake, metabolic safety, and disease phenotype. Vitamin B12 intake was negatively associated with erythrocyte sedimentation rate and positively associated with the absence of EIMs. Serum folate and non-HDL cholesterol levels were lower in the active group. Clinical vitamin B12 deficiency was more frequent in active disease, contributing to an elevated Hcy risk. Stricturing/penetrating phenotypes showed lower vitamin B12 levels compared to non-stricturing, non-penetrating phenotypes. Additionally, 96% of patients with structuring/penetrating disease were at high Hcy risk, while 30% of patients with non-stricturing, non-penetrating disease were in the lowest risk category. The data suggest that folate and B12 levels could be markers for clinical characteristics and associated metabolic risk in patients with CD. Our study highlighted associations that may justify the importance of nutritional follow-up and biochemical assessments in the clinical routine of patients with CD.
de Castro MM, Dos Santos VN, Gomes MS, Ferraz ADG, Ignacio-Souza LM, Torsoni MA, Torsoni AS, Ayrizono MLS, Leal RF, Corona LP
Conversion of Barnett continent reservoir to Kock reservoir: A 30-year retrospective study on surgical outcomes and long-term follow-up. Techniques in coloproctology | 2026-03-27
The Barnett continent reservoir has long been used as a surgical option for patients requiring continent ileostomies, but complications such as valve leakage, obstruction, and pouch failure often necessitate revisions. Conversion to a Kock (K) pouch offers an alternative with potentially improved outcomes. This study evaluated the safety (postoperative complications), feasibility (technical completion of conversion), and effectiveness (long-term pouch salvage) of conversion. We conducted a retrospective cohort study of patients who underwent Barnett-to-K-pouch conversion (conversion group) or remained with a Barnett pouch (non-conversion group) between 1991 and April 2024. The conversion technique included disconnection of the afferent limb, preservation and 180° rotation of the reservoir, resection of the collar valve, creation of a stapled nipple valve, and pouch-neo-afferent limb anastomosis. Demographics, surgical history, and long-term follow-up were collected. Pouch salvage was defined as retention of a functional continent pouch; failure was defined as excision with permanent ileostomy. Out of 30 patients with Barnett pouch patients included, 16 underwent conversion and 14 did not. Median age was 51.5 versus 60.5 years, and median body mass index (BMI) was 24.7 versus 22.3 kg/m2 in conversion versus non-conversion groups, respectively. Ulcerative colitis was the primary indication (62.6% versus 78.8%). Leading revision causes were valve slippage (50% versus 35.7%) and fistula (18.7% versus 28.6%). Pouch salvage was higher with conversion (81.3%, 95% confidence interval [CI] 54-96%) versus non-conversion (35.7%, 95% CI 13-65%; p = 0.03). Long-term follow-up (median: 159.5 versus 301.6 months,) showed that 60% of all patients in conversion group retained continent pouches, while the remaining experienced pouch excision, indicating an overall failure rate of 40%. Conversion of Barnett to K-pouch improves pouch salvage and reduces failure. While technically complex, the procedure can be safely offered to motivated patients seeking to avoid permanent ileostomy.
Alipouriani A, Duraes LC, Liska D, Holubar SD, Steele SR, Lavryk O
AVB-114 Demonstrates Clinical Benefit in Persistent Crohn’s Perianal Fistulas: Randomized Cohort Results from the Multicenter STOMP2 Trial.★ The American journal of gastroenterology | 2026-03-25
Advanced therapies infrequently achieve complete fistula closure in patients with Crohn’s disease (CD). The primary objective of the STOMP2 clinical trial was to determine whether the implantable autologous cell therapy AVB-114 is effective in inducing remission of persistent Crohn’s perianal fistulas versus standard of care. Eligible patients had a single perianal fistula tract and had failed prior treatment or had documented medication intolerance to biologic or conventional CD therapy. All enrolled subjects underwent surgical fistula optimization and adipose tissue biopsy collection (in order to manufacture AVB-114) followed by 1:1 randomization to either standard of care (repeat fistula optimization including seton replacement) or AVB-114 implantation. The primary endpoint was combined fistula remission at 36 weeks, defined as closure of the external opening, no drainage of fluid despite gentle finger compression, and no collections >2cm in at least two of the three dimensions on MRI. Subjects at 14 U.S. sites were equally randomized to SoC (N=24) or AVB-114 (N=24). Week 36 combined remission was 8.3% and 45.8% for subjects randomized to SoC and AVB-114, respectively (38% difference, 95% CI 11-60%; p=0.0078). At Week 36, MRI revealed no subjects with collections >2cm, radiological improvement (≥50% decrease in the MAGNIFI-CD score from baseline) in 1 SoC subject and 3 AVB-114 subjects, and radiological healing (complete resolution of T2-weighted hyperintensity in fistula tract) in 2 SoC subjects and 5 AVB-114 subjects. Through Week 36, there were 40 and 56 treatment emergent adverse events (TEAE) for SoC and AVB-114, respectively. There were no serious TEAEs in the AVB-114 group through Week 36. A significantly higher proportion of patients treated with AVB-114 achieved combined remission versus SoC, and the treatment was well tolerated. These data support the safety and efficacy of AVB-114 in persistent Crohn’s perianal fistulas.
Schwartz DA, Dozois E, Ehman E, Faubion W, Hudesman D, Johnson T, Pabla B, Papadakis K, Fleshner P
Inflammatory vs. complicated Crohn’s disease: Long-term outcomes after ileocecal resection.Letter Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver | 2026-03-23
Abstract not available.
Kumar M, Kumari P, Davi S, Venjhraj F, Kumar H, Mehdi ST
Short-term Surgical Outcomes After Transanal Restorative Proctocolectomy With Ileal Pouch-Anal Anastomosis: A Comparison of Close Rectal Dissection And Modified Total Mesorectal Excision. Diseases of the colon and rectum | 2026-03-23
The preferred treatment for patients with medically refractory ulcerative colitis is a restorative proctocolectomy with ileal pouch anal anastomosis. The transanal approach has been adopted in many centers, however the plane of dissection, number of surgical stages and type of anastomosis differ. This results in heterogeneity in existing studies. We aimed to compare short-term surgical outcomes of modified transanal total mesorectal excision and transanal close rectal dissection in the formation of transanal ileal pouch anal anastomosis. Retrospective cohort study. Two referral centers responsible for transanal ileal pouch anal anastomosis in Denmark. Patients above the age of 18 with ulcerative colitis undergoing transanal ileal pouch anal anastomosis from 2015-2023. Surgical complications in the first 30 postoperative days as registered in the surgical records. A total of 176 patients underwent transanal ileal pouch anal anastomosis at the two centers, 78 patients with close rectal dissection and 98 patients with modified transanal total mesorectal excision. There was no significant difference in complications regarding anastomotic leak comprising 3 (4%) and 4 (4%) patients or intra-abdominal abscesses with respectively 2 (3%) and 2 (2%) patients. The data was collected retrospectively and relied on uniformly reported complications. We didn’t calculate a study power but included all consecutive patients. There were comparable complications regarding anastomotic leaks and intraabdominal abscesses in the two groups, indicating they are equally safe procedures. See Video Abstract.
Schmidt MM, Kjær S, Bulut O, Nørager CB, Tøttrup A, Harsløf S, Pachler FR
Epidemiology & Outcomes (7 papers)
Diagnosis of inflammatory bowel disease following symptomatic faecal immunochemical testing - A population based cohort study. The British journal of surgery | 2026-03-26
Inflammatory bowel disease (IBD) and colorectal cancer (CRC) share overlapping symptoms. Faecal Immunochemical Test (FIT) is mandated in UK primary care to triage symptomatic patients suspected of CRC, but the extent to which IBD is identified in these patients remains unclear. We aim to assess the one-year IBD diagnosis rate in symptomatic patients following FIT for suspected CRC, and how this varies with age, FIT, and faecal calprotectin (FCP). A population-based cohort study of symptomatic patients undergoing FIT in the UK Clinical Practice Research Datalink (CPRD) (January 2019-June 2023), with one-year follow-up was conducted. Kaplan-Meier estimates were used to assess cumulative one-year IBD-risk, stratified by age, FIT, and FCP results. 2762 of 473402 (0·58%) patients were diagnosed with IBD within one-year of FIT. Patients under 50 years (N=110501) accounted for 53·6% of all IBD diagnoses, but only 6·9% of all CRC diagnoses (N=347). Overall IBD-risk was 2·3% with FIT≥10µgHb/g compared to 0·1% with FIT<10µgHb/g. Among 63469 patients with elevated FCP and FIT, IBD-risk in those under 50 years was 21·0% when FIT≥10µgHb/g and FCP>50µg/g. The combined risk of CRC or IBD in those with FIT≥10µgHb/g was 7·1%. This fell to 3·3% in the subset of patients who also had FCP ≤50µg/g. IBD is more common than CRC in patients under 50 years referred on symptomatic FIT pathways using a FIT≥10µgHb/g threshold. In a selected cohort of dual-tested patients, FCP provided additional risk stratification. Incorporating routine FCP into symptomatic FIT pathways may better target further investigations. Inflammatory bowel disease (IBD) is a disease caused by inflamed bowel and can cause symptoms like bowel cancer. In the UK, a stool test called the faecal immunochemical test (FIT), which detects blood in the stool, is used by GPs to decide which patients with bowel symptoms should be tested for cancer. It is not clear how often IBD is diagnosed in these patients. This study looked at how often IBD is diagnosed within a year of a FIT test, and how this varies with age, FIT results, and faecal calprotectin (FCP), a stool marker of inflamed gut. We studied patients in the UK with bowel symptoms who had a FIT test between January 2019 and June 2023, using a database called the Clinical Practice Research Datalink (CPRD). Patients were followed for one year. We calculated the chance of being diagnosed with IBD and compared it across different age groups, FIT results, and FCP levels. Out of 473 402 patients, 2 762 were diagnosed with IBD within a year of a raised FIT. Patients under 50 years made up over half of all IBD diagnoses but only 7% of bowel cancer cases. The chance of IBD was 23 in 1 000 patients if FIT was raised, compared with 1 in 1 000 patients if FIT was not raised. Among patients under 50 years who had elevated FIT and FCP tests, the chance of IBD was 210 in 1 000 patients. Where FIT was raised, a normal FCP lowered than chance of having IBD from 71 to 33 in 1 000 patients. In those under 50 years, if FCP was not raised, the chance of IBD stayed very low (fewer than 40 per 1 000 patients) even with very high FIT results. Adding FCP testing to FIT in patients with bowel symptoms could help doctors target further tests better.
Ng JCK, Morton AJ, Crooks CJ, West J, Grainge MJ, Card TR, Humes DJ
Discordant Clostridioides difficile testing as a predictor of inflammatory bowel disease therapy escalation.★ Inflammatory bowel diseases | 2026-03-25
In patients with inflammatory bowel disease (IBD), Clostridioides difficile infection (CDI) presents with clinical features indistinguishable from the underlying disease. Sequential polymerase chain reaction (PCR) and enzyme immunoassay (EIA) testing reduce overdiagnosis; however, discordant results create management uncertainties. We conducted a retrospective cohort study of IBD patients with positive C. difficile PCR testing at 2 institutions between April 2022 and December 2023. Patients were stratified by EIA toxin (TOX) results. Demographic, clinical, laboratory, and therapeutic data were extracted, and outcomes assessed included CDI-directed therapy or escalation of IBD treatment. Of 575 IBD patients tested, 117 met inclusion criteria. Among them, 79% (93/117) were PCR+/TOX- and 21% (24/117) were PCR+/TOX+. PCR+/TOX+ patients had significantly higher CRP (98 vs 6 mg/L, P = .005). PCR+/TOX- patients had more severe underlying IBD and higher rates of steroid use (48% vs 21%, P = .02) and were less likely to receive CDI treatment (72% vs 96%, P = .01) but were significantly more likely to require IBD therapy escalation (54% vs 25%, P = .004). Multivariable analysis showed PCR+/TOX- status (odds ratio [OR], 3.2; P = .045) and moderate-to-severe endoscopic disease within 1 year of testing (OR, 5.6; P = .0007) were significant predictors of IBD treatment escalation. Elevated CRP may help distinguish true CDI in IBD. PCR+/TOX+ patients typically respond to CDI-directed therapy, whereas PCR+/TOX- patients more often require escalation of IBD treatment, suggesting noninfectious inflammation as the primary driver of symptoms. Among IBD patients with positive C. difficile PCR, escalation of IBD-specific therapy was independently associated with negative toxin EIA and moderate-to-severe endoscopic disease, suggesting that clinical decisions may favor treating an IBD flare despite initial CDI-directed therapy.
Ramakrishnan P, Campbell J, Moutsoglou D, Ghai M, Shmidt E, Vaughn BP
Exposure to per- and polyfluoroalkyl substances and inflammatory bowel disease: review and meta-analysis.Review Journal of exposure science & environmental epidemiology | 2026-03-24
Per- and polyfluoroalkyl substances (PFAS) are stable chemicals that are well preserved in the environment and persist in the human body. PFAS have been associated with inflammatory bowel disease (IBD), but studies are varied in their findings. The objective of this study was to conduct a review of the literature and meta-analysis evaluating PFAS exposure and IBD. PubMed, SCOPUS, Cochrane Library, and the Web of Science were searched for original research articles published in English between 1980 and July 2023 and with human subjects. An adapted risk of bias grading chart was created a priori in order to assess the risks of bias relevant to the studies. For each health outcome, the relative risk point estimates and confidence intervals were used in the synthesis of results. Six studies were identified and assessed for risk of bias. Using random effects meta-analysis for the four studies reporting odds ratios and confidence intervals for serum PFAS concentrations, we found that the average relative increase in ulcerative colitis per 1 ng/mL increase in measured or modeled serum PFOA for these studies is 7% (95% CI: -4.7%, 20.0%). For other PFAS chemicals, there were only three or fewer studies reporting odds ratios for PFAS and IBD. Our results indicate that there is an increased risk of developing ulcerative colitis with increasing serum PFOA; however, the effect is not statistically significant, and has substantial uncertainty. Further research and studies are warranted to enhance the precision of these estimates and clarify the nature of this association. This literature review and meta-analysis evaluate the epidemiologic evidence linking PFAS exposure to irritable bowel disease (IBD)-specifically ulcerative colitis and Crohn’s disease. Results were heterogeneous, and meta-analyses yielded null findings across all PFAS-outcome pairs. Risk of bias due to exposure misclassification, reverse causation, and inadequate control sampling limited confidence in the findings. These results highlight the need for future research and rigorously designed studies to evaluate PFAS as environmental risk factors for IBD.
Phillipson CN, Bartell SM
Risk factors for immune checkpoint inhibitor colitis: a retrospective multi-center cohort study using electronic health records.Multicenter study Cancer immunology, immunotherapy : CII | 2026-03-24
Immune checkpoint inhibitors (ICIs) are effective for many cancers but often cause immune-related adverse events, particularly gastrointestinal (GI) complications such as colitis. Identifying risk factors for ICI colitis (CIC) could improve patient selection and discover potential mechanisms relevant to idiopathic inflammatory bowel disease (IBD). We aim to identify risk factors with a robust methodological approach in a large multi-center longitudinal cohort. We used electronic health record data from six University of California institutions with 10,260 adults on ICIs. Baseline and time-varying predictors were defined based on prior IBD epidemiology studies, including interactions. LASSO Cox regression was applied to data from UCSF Central Data Warehouse to select the most predictive model, with coefficients estimated using multi-center data. Fourteen significant predictors of CIC were identified. The strongest predictors were concurrent use of antibiotics (HR 2.72, 95% CI: 2.41-3.07) and non-steroid anti-inflammatory drugs (1.50, 1.16-1.94). Notable GI risk factors included gastroesophageal reflux disorder (1.31, 1.14-1.50), other GI disorders (1.32, 1.16-1.50), and disorders of the gallbladder, biliary tract, and pancreas (1.33, 1.15-1.57). High BMI before ICI administration increased risk (per unit 1.07, 1.04-1.09), while higher BMI after ICI administration decreased risk (per unit 0.93, 0.90-0.95). Melanoma, anxiety, and depression also increased risk. GI oncologists should consider ICI colitis in patients with comorbid GI disorders or those using antibiotics or NSAIDs. A routine checkup for colitis could be beneficial for those patients. Future studies are needed to explore the underlying mechanisms and quantify clinical impact of increased checkups for colitis.
Chu DHT, Schalkamp AK, Rudrapatna VA
Development and evaluation of a sham diet intended as a placebo-control diet for food-based interventional trials in ulcerative colitis. Journal of the Academy of Nutrition and Dietetics | 2026-03-24
The ‘gold standard’ for successful blinding in controlled food-based dietary interventional trials includes a sham diet. This study aimed to develop and evaluate a sham diet intended for use as a comparator in ulcerative colitis dietary trials. A sham diet to the experimental 4-Strategies to SUlfide REduction (4-SURE) diet was systematically constructed using a six-step process. Healthcare professionals’ naïve to the sham and 4-SURE diet were surveyed to evaluate the impression of the sham diet as an intervention. Healthy adult volunteers then received dietary education and implemented the sham diet for 7-days to evaluate blinding. /setting: Twenty-two health professionals were recruited from the hospital and research institute in Adelaide, South Australia from September - October 2020 to complete the survey. Twenty health professionals met eligibility criteria and completed the survey. Twenty-five healthy adults were recruited via advertisements on notice boards and email distribution lists at the hospital and a university in Adelaide, South Australia from March - June 2021 to complete the 7-day diet trial. Twelve healthy adults met eligibility requirements, agreed to participate and completed the 7-day trial. The combined primary outcome was believability the sham diet could be an intervention diet and success of blinding by asking if the diet was designed to be an intervention or placebo for ulcerative colitis trials. Secondary outcomes included acceptability and tolerability (visual analogue scales), adherence, nutrient intake and dietary education. Descriptive data are presented as mean (95% CI) or median (interquartile ranges (IQR)) for continuous variables. T-tests were used to compare between meal plans and trial time points. Of 20 healthcare professionals surveyed, 19 (95%) agreed both diets impressed a similar complexity and 15/20 (75%) agreed both set meal plans gave the impression of therapeutic dietary prescriptions. Eight (40%) correctly identified the 4-SURE diet. Twelve adults, 10 female and 2 males, completed the sham diet trial. Blinding was successful. All believed the diet could be the intervention diet. The diet was highly tolerable (mean 83 mm; 95% CI 75, 92 mm). The nutrient composition of volunteers’ diets remained uniformly unchanged between baseline and end of 7-days. This sham diet is credible as a therapeutic dietary prescription. It was highly tolerable, did not alter nutrients of therapeutic interest to the 4-SURE diet and is suitable to deploy in food-based trials for ulcerative colitis as a control to diets with a similar dietary scaffold.
Day AS, Ballard TM, Benetti M, Halmos EP, Gibson PR, Yao CK, Bryant RV
Outcomes of Percutaneous Coronary Intervention in Patients with Inflammatory Bowel Disease. Journal of clinical medicine | 2026-03-22
Background: Inflammatory bowel disease (IBD), comprising Crohn’s disease (CD) and ulcerative colitis (UC), has been associated with elevated cardiovascular risks. However, the impact of IBD on outcomes following percutaneous coronary intervention (PCI) remains underexplored. We aimed to evaluate the clinical and procedural outcomes of PCI in patients with concurrent IBD. Methods: This study utilized the National Readmission Database from 2016 to 2020 to evaluate outcomes such as all-cause mortality and post-PCI complications, including various cardiovascular and gastrointestinal (GI) complications in IBD patients undergoing PCI. Patients with concurrent IBD and PCI were compared to non-IBD controls via multivariable logistic regression. Results: On propensity-score-matching analysis, IBD patients undergoing PCI had a higher prevalence of GI complications, including acute liver failure (Odds ratio (OR) 1.48, 95% confidence interval (CI) 1.13-1.93, p = 0.004), mesenteric ischemia (OR 5.34, 95% CI 1.56-18.40, p = 0.007), and need for blood transfusion (OR 1.74, 95% CI 1.46-2.08, p < 0.001). There was also a higher rate of cardiac complications (OR 1.31, 95% CI 1.05-1.64, p = 0.017). No significant difference in all-cause mortality (OR 0.86, 95% CI 0.72-1.04, p = 0.113) was observed. Conclusions: IBD patients undergoing PCI face increased GI and cardiovascular complications without a significant mortality difference. These findings highlight the complex interplay between systemic inflammation, vascular integrity, and procedural outcomes in IBD patients.
Bhagat U, Banga A, Agrawal A, Kumar P, Arockiam AD, Rosenzveig A, Nasif D, Wassif H, Achkar JP
A Bidirectional Analysis of Inflammatory Bowel Disease and Gout: Epidemiologic Evidence of a Stronger Association in Crohn’s Disease from a Nationwide Cohort Study in South Korea. Biomedicines | 2026-03-09
Background: Inflammatory bowel disease (IBD) and gout are both chronic inflammatory conditions. Emerging evidence suggests a potential link between IBD and gout through shared inflammatory and metabolic pathways; however, epidemiological findings remain limited and inconsistent, and the temporal direction of this association has not been clearly established. Methods: Through the use of the South Korean National Health Insurance database, we conducted a nationwide bidirectional matched cohort study. In Study I, 10,793 patients with IBD were matched 1:4 to controls without IBD. In Study II, 25,624 patients with gout were matched 1:4 to nongout controls. Exact matching was performed on age, sex, income level, and region of residence, followed by propensity score overlap weighting. Overlap-weighted Cox proportional hazards models were employed to measure adjusted hazard ratios (aHRs) for incident gout (Study I) and incident IBD (Study II). Results: In Study I, patients with IBD experienced a greater occurrence of gout than matched controls (28.40 vs. 24.20 per 10,000 person-years). IBD was linked to a higher likelihood of gout (aHR, 1.16; 95% CI, 1.04-1.29). When stratified by subtype, Crohn’s disease (CD) revealed a significant relationship with gout (aHR, 1.25; 95% CI, 1.05-1.48), whereas ulcerative colitis (UC) did not. Notably, the association between IBD (including CD and UC) and gout was consistently significant among participants younger than 45 years. In Study II, gout was not related to an elevated likelihood of IBD (aHR, 1.04; 95% CI, 0.91-1.21) or its subtypes. Conclusions: IBD, particularly CD, was linked to a greater likelihood of gout, especially among younger adults, whereas gout was not associated with subsequent IBD, suggesting an asymmetric association between IBD and gout.
Yoo DM, Lee HJ, Kang HS, Choi HG, Han KM, Kim JH, Bang WJ, Kwon MJ
Extraintestinal Manifestations (6 papers)
On the increased prevalence of myasthenia gravis in patients with inflammatory bowel disease. Arquivos de neuro-psiquiatria | 2026-03-23
Abstract not available.
Gondim FAA, Souza MHLP, Braga LLBC
Beyond numbers: challenges in assessing myasthenia gravis prevalence in inflammatory bowel disease. Arquivos de neuro-psiquiatria | 2026-03-23
Distinct clinicopathological features of IgA nephropathy associated with Crohn’s disease: comparison with ulcerative colitis and non-IBD IgA nephropathy. Clinical and experimental nephrology | 2026-03-23
IgA nephropathy (IgAN) is increasingly recognized as a complication of inflammatory bowel disease (IBD), particularly Crohn’s disease (CD). Recent studies suggest that mucosal immune dysregulation and biologic therapies, particularly tumor necrosis factor (TNF)-α inhibitors, may influence the onset and progression of IgAN in IBD. However, its clinicopathological characteristics in this context remain uncertain. We conducted a retrospective, multicenter study of patients with biopsy-proven IgAN and concurrent CD. Patients with CD-associated IgAN (CD-IgAN) were compared with those with ulcerative colitis-associated IgAN (UC-IgAN) and with IgAN unassociated with IBD (non-IBD-IgAN). Clinical parameters at kidney biopsy, treatment history, and histopathological findings were evaluated. One-year outcomes included changes in proteinuria, hematuria status, and estimated glomerular filtration rate (eGFR). In total, eight patients with CD-IgAN, eight patients with UC-IgAN, and 32 matched non-IBD-IgAN controls were included. Patients with CD-IgAN exhibited lower eGFR, higher serum IgA levels, and a higher prevalence of tubulointerstitial nephritis compared to non-IBD-IgAN controls. Moreover, CD-IgAN was characterized by significantly lower eGFR and a nonsignificant trend toward more advanced tubulointerstitial injury compared to UC-IgAN. The use of TNF-α inhibitors was more frequent in the CD-IgAN group. At 1 year, all groups exhibited reductions in proteinuria, with no significant differences in eGFR change or hematuria resolution. CD-IgAN represents a distinct clinicopathological phenotype characterized by lower kidney function and more severe tubulointerstitial injury. Although causality cannot be inferred, careful kidney monitoring should be considered in patients with CD, particularly those receiving TNF-α inhibitors.
Shimizu A, Tsuboi N, Hatanaka S, Fukunaga S, Sasaki T, Haruhara K, Okabe M, Yokote S, Ueda H, Iwashita Y
Comments on “Increased Prevalence of Pulmonary Diseases in Patients With Inflammatory Bowel Disease: A Retrospective Multicenter Study”. Journal of clinical gastroenterology | 2026-03-23
Microscopic colitis and primary sclerosing cholangitis are bidirectionally associated: A nationwide matched cohort and case-control study. Journal of internal medicine | 2026-03-22
Microscopic colitis (MC) is an inflammatory disease of the colon. Although there is a known association between inflammatory bowel disease (IBD) and primary sclerosing cholangitis (PSC), evidence linking MC and PSC remains scarce. We aimed to investigate the bidirectional association between MC and PSC. Leveraging the nationwide Swedish histopathology cohort Epidemiology Strengthened by histoPathology Reports in Sweden, we conducted a matched cohort study (2002-2023, follow-up until 2024) and a case-control study (1987-2023). Patients with IBD were excluded. Adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) were estimated using Cox regression and adjusted odds ratios (aORs) using conditional logistic regression. The cohort study included 21,340 patients with biopsy-confirmed MC and 101,707 matched reference individuals (matched by age, sex, birth year and county). Over a median follow-up of 7 years, PSC was diagnosed in 21 patients with MC and 15 reference individuals, corresponding to incidence rates of 11.9 (95% CI = 7.8-18.3) and 1.7 (95% CI = 1.0-2.8) per 100,000 person-years, yielding an aHR of 7.17 (95% CI = 3.69-13.9). The case-control study included 22,729 MC cases and 108,467 matched controls. Prior PSC was more frequent among MC cases (19/22,729; 0.08%) than controls (12/108,467; 0.01%), yielding an aOR of 7.26 (95% CI = 3.50-15.1). Our findings remained robust across multiple sensitivity analyses, including sibling-controlled analyses. This nationwide study reveals a bidirectional association between MC and PSC. Although absolute risks are low, these findings suggest that MC may have diagnostic relevance in suspected PSC cases, and vice versa. Physicians treating MC patients should be alert to signs and symptoms of PSC.
Bergman D, Forss A, Sun J, Ebrahimi F, Lindkvist B, Hedin C, Hagström H, Bergquist A, Yao J, Ludvigsson JF
Primary sclerosing cholangitis.Review Lancet (London, England) | 2026-03-20
Primary sclerosing cholangitis is a rare, chronic cholestatic liver disease characterised by biliary inflammation and fibrosis. Inflammatory bowel disease co-occurs in 50-80% of individuals with primary sclerosing cholangitis and there is an increased risk for hepatobiliary and colorectal cancers. Primary sclerosing cholangitis presentation is highly variable but there is usually a slowly progressive fibrosis of the bile ducts with strictures, development of liver fibrosis and cirrhosis, and eventually a need for liver transplantation, after which primary sclerosing cholangitis can reoccur. Primary sclerosing cholangitis is diagnosed mostly at the asymptomatic stage but, as the disease advances, people often have itching, fatigue, upper right abdominal pain, recurrent cholangitis, or complications related to portal hypertension. There are few treatment options and its exact cause and pathogenesis remain unclear. It is widely believed that both genetic and environmental factors are important, with the intestinal microbiome increasingly recognised as crucial to disease development, progression, and outcomes. This Seminar explores the clinical features of primary sclerosing cholangitis, summarises the current understanding of its pathogenesis, and gives insights into the challenges and opportunities in managing the disease.
von Seth E, Karlsen TH, Tanaka A, Ponsioen C, Bergquist A
Quality of Life & PROs (6 papers)
CBP phosphorylation maintains intestinal homeostasis by supporting the stem cell niche through versican. Nature communications | 2026-03-28
CREB-binding protein (CBP) is a transcriptional coactivator, and we reported its phosphorylation regulates cell fate. Impaired CBP phosphorylation alters its binding preference for p53 in CBPAA mice, leading to distal colonic abnormalities. These changes are accompanied by reduced expression of versican, an extracellular matrix component that supports the intestinal stem cell niche, leading to impaired intestinal epithelial cell (IEC) proliferation and organoid formation. Deleting p53 in the IECs of CBPAA mice (CBPAAp53ΔIEC) restores versican expression and reverses the colonic phenotype. Versican replenishment and phosphomimetic CBP mutants rescue versican expression and IEC stemness in CBPAA organoids. Importantly, colonic tissues from ulcerative colitis patients exhibit impaired CBP phosphorylation, increased CBP-p53 binding, decreased versican expression and IEC proliferation, highlighting the clinical relevance of this phenomenon. In this work, we demonstrate CBP phosphorylation safeguards intestinal homeostasis by maintaining the stem cell niche through versican, highlighting versican as a potential therapeutic target for inflammatory bowel disease.
Lin YT, Liu C, Hsu YH, Miaw SC, Wu MS, Chen CC
The SILVER Platter for Patients with Inflammatory Bowel Disease (IBD): An IBD Pharmacy Technician-Led Subcutaneous Biologic Home Delivery Service Is Associated with Sustained Improvement in Adherence and Active Health Management. Digestive diseases and sciences | 2026-03-27
Subcutaneous medications are associated with lower adherence, risking adverse disease outcomes. This project aimed to evaluate the effect of a pharmacy technician-led subcutaneous biologic home delivery (SILVER) service on medication adherence, health literacy, and disease outcomes in patients with inflammatory bowel disease (IBD). Patients treated with a subcutaneous biologic, residing within 45 min of a tertiary IBD service, were offered home delivery of the biologic. Demographic and clinical data were recorded. Telephone interviews at baseline, 6 months, and 12 months were performed to evaluate change in quality of life via Short Inflammatory Bowel Disease Questionnaire (SIBDQ), medication adherence, health literacy via Health Literacy Questionnaire, and electronic Health Literacy Questionnaire (HLQ & eHLQ) and clinical disease activity. Eighty patients were included. 45 (56.3%) patients were treated with ustekinumab, 23 (28.8%) with adalimumab, 11 (13.8%) with subcutaneous infliximab and 1 (1.2%) with subcutaneous vedolizumab. Significant improvement (p ≤ 0.05) was observed at 6 and 12 months in SIBDQ, adherence, and HLQ/eHLQ (two domains), and fecal calprotectin at 6 months. Of these patients, 43 were treated with the same biologic agent and route for at least 6 months prior to enrollment. In this subgroup, significant improvement (p ≤ 0.05) was measured at 6 and 12 months in SIBDQ, adherence, and HLQ/eHLQ (one domain). A novel pharmacy technician-led subcutaneous biologic home delivery service was associated with improvement in IBD-related quality of life, medication adherence, health literacy, and disease outcomes, sustained to 12 months. Larger studies are warranted to evaluate home delivery of subcutaneous biologics in IBD.
Leake A, Bishara M, Lo SW, Tacey M, Rajendran M, Lucas S, Chauhan A, Dalgleish N, Sepe G, Tsoi A
Promoting Self-Care in Individuals with Inflammatory Bowel Disease: A Scoping Review.Review Journal of gastrointestinal and liver diseases : JGLD | 2026-03-27
Self-care has emerged as a pivotal component in the long-term management of inflammatory bowel disease, yet the literature remains fragmented regarding educational interventions supporting its implementation. This scoping review aims to systematically map existing educational strategies designed to promote self-care among individuals with inflammatory bowel disease and to identify barriers, facilitators, and implications for nursing practice. Following the Joanna Briggs Institute methodology, a scoping review was conducted across five electronic databases (PubMed, Embase, CINAHL, Web of Science, and Scopus) with no date restrictions. Eligible studies focused on educational interventions targeting at least one of the following dimensions of self-care: maintenance, monitoring, or management. Data extraction and synthesis were guided by a theoretical model of self-care. Findings were narratively synthesized and supported by summary tables and conceptual mapping. Fourteen studies published over the past seventeen years were included. Interventions ranged from cognitive-behavioral therapy and digital health tools to structured group education programs. Most were implemented in high-income countries and delivered by multidisciplinary teams. Key barriers included time constraints, limited financial and human resources, and patient reluctance to adopt active roles. Facilitators encompassed the use of smartphone applications, teach-back methods, and communication tools such as patient passports. Reported outcomes included improvements in treatment adherence, psychological well-being, and patient engagement. Educational interventions, particularly when grounded in self-care theory and delivered by nursing professionals, can enhance autonomy and quality of life in individuals with inflammatory bowel disease. Future programs should emphasize personalization, inclusiveness, and long-term behavioral change, supported by robust evidence and sustainable implementation models.
Milani I, Napolitano D, Petralito M, Capatti SR, Gennari E, Amato S, Di Cosimo V, Petruccini G, Orgiana N, Bozzetti M
Dietary inflammatory index and objective disease activity in IBD: no association found. European journal of clinical nutrition | 2026-03-23
Inflammatory Bowel Disease (IBD) involves genetic and environmental factors, but the relationship between disease activity, adiposity, and diet remains unclear. To investigate the association between endoscopic/radiological activity of IBD, body adiposity, and the Dietary Inflammatory Index with or without adjustment for energy density (E-DII or DII). An observational, cross-sectional study was carried out. Endoscopic activity was defined by an endoscopic Mayo score >2, Crohn’s Disease Endoscopic Index of Severity (CDEIS) > 5, and/or the presence of a deep ulcer in any intestinal segment. Body adiposity was estimated using the body mass index, waist circumference, and waist-hip ratio (WHR). The DII and E-DII scores were calculated from a validated quantitative food frequency questionnaire. According to the DII and E-DII, the patients were divided into three groups: the first with the least pro-inflammatory diet and the third with a predominantly pro-inflammatory diet. Of the 62 patients, 58.1% (n = 36) were in remission (RD) and 41.9% (n = 26) had active disease (AD). The proportion of patients with overweight/obesity was 69.4% (n = 25) in the RD group and 50.0% (n = 13) in the AD group. Patients in remission exhibited significantly higher WHR (p < 0.05) and a greater frequency of central obesity (p < 0.01). A predominantly pro-inflammatory diet was common across both groups; 58.3% (n = 21) of RD patients and 50.0% (n = 13) of AD patients were in the highest DII tertile. Similar results were found for the E-DII. Among patients with IBD, pro-inflammatory dietary patterns and excess adiposity are highly prevalent. Despite greater central adiposity in patients in remission, no significant associations were found between DII or EDII scores and endoscopic and radiological markers of disease activity.
de Oliveira RMV, Vasques ACJ, Romero SA, Shivappa N, Wirth MD, Hébert JR, Reis GFSR, Nagasako CK
The Impact of Informal Caregiving on Patient-Reported Outcomes, Psychological Well-Being and Quality of Life in Inflammatory Bowel Disease: A Systematic Review.Review Nursing reports (Pavia, Italy) | 2026-03-13
Background/Objectives: While caregiver burden in Inflammatory Bowel Disease (IBD) is well documented, the association between informal support and patient-reported outcomes (PROs), particularly health-related quality of life (QoL) and psychological well-being, remains underexplored. This systematic review synthesizes evidence on the association of informal caregiving on patient-reported QoL and psychosocial outcomes and maps the available evidence on clinical outcomes. Methods: Following international reporting guidelines and prospective protocol registration, a systematic search was conducted across five electronic databases between May and October 2025. Observational studies in adults with IBD assessing informal support and patient-reported or psychosocial outcomes were included. Owing to substantial heterogeneity in constructs and outcome measures, results were synthesised using a structured Synthesis Without Meta-analysis (SWiM) approach. Methodological quality was assessed using standardised critical appraisal checklists. Results: Six cross-sectional studies involving 1036 patients and 417 informal caregivers met the inclusion criteria. All studies reported a positive direction of association between higher levels or better quality of informal caregiver support and improved patient-reported QoL. Several studies identified psychological and relational factors, such as lower patient psychological distress and caregiver-related positive feelings and caring ability, as mechanisms statistically associated with this relationship. Conclusions: Available cross-sectional evidence suggests a positive association between informal support and patient-reported QoL/psychological outcomes in IBD, but causality cannot be inferred. Priorities include longitudinal dyadic studies and caregiver-inclusive interventions, alongside standardised definitions and measures of support.
Benedetti F, Imperatori G, Amatucci V, Lo Cascio A, Amato S, Napolitano D
The IBD-FITT Study-Moderate-Intensity Exercise for Patients with Active Inflammatory Bowel Disease: An Open-Label Randomized Controlled Trial. Journal of clinical medicine | 2026-03-10
Background: Exercise has been suggested as a supplementary modality for Inflammatory Bowel Disease (IBD), but supporting evidence remains scarce. We aimed to assess whether a 12-week physical exercise intervention improves quality of life (QOL) in adults with active IBD. Methods: An open-labeled randomized controlled trial examining the efficacy of a 12-week physical exercise intervention on QOL in adults (18-65 years) with active IBD. Participants were randomized 1:1 into either an intervention group, with two weekly supervised exercise sessions and one home session, or a control group with standard care. QOL by the Inflammatory Bowel Disease Questionnaire (IBDQ) was the primary outcome. Secondary outcomes were the European Quality of Life 5 Dimensions (EQ5D), waist circumference, blood pressure, disease activity, and lipid status. Explorative outcomes were C-reactive protein, fecal calprotectin, and cytokines (interleukin-6, -8, and -10 and tumor necrosis factor). Results: We screened 183 patients and included 44 participants, with 22 in each group. Eleven participants completed more than 50% of the exercise sessions. Among the participants, 17 were male, 27 were female, and the mean age was 37 years. The mean IBDQ scores at week 12 showed no statistically significant difference: 172 for the intervention group (95%CI: 158-185) and 164 for the control group (95%CI: 151-178). No clinically significant differences for secondary or exploratory outcomes were found. Conclusions: We did not find any difference in the QOL after a 12-week exercise intervention in patients with active IBD compared to standard care. Recruiting proved difficult, as did adherence to exercise sessions, mostly due to scheduling issues.
Lund K, Knudsen T, Kjeldsen J, Lambertsen KL, Nielsen RG, Juhl CB, Nørgård BM
Endoscopy & Imaging (non-IUS) (5 papers)
Association between index adenomas and advanced findings at third colonoscopy: Data from the New Hampshire Colonoscopy Registry. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association | 2026-03-27
The United States Multi-Society Task Force for Colorectal Cancer (CRC) provides recommendations for the 2nd surveillance colonoscopy for patients with adenomas on index exam. However, evidence which informs risk at second surveillance is limited due to lack of data on quality measures and known risk factors. We evaluated the risk for an advanced outcome on 2nd surveillance colonoscopy for patients with index adenomas and a 1st surveillance colonoscopy without polyps, while accounting for risk factors and adenoma detection rates. Our primary outcome was the detection of advanced outcomes at 2nd surveillance colonoscopy as defined by (large (>1cm)/dysplastic serrated polyps (SP), advanced adenoma (AA), or CRC. Another outcome was AA or CRC. We used prospectively collected New Hampshire Colonoscopy Registry (NHCR) data. Patients had two surveillance colonoscopies >12 months apart and a first surveillance colonoscopy without polyps. Patients had no previous colorectal neoplasia, genetic syndromes, or inflammatory bowel disease. Patients were risk-stratified based on index colonoscopy findings; no adenomas; 1-2 non-advanced adenomas; 3-4 non-advanced adenomas; AA /5+ non-advanced adenomas. The reference group had no adenomas on index and 1st surveillance. Covariates in the Poisson model included family history of CRC, smoking, adenoma detection rates, and serrated polyps on index exam. We included 3171 NHCR patients. 3.7%(95%CI: 3.0%-4.6%) of patients with no index adenomas, 6.3%(4.9-8.2) with 1-2 index non-advanced adenomas, 4.3%(1.5-12.0) with 3-4 index non-advanced adenomas, and 6.2%(4.0-9.4) with 5+ non-advanced adenomas and/or advanced adenomas developed advanced outcomes on 2nd surveillance colonoscopy. The adjusted rate ratio for advanced outcomes on 2nd surveillance exam was 2.12(95%CI:1.06- 4.25) in patients with AA/5+ non-advanced adenomas, 1.23(95%CI:0.26-5.74) in patients with 3-4 non-advanced adenomas, and 1.67(95%CI:1.01-2.74) in patients with 1-2 non-advanced adenomas. The adjusted rate ratio for AA or CRC on 2nd surveillance exam was 3.47(95%CI:1.46- 8.24) in patients with AA/5+ non-advanced adenomas, 2.26(95%CI:0.48-10.67) in patients with 3-4 non-advanced adenomas, and 1.84(95%CI:0.94-3.59) in patients with 1-2 non-advanced adenomas. Our analysis demonstrated that patients with advanced adenomas or 5+ adenomas on index exam and a normal 1st surveillance exam have increased risk for advanced findings on second surveillance colonoscopy. This association is independent of quality measures including ADR and known risk factors such as smoking and BMI.
Javidi D, Dairi O, MacKenzie TA, Amos CI, Butterly LF, Anderson JC
Use of magnetically controlled capsule endoscopy in inflammatory pediatric Crohn’s disease. Journal of pediatric gastroenterology and nutrition | 2026-03-26
This study aimed to evaluate the clinical utility of magnetically controlled capsule endoscopy (MCCE) in the evaluation and management of pediatric Crohn’s disease (CD). A single-center retrospective cohort study was conducted on pediatric CD patients diagnosed at Shanghai Children’s Hospital between October 2020 and September 2024. Clinical data, procedure completion rates, and laboratory parameters were collected. The Lewis score was applied to quantify small bowel mucosal inflammation, and correlations with the Pediatric Crohn’s Disease Activity Index (PCDAI), hematologic parameters, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), inflammatory cytokines, gastric transit time (GTT), small bowel transit time (SBTT), and bowel wall thickness (BWT) were examined. Multivariate linear regression was performed to identify independent predictors of the Lewis score. Twenty-four children underwent 66 MCCE examinations. The detection rate of small bowel lesions reached 96.6%, with mucosal edema and ulceration as the predominant findings, while polypoid hyperplasia (6.8%) and active bleeding (3.4%) were less common. The Lewis score showed significant correlations with PCDAI, CRP, ESR, interleukin-12p70 (IL-12p70), white blood cell count (WBC), hemoglobin (Hb), and platelet count (PLT), but no significant associations with mean corpuscular volume (MCV), neutrophil count (NEUT#), fecal calprotectin (FC), tumor necrosis factor-α (TNF-α), GTT, SBTT, or BWT. Multivariate analysis identified IL-12p70 and PCDAI as independent predictors of the Lewis score. No serious adverse events occurred. MCCE is feasible and effective for assessing small bowel and upper gastrointestinal involvement in pediatric CD. Elevated Lewis scores may reflect increased mucosal inflammation and aid in disease assessment.
Li Y, Cheng W, Wang L, Feng Y, Wang X, Gu Z, Liu H
The prognostic role of magnetic resonance enterography at diagnosis in paediatric isolated ileocaecal Crohn’s disease. Journal of pediatric gastroenterology and nutrition | 2026-03-25
We aimed at identifying magnetic resonance enterography (MRE) predictors of surgical intervention and anti-tumor necrosis factor alpha (TNF-α) initiation in a paediatric cohort of patients newly diagnosed with isolated ileocaecal (L1) Crohn’s disease (CD). A longitudinal retrospective study was conducted at two Italian paediatric referral centres (‘Meyer Children’s Hospital’, Florence and ‘Maggiore Hospital’, Bologna). We collected data from L1 CD patients who underwent MRE at diagnosis between January 2011 and December 2022, with a minimum follow-up of 2 years. Univariate and multivariate Cox-regression analyses were performed to investigate MRE predictors for the outcomes over time. Thirty-four out of 383 (8.9%) CD paediatric patients met the inclusion criteria. Fifty per cent were male; median age at diagnosis was 14.1 years (interquartile range [IQR] 11.8-15.1 years). Ten patients (29.4%) underwent surgery, and 17/34 (50%) needed treatment escalation to anti-TNF-α during a median follow-up of 4.5 years (Q1-Q3 2.4-6.6 years). Maximum bowel wall thickness (BWT) was the only MRE parameter independently associated with surgery (hazard ratio [HR] 1.54, 95% confidence interval [CI] 1.02-2.37, p = 0.04) and anti-TNF-α initiation (HR 1.56, 95% CI 1.1-2.22, p = 0.01) over time. BWT > 8 mm was the optimal cut-off to identify patients who required surgery (sensitivity 78%, specificity 52%, area-under-the-curve 0.73, 95% CI 0.54-0.92, p = 0.026). BWT assessed at MRE performed at diagnosis was an independent predictor of surgery and treatment escalation over time in a paediatric cohort with L1 CD. BWT > 8 mm was the optimal cut-off to identify patients at higher risk for surgery.
Pochesci S, Scarallo L, Rubera F, Pranzetti A, Di Maurizio M, Basile M, Orlandi PE, Alvisi P, Lionetti P
Comparison of endoscopy and mobile health index for ulcerative colitis. Scandinavian journal of gastroenterology | 2026-03-25
At Haukeland University Hospital, the Mobile Health Index for Ulcerative Colitis (MHI-UC), a patient-reported outcome measure (PROM), is used in the outpatient clinic to detect disease activity in patients. The primary objective of the study was to compare the MHI-UC with the endoscopic Mayo score (e-MAYO) in a Norwegian cohort, and to investigate the impact on treatment decisions and response. The study is single-center and retrospective. Patients were identified by searching patient journals and screened for participation. Patients who had answered the MHI-UC within ±4 weeks of endoscopy, with no change in treatment, were eligible. Clinical intervention involved treatment changes or referrals to endoscopy or cross-sectional imaging. For those with multiple endoscopies, data from all were collected. Response was defined as a change in e-MAYO score of 1 or more. The MHI-UC correlated with endoscopic activity scored by e-MAYO (r = 0.64, p < 0.001). The AUROC for detecting endoscopic disease activity was 0.92 for e-MAYO > 1 and 0.78 for e-MAYO > 0. Patients receiving a clinical intervention (4.3 ± 3.5 vs 2.3 ± 2.7, p = 0.001) or with a change in e-MAYO (3.9 ± 2.7 points vs 0.7 ± 2.8 points) had a significantly higher MHI-UC compared to those without need for intervention. The MHI-UC corresponds well with the endoscopic evaluation in patients with UC. The MHI-UC can be used to detect moderate to severe disease activity in UC with high accuracy and to detect changes in endoscopic activity.
Sommervoll FÅ, Songstad MME, von Volkmann HL, Nylund K
Diagnostic value of CT enterography combined with inflammatory indicators in active Crohn’s disease. BMC gastroenterology | 2026-03-24
Nutrition & Lifestyle (5 papers)
Micro- and Nanoplastics in the Human Intestine: a Review of Health Implications and Possible Dietary Interventions.Review Advances in nutrition (Bethesda, Md.) | 2026-03-26
Micro- and nanoplastics (MNPs) have emerged as pervasive dietary contaminants, yet their implications for human health remain poorly defined. This review synthesizes current evidence on MNP interactions with the gastrointestinal system, emphasizing barrier disruption, biotransformation, particle uptake, and gut microbiota dysbiosis. Experimental data indicate that particle size, polymer type, and surface properties critically influence intestinal uptake and toxicity, with smaller particles showing greater systemic translocation. Although human evidence is limited and methodologies lack standardization, preliminary associations link MNP exposure with inflammatory bowel disease and metabolic disturbances. Beyond risks, we highlight the role of dietary patterns in modulating exposure and effects: minimizing processed, packaged foods and enhancing fiber, antioxidants, and probiotics may reduce intestinal burden and mitigate oxidative and inflammatory responses. Bridging mechanistic insights with dietary strategies, this review underscores the urgent need for standardized detection methods, human cohort studies, and sustainable food system interventions. STATEMENT OF SIGNIFICANCE: This review uniquely integrates mechanistic toxicology of dietary micro- and nanoplastics with actionable nutritional strategies, providing the first concise synthesis that links intestinal biology and particle toxicodynamics to specific dietary interventions (e.g., fiber, antioxidants, probiotics) and food-system measures aimed at reducing exposure and harm.
Dávalos A, Martín-Santiago V, López de Las Hazas MC
Food as Friend or Foe: A Decadal Narrative Review of Dietary Patterns as Determinants of Gastrointestinal Pathophysiology and Clinical Outcomes (2015-2025).Review International journal of molecular sciences | 2026-03-20
Diet is a major modifiable determinant of gastrointestinal (GI) health, influencing disease risk and progression through coordinated effects on the gut microbiome, immune regulation, epithelial barrier integrity, oxidative balance, and epigenetic mechanisms. This narrative review synthesizes epidemiological, mechanistic, and clinical evidence from the past decade to examine bidirectional relationships between dietary patterns and seven common GI disorders: celiac disease, irritable bowel syndrome (IBS), Crohn’s disease, ulcerative colitis, Helicobacter pylori-associated gastritis, peptic ulcer disease, and lactose intolerance. Western dietary patterns, characterized by high intake of ultra-processed foods and saturated fats and low fiber consumption, are consistently associated with microbial dysbiosis, impaired barrier function, and enhanced inflammatory signaling. In contrast, Mediterranean and plant-forward dietary patterns show protective associations across multiple GI conditions. Mechanistically, diet influences GI pathophysiology largely through microbiome-derived metabolites, particularly short-chain fatty acids, which regulate epithelial homeostasis, immune tolerance, and inflammatory pathways. Condition-specific dietary strategies remain clinically important. Gluten exclusion is essential in celiac disease, low- fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) approaches provide evidence-based symptom control in IBS, and exclusive enteral nutrition or targeted exclusion diets support remission induction in Crohn’s disease. Selected probiotics and emerging postbiotics may provide adjunctive benefits in specific contexts. Despite growing evidence, dietary research remains limited by methodological heterogeneity and interindividual variability. Precision nutrition approaches integrating microbiome profiling and artificial intelligence represent a promising translational direction. Overall, dietary patterns-rather than isolated nutrients-form the foundation of GI dietary therapy.
Moleriu LC, Lupusoru R, Marin RC, Muntean C, Piroș T, Vlad DC, Dumitrașcu AL, Dumitrașcu V
Usefulness of Nutritional Intervention Through New Digital Technologies in Patients with Inflammatory Bowel Disease. Nutrients | 2026-03-13
Background: Malnutrition and suboptimal diet quality are common, yet under-recognized, in inflammatory bowel disease (IBD) and are associated with worse clinical outcomes and lower quality of life. Digital tools may facilitate continuous, personalized nutritional support, but evidence in IBD remains limited. The aim of this study was to evaluate the impact of a nutritional intervention based on a mobile application (Nootric®) on nutritional status, diet quality, and malnutrition risk in patients with IBD undergoing stable follow-up. Methods: We conducted a prospective longitudinal cohort study without a control group including 151 adult patients with Crohn’s disease or ulcerative colitis under stable follow-up in a tertiary IBD unit. Participants used a structured digital nutritional support program through the Nootric® app for 24 weeks, supervised by dietitians and the IBD team. Clinical activity, biochemical markers (C-reactive protein, fecal calprotectin), nutritional biomarkers (albumin, prealbumin, micronutrients), body mass index (BMI), malnutrition risk (self-administered Malnutrition Universal Screening Tool, MUST), and diet quality (PREDIMED and an expanded “Nootric score”) were assessed at baseline, 12 weeks, and 24 weeks. Analyses focused on patients with adequate adherence. Results: Of the 151 included IBD patients, 110 maintained stable app use. Mean albumin increased from 4.38 to 4.49 g/dL at 24 weeks (p = 0.003), and prealbumin from 24.9 to 26.1 mg/dL (p = 0.047), despite the absence of overt protein-calorie malnutrition at baseline. Patients with obesity achieved a mean weight loss of approximately 6% of baseline body weight. Diet quality improved significantly, with higher Nootric score and a positive correlation between app use intensity and increased score. Malnutrition risk according to the MUST scale improved in more adherent patients, while clinical and biochemical disease activity remained stable overall. Conclusions: A mobile app-based nutritional program supervised by dietitians was feasible, well accepted, and associated with improved nutritional markers, diet quality, and malnutrition risk, supporting its role as a complementary component of IBD care.
Suárez Ferrer C, Martorell Mariné I, Rueda García JL, Cubillo García C, García Ramírez L, Amiama Roig C, Sánchez Azofra M, Poza Cordon J, Martin Arranz E, García-Rojas Pleite C
Identification of Ellagic Acid as a Natural GPR35 Agonist for Ulcerative Colitis Therapy. Biomolecules | 2026-03-13
The escalating global burden of Ulcerative Colitis (UC) underscores the urgent need for novel therapeutic strategies. Although dietary modulation is known to influence UC progression, the specific molecular mediators remain largely undefined. Recently, the G protein coupled receptor 35 (GPR35) has emerged as a promising target for maintaining gut homeostasis and promoting intestinal epithelium repair. Yet, whether the therapeutic benefits of dietary polyphenols are mediated through the direct activation of GPR35 remains unexplored. Here, the NanoLuc Binary Technology (NanoBiT) assay was first used to identify the potential GPR35 agonist from a library of 30 natural polyphenolic compounds. We discovered Ellagic acid (EA), a natural polyphenol abundant in fruits and nuts, as the potent GPR35 agonist owing to its most potent agonistic effect. The dose-dependent effect was further confirmed by both NanoBiT and Bret assay. Then, the binding site of the ligand-receptor complex was predicted via molecular docking, and key interactions were validated by site-directed mutagenesis. The results indicated the key binding site of the complex was Gln93, Arg100, Arg151, Phe163 and Ser262. And the conformation of the complex was verified stable by the molecular dynamics simulation. The bioactivity of EA was then evaluated in vivo. And the in vivo experiment indicated that EA alleviated the symptoms of UC. In addition, complementary in vitro assays, including a wound healing (scratch) assay and an SRB proliferation assay, were employed to investigate its effect on intestinal epithelial repair. The in vitro experiment demonstrated that EA enhanced the migration and proliferation of human colonic epithelial cells, an effect that was specifically abolished by the GPR35 antagonist CID2745687, indicating the key role GPR35 played in the intestinal repair. Collectively, our study demonstrates that the natural polyphenolic compound EA promotes epithelial healing and ameliorates colitis by acting as a GPR35 agonist.
Liu H, Yang L, Ma X, Wang G, Wang D, Liu X, Li Z, Guo D
Metabolic Disorders and Inflammatory Bowel Diseases: Unraveling Shared Pathways and Clinical Interactions.Review Metabolites | 2026-03-09
Inflammatory bowel diseases (IBDs) and metabolic disorders are increasingly recognized as interconnected conditions that frequently coexist and influence each other’s clinical course. Accumulating evidence indicates that patients with IBD face a substantial burden of obesity, metabolic syndrome, metabolic dysfunction-associated steatotic liver disease, osteoporosis, and type 2 diabetes. These associations appear to be driven by shared and interacting mechanisms, including intestinal barrier disruption, gut microbiota dysbiosis, chronic systemic inflammation, and adipose tissue-mediated immunometabolic pathways. Metabolic comorbidities may worsen IBD activity, reduce response to therapy, increase complications, and contribute to higher health care utilization. Conversely, intestinal inflammation and commonly used treatments, particularly corticosteroids, can adversely affect glucose metabolism, lipid metabolism, body composition and bone homeostasis. Advanced therapies have demonstrated variable metabolic effects, some of which may be beneficial through suppression of systemic inflammation. Recognition of these bidirectional interactions highlights the importance of routine metabolic screening and integrated, multidisciplinary management. Lifestyle interventions, nutritional optimization and individualized therapeutic strategies represent central parts of comprehensive management.
Fousekis F, Lamprou A, Saridi M, Mastorogianni IN, Mpakogiannis K, Lianos GD, Katsanos KH
Guidelines & Consensus (4 papers)
Factors associated with urgent consultation recommendations for patients with inflammatory bowel disease calling a telephone service about worsening symptoms: a secondary analysis. BMC gastroenterology | 2026-03-27
Abstract not available.
Kawakami A, Tanaka M, Sakagami K, Ito H
Defining Moderate Disease Activity and Severity in Crohn’s Disease and Ulcerative Colitis. Journal of clinical gastroenterology | 2026-03-24
This research aimed to review the literature for definitions of moderate Crohn’s disease (CD) and ulcerative colitis (UC). Real-world evidence suggests that biologics may achieve better outcomes in patients with moderate disease than with severe disease; however, research has been hindered by the lack of consensus on the definition of moderate disease. We conducted a systematic literature review (SLR) of observational and interventional studies published from 2015 onwards, followed by a targeted literature review (TLR) of phase 3 trials of pharmacological therapies from 2000 onwards, to identify definitions of disease severity. A consensus meeting was convened for experts to discuss how to distinguish moderate from mild or severe disease in clinical practice. The SLR and TLR included 140 and 101 publications, respectively. Six definitions of moderate CD were identified from 7 publications and 16 definitions of moderate UC from 23 publications. Most definitions were based on Crohn’s Disease Activity Index (CDAI) or Mayo score (for UC). Three publications defined moderate CD as CDAI of 200 to 450, 220 to 450, or ≤330. Moderate UC was mostly defined as a Mayo score of 6 to 10 but there was overlap with the range used for severe UC. No definition of moderate disease encompassed quality of life or disease course and prognosis, which were considered important by experts in assessments of disease severity in clinical practice. A comprehensive and clinically relevant definition of moderate disease is needed to identify patients with CD or UC who can benefit from biologics.
Chou C, Sanchirico M, Mukherjee RS, Hudesman D, Ritter TE, Dulai PS
[Use of NSAIDs in inflammatory bowel disease].Systematic review Lakartidningen | 2026-03-24
Health Technology Assessment (HTA) Region Stockholm conducted a systematic review evaluating the risk of flare-ups from use of non-steroidal anti-inflammatory drugs (NSAID) in patients with inflammatory bowel disease (IBD). Patients with IBD, such as ulcerative colitis and Crohn’s disease, often experience pain including joint pain, pain from kidney stones, menstrual pain, and headache. Effective pain management is crucial for maintaining daily function and quality of life. There are concerns that NSAIDs may increase the risk of IBD flare-ups, and international guidelines vary in their recommendations. The overview indicates that short-term NSAID use is likely associated with a minimal or negligible increase in risk among patients with well-controlled IBD in remission. The findings are however uncertain due to limited data and methodological limitations in the included studies.
Dharmadasa V, Kapraali M, Peira N, Vitols S
[Guideline for the Treatment of Ulcerative Colitis and Crohn’s Disease in Adult Patients].Systematic review Revista medica de Chile | 2026-03-12
Ulcerative colitis and Crohn’s disease are chronic conditions that can take a potentially severe or even life-threatening course, with high morbidity stemming from their complications. These diseases affect not only physical health but also significantly impact the quality of life of patients and their families. The primary goal of these guidelines is to provide treating physicians with clear, up-to-date information regarding the quality and strength of evidence supporting each therapeutic option. The document is intended to support shared clinical decision-making, empowering healthcare providers and patients to jointly develop a personalized treatment plan tailored to individual needs, preferences, and clinical characteristics. Although epidemio-logical data on inflammatory bowel disease (IBD) in Latin America remain limited, multiple studies have highlighted a substantial disease burden across the region, along with ongoing challenges in diagnosis, access to advanced therapies, and long-term management. In response to these needs -and recognizing the continuous advances in therapeutic strategies- the Chilean Working Group on Crohn’s Disease and Ulcerative Colitis (ACTECCU) undertook the development of clinical guidelines aimed at the treatment of IBD in adult patients. The guideline was developed through a systematic review of the best available evidence, enriched by the active participation of a national panel of specialists who contributed their clinical expertise in the comprehensive management of IBD. Ultimately, these guidelines aim to optimize the management of IBD in Chile, promote more equitable access to evidence-based treatments, and improve health outcomes and quality of life for those living with these chronic conditions.
Núñez F P, Alfaro I, Pavez C, Pizarro G, Estay C, Sepúlveda R, Arenas A, Quera R, Slimming J, Candia R
AI & Machine Learning (2 papers)
Univariate- and machine learning-based plasma metabolite signature differentiates PSC-IBD from IBD and is predicted to be driven by gut microbial changes. Metabolomics : Official journal of the Metabolomic Society | 2026-03-28
Inflammatory bowel disease (IBD) is a group of chronic inflammatory conditions of the gastrointestinal tract comprising two major phenotypes, Crohn’s disease (CD) and ulcerative colitis (UC). Up to 8% of patients with IBD also develop primary sclerosing cholangitis (PSC), characterised by cholestasis and progressive destruction of the biliary tree, resulting in cirrhosis, end-stage liver disease and cholangiocarcinoma. Clinical outcome can currently not be improved through medication, denoting the importance of diagnosis prior to irreversible damage, which requires biomarkers of (early) disease. We employed direct infusion mass spectrometry (DI-MS)-based metabolomics on plasma to build predictive, potentially diagnostic models for PSC-IBC and other phenotypes including IBD subtype, stricture and fistula presence and more. We used this dataset to simultaneously investigate aetiology of these phenotypes. Samples of 348 IBD patients were included for analysis. The data was analysed using our previously reported tool, MetaboShiny. We built predictive models using Random Forest (RF), and subsequently combined with univariate statistics to rank m/z features connected to PSC-IBD. This ranking was used to perform mummichog enrichment analysis connected to metabolic and metagenomic changes. The highest performing predictive model differentiated PSC-IBD from PSC. The metabolic signature was enriched in changes to amino acid and vitamin metabolism, alongside changes to the metagenome suggesting decreases in anti-inflammatory microbial species and increases in pro-inflammatory species. These results demonstrate the potential of DI-MS-based metabolomics with machine learning to create diagnostic models and generate hypotheses on the metabolomic-metagenomic level. Sharing our dataset of patients will enrich future human IBD metabolomics research possibilities.
Wolthuis JC, Schultheiss JPD, Magnúsdóttir S, Stigter E, Tang YF, Jans J, Oldenburg B, de Ridder J, van Mil S
A lactylation modification-related prediction model for the diagnosis of ulcerative colitis based on machine learning. Frontiers in immunology | 2026-03-11
Lactylation modification serves as a critical link between metabolic reprogramming and epigenetic regulation, playing a significant role in the progression of both malignant tumors and inflammatory diseases. Nevertheless, its specific function in the pathogenesis of ulcerative colitis (UC) remains poorly understood. The hub genes associated with lactylation in UC were identified and validated by mining three UC-related datasets (GSE206285, GSE75214, and GSE87466) from the GEO database, and we created a lactylation-related prediction model for the diagnosis of UC. The lactylation levels of different immune cells were also investigated via single-cell (sc) RNA-sequencing data. Finally, the core genes of lactylation were validated in vitro. Four lactylation-related core genes (HIF1A, SLC25A12, SLC16A3, and PFKFB2) that are closely correlated with UC were identified by three machine learning methods, and the lactylation-related prediction model based on the four genes exhibited outstanding diagnostic performance for UC (AUC:0.976, 95% CI: 0.941-1.00). scRNA-sequencing analysis revealed that HSC, NK, and macrophage cells exhibited higher lactylation-related scores in UC compared to other immune cells. After Nala intervention, the expressions of the four core genes were significantly increased, while the expressions of the four genes were significantly decreased after treatment with 2-DG. By applying machine learning methods to analyze sequencing data, we identified core lactylation-related genes in UC and developed a diagnostic model with high predictive performance. Furthermore, based on scRNA-seq data, we investigated lactylation modifications across seven types of immune cells in UC patients, providing valuable insights into the interplay between lactylation and immune cells in UC.
Liu J, Kang X, Zhou Y, Li J
Genetics & Genomics (2 papers)
ORMDL3: from an asthma susceptibility gene to multi-disease associations.Review Frontiers in genetics | 2026-03-18
The ORMDL3 protein, encoded by the ORMDL3 gene, functions as a transmembrane protein in the endoplasmic reticulum. Initially identified through its genetic link to asthma susceptibility, ORMDL3 plays a key role in regulating sphingolipid metabolism by inhibiting Serine Palmitoyltransferase activity. This regulation influences the synthesis of bioactive lipids like ceramides, which in turn affect cellular homeostasis, inflammatory responses, and immune regulation. Recent studies show that ORMDL3’s function extends beyond the respiratory system, with involvement in obesity, diabetes, atherosclerosis, inflammatory bowel disease, autoimmune diseases, and various cancers. It regulates processes such as endoplasmic reticulum stress, the unfolded protein response, autophagy, calcium signaling, and inflammatory pathways. This review highlights ORMDL3’s expression patterns, molecular mechanisms, and clinical relevance across different diseases, emphasizing its role as a biological node linking multiple pathologies. Additionally, it discusses ORMDL3’s potential as a target for innovative therapies and diagnostic biomarkers, laying the groundwork for future interdisciplinary research and precision medicine applications.
Han Z, Guo S, Wang C, Niu Y, Liu J, Li K, Li D, Yu F, Li X
Endarachne binghamiae Extract Alleviates Colitis by Suppressing NLRP3 Inflammasome Activation via Regulation of NOX-iNOS Crosstalk. International journal of molecular sciences | 2026-03-14
Inflammatory bowel disease (IBD) is triggered by genetic predisposition and chronic inflammation, with aberrant activation of the innate immune complex NLRP3 inflammasome playing a pivotal role in its pathogenesis. In this study, we investigated the effects of a hot water extract from the brown alga Endarachne binghamiae (EB-WE) on the inhibition of NLRP3 inflammasome activation, with a focus on its antioxidant properties, in various inflammation models. In bone marrow-derived macrophages (BMDMs), NLRP3 inflammasome activation was induced using LPS and ATP, and EB-WE pretreatment (100, 200 µg/mL) significantly reduced the secretion of IL-1β and IL-18. Confocal immunofluorescence analysis further confirmed that EB-WE suppressed the formation of the NLRP3-ASC/caspase-1 complex. Furthermore, the in vivo anti-IBD efficacy of EB-WE was assessed using a DSS-induced mouse model, in which colonic inflammation and NLRP3-mediated responses were prominent. Oral administration of EB-WE (2 or 5 mg/day) markedly ameliorated clinical symptoms, such as weight loss, diarrhea, and rectal bleeding, and significantly reduced the disease activity index (DAI). EB-WE also decreased serum pro-inflammatory cytokine levels and the expression of NLRP3 inflammasome-related molecules in colon tissue at both the gene and protein levels. In both BMDMs and the IBD mouse model, we further analyzed the upstream regulatory pathway involving NOX2-iNOS. EB-WE efficiently inhibited the activation of the NOX-iNOS axis and NF-κB phosphorylation, thereby alleviating inflammasome activation associated with DSS-induced oxidative stress and neutrophil/macrophage infiltration. Collectively, these results demonstrate that EB-WE effectively suppresses the formation and activation of the NLRP3 inflammasome by modulating the NOX-iNOS axis and the NF-κB pathway via antioxidant mechanisms. These findings suggest that EB-WE holds promise as a novel marine-derived natural therapeutic agent for the treatment of chronic inflammatory diseases.
Lee SS, Lee SH, Kim SY, Lee BH, Yoo YC
IBD-associated Neoplasia (2 papers)
Safety of Venous Thromboembolism Pharmacological Prophylaxis in Hospitalized Patients With Inflammatory Bowel Disease (VISCOUS Study). Journal of patient safety | 2026-03-26
Hospitalization secondary to inflammatory bowel disease (IBD) exacerbation is a significant risk factor for venous thromboembolism (VTE). Guidelines recommend the use of thromboprophylaxis; however, the risk of bleeding is unknown. We therefore aimed to evaluate the safety of pharmacological thromboprophylaxis in hospitalized patients with IBD. This was a retrospective cohort study. IBD patients’ electronic health records were reviewed between 2017 and 2024. Patients with severe IBD exacerbation were included. The primary outcome was the safety of VTE prophylaxis, investigated by increased bleeding risks during admission. This included worsening bloody stool frequency, a drop in hemoglobin (>1 g/dL from baseline) and development of hemorrhagic shock. Worsening bloody stool frequency was defined as increased bloody stool frequency >1 from baseline before starting VTE prophylaxis. A total of 1045 patient encounters were reviewed; after applying our inclusion/exclusion criteria, 353 patients were included in our study. Most patients were hospitalized with acute severe ulcerative colitis (ASUC), 213 (60.3%), and 140 (39.7%) had Crohn’s disease (CD) exacerbation. Of the total cohort, 264 (75%) patients received enoxaparin 40 mg for VTE prophylaxis, and 89 (25%) patients received 5000 units of unfractionated heparin twice a day. Eighteen (%5) patients had a history of VTE. None of the study participants had any bleeding events, including worsening bloody stool frequency, major bleeding and development of hemorrhagic shock after starting VTE prophylaxis. Our findings suggest that there is no increased risk of bleeding in patients admitted with IBD exacerbation receiving pharmacological VTE prophylaxis during the admission period. However, prospective data, including high-risk patients (e.g., patients with cancer and pregnant women), is warranted.
Alrashed F, Safar F, Mohammad S, Alrewai A, Aldeai A, Alenezi O, Shehab M
Dysbiotic microbiota trigger colitis-associated colorectal cancer and imprint a distinctive bile acid profile in a PSC-IBD model.★ Gut | 2026-03-23
Primary sclerosing cholangitis-associated UC (PSC-UC) carries excess colorectal neoplasia despite often mild-appearing endoscopy, implicating persistent microscopic inflammation and microbiota-bile acid (BA) dysfunction. To test whether PSC-UC neoplasia is driven by transferable microbiota-mediated inflammation linked to secondary BA loss. Surveillance colonoscopies (2012-2022) from PSC-UC (n=251) and UC-only (n=8839) were compared for segmental endoscopic/histological activity and dysplasia. We generated multidrug resistance protein 2 (MDR2)-/- × interleukin (IL)-10-/- double-knockout (DKO) mice and used germ-free (GF) derivation, faecal microbiota transplantation (FMT), antibiotic conditioning and cohousing with shotgun metagenomics and liquid chromatography-tandem mass spectrometry BA profiling. PSC-UC showed greater inflammatory activity and a right-shifted dysplasia burden versus UC-only. Under specific-pathogen-free conditions, DKO mice developed early right-predominant colitis and multifocal dysplasia progressing with age. DKO communities were depleted of 7α-dehydroxylation capacity with near absence of deoxycholic and lithocholic acids and no enrichment of canonical bacterial genotoxins. GF DKO mice were protected, whereas live DKO donor FMT reinstated severe colitis and dysplasia; sterile-filtered stool supernatant was inactive. IL-10-/- donor FMT or cohousing attenuated colitis and increased recipient secondary BA, whereas wild-type/MDR2-/- donor transfers were non-colitogenic. In GF DKO mice, direct deoxycholic acid repletion caused hepatotoxicity. PSC-UC neoplasia associates with transmissible microbiota-dependent inflammation and secondary BA deficiency. Controlled restoration of BA-transforming microbial functions, rather than indiscriminate secondary BA replacement, is a rational translational direction.
Awoniyi M, El Hag M, Hernandez J, Yang Q, Evans N, Nemet I, Ngo B, Coskuner D, Zhou J, Farmer M
Intestinal Ultrasound (IUS) (2 papers)
Examining attitudes to intestinal ultrasound in inflammatory bowel disease: a national survey of Australian gastroenterologists. Therapeutic advances in gastroenterology | 2026-03-19
Intestinal ultrasound (IUS) is a non-invasive, accurate, and increasingly utilized tool for the assessment and monitoring of inflammatory bowel disease (IBD). This Australian survey, endorsed by the Gastroenterology Network of Intestinal Ultrasound (GENIUS), aimed to evaluate clinician attitudes toward IUS and identify barriers to its broader national implementation. National cross-sectional observational study. An online survey was distributed to adult and pediatric gastroenterologists and trainees across Australia, with data collected between September and December 2024. One hundred twenty-two respondents participated, comprising adult (52%), pediatric (25%), and trainee (23%) gastroenterologists, with two-thirds reporting a subspecialty interest in IBD. Nearly all agreed that IUS has clinical utility in Crohn’s disease (99%) and ulcerative colitis (96%), with 96% considering IUS standard of care in IBD. Clinical confidence in IUS was high (84%), particularly among IBD specialists (95% vs 73%; p < 0.01), though lower than for colonoscopy (98%) and magnetic resonance enterography (MRE; 97%). IUS was also perceived as more resource-efficient than colonoscopy (96%) and MRE (88%). While 82% of respondents had access to IUS, mainly in an outpatient capacity, availability was lower in non-metropolitan locations. Among clinicians without access, almost all agreed that IUS access would improve IBD care; with scarcity of IUS funding and trained personnel cited as barriers. Almost half of the respondents had completed or were undertaking IUS training, with 40% of remaining respondents interested in future training. Australian gastroenterologists widely support IUS in IBD care. Expanding access to IUS requires renewed focus on service development and training initiatives, particularly in underserved areas, and cost-effectiveness studies to support these efforts. How Australian gastroenterologists view and use intestinal ultrasound in inflammatory bowel disease Patients with inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, need close monitoring to assess disease activity and guide treatment decisions. Intestinal ultrasound (IUS) is a safe, accurate, and non-invasive imaging tool that allows clinicians to assess bowel inflammation without invasive and uncomfortable procedures such as colonoscopy and MRI. In this Australian survey, supported by the Gastroenterology Network of Intestinal Ultrasound (GENIUS), we asked gastroenterologists about their views on IUS. We received 122 responses from adult and pediatric gastroenterologists and trainees across Australia. Almost all respondents believed IUS is useful for managing IBD, and that access to IUS should be part of standard IBD care. Most felt confident using IUS to guide clinical decisions, and considered it more resource efficient than both colonoscopy and MRI. Although most respondents had access to IUS, availability was more limited in non metropolitan locations. Among respondents without access, almost all agreed that access to IUS would enhance the care of IBD patients. The main barriers identified were a lack of trained staff and funding to establish and support IUS service development. Encouragingly, nearly half of respondents had completed or were currently undertaking IUS training, and many others were interested in future training. Overall, there is strong support for the use of IUS in IBD care in Australia. Expanding access will require further investment in IUS training and service development.
Chen L, Ruddick-Collins L, An YK, Baraty B, Begun J, Boyapati RK, Bryant RV, Smith RL, Srinivasan AR
Comprehensive Imaging Evaluation and Staging of Crohn’s Disease: When and Why to Use Intestinal Ultrasound, MRE, or CTE: Current Guidelines and Future Directions.Review Diagnostics (Basel, Switzerland) | 2026-03-16
Crohn’s disease (CD) is a complex inflammatory bowel disease, defined by chronic transmural inflammation and marked heterogeneity in both anatomical distribution and disease behavior, with potential involvement of any segment of the gastrointestinal tract and multiple phenotypes. Advanced cross-sectional imaging nowadays plays a central role in CD management, reliably assessing both luminal and extraluminal inflammatory manifestations, supporting initial diagnosis, phenotypic characterization, and longitudinal monitoring of disease activity, complications and treatment response. Over the last two decades, Intestinal Ultrasound (IUS), MR Enterography (MRE), and Computed Tomography Enterography (CTE) have become central components of the diagnostic pathway. MRE has emerged as the most comprehensive, radiation-free modality for evaluating intestinal extent, inflammatory activity, and complications in Crohn’s disease. Multiparametric MRE, combining T2-weighted imaging, contrast-enhanced sequences, diffusion-weighted imaging, and cine acquisitions, enables a real “Crohn’s disease staging”, namely a thorough evaluation of the transmural inflammation, of fibrotic and fistulizing lesions in the small and large bowel, as well as in the perianal region. IUS provides a dynamic, widely accessible, safe and repeatable imaging technique that is particularly well suited for tight-monitoring strategies, early assessment of therapeutic response, and routine follow-up, especially in experienced centers. Notably CTE, despite concerns related to cumulative ionizing radiation exposure, remains indispensable in acute clinical settings owing to its rapid acquisition, broad availability, and high diagnostic accuracy for detecting abscesses, perforation, and bowel obstruction. Combined, these three modalities offer a complementary and patient-tailored framework for optimal CD management. This review outlines the pathological complexity of Crohn’s disease, traces the evolution of imaging approaches, and provides a comparative overview highlighting the specific strengths and limitations of each modality.
Maccioni F, Busato L, Bottino L, Longhi A, Valenti A, Zippi M, Catalano C
Point of Care Testing (non-IUS) (1 papers)
Biosensor-Based Detection of Calprotectin and Lactoferrin as Neutrophil-Derived Markers of Inflammatory Bowel Diseases: From Molecular Pathophysiology to Point-of-Care Platforms.Review International journal of molecular sciences | 2026-03-16
Inflammatory bowel diseases (IBD) are chronic, relapsing, immune-mediated disorders that require regular and preferably noninvasive monitoring of inflammatory activity. Fecal biomarkers of neutrophilic inflammation, namely calprotectin and lactoferrin, therefore represent key analytical targets for diagnosis and longitudinal disease management. Despite their widespread clinical use, existing publications predominantly address either their clinical relevance or individual technical solutions, without establishing a comprehensive engineering-translational framework for their biosensor-based implementation. This review bridges this gap by providing an integrative analysis of the molecular and biological nature of calprotectin and lactoferrin, the mechanisms underlying their appearance in fecal matrices, and the analytical constraints that directly influence the design of hybrid point-of-care (PoC) biosensor systems. We systematically compare major biosensing platforms, emphasizing sensor architecture, signal transduction mechanisms, and sample preparation strategies as critical determinants of sensitivity, selectivity, reproducibility, and clinical relevance. The novelty of this review lies in combining the pathophysiological context of neutrophilic inflammation with physicochemical and technological aspects of biosensor development, enabling a transition from laboratory prototypes to evaluation of real translational readiness. The practical significance resides in establishing a methodological basis for rational design of next-generation hybrid-integrated biosensor systems and outlining perspectives for digital analytics and artificial intelligence in clinically interpretable IBD monitoring.
Sitkov N, Ryabko A, Ivanov S, Cheburkin Y, Kolobov A, Khasanova D, Nikolaev V, Kaplun D, Gareev K
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