IBD Literature Report
Coverage: April 13, 2026 - April 20, 2026
120
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Surgery & Complications (20 papers)
Video vignette: robotic ileocolic resection for Crohn’s disease with enterocutaneous fistula takedown. Techniques in coloproctology | 2026-04-19
Abstract not available.
Alam IS, Bornstein Y, Simon J, Grieco M, Atallah C, Safar B, Le Leannec I, da Luz Moreira A
Robotic Versus Laparoscopic Surgery for Crohn’s Disease: A Systematic Review and Meta-Analysis with Trial Sequential Analysis. Journal of laparoendoscopic & advanced surgical techniques. Part A | 2026-04-19
Laparoscopic surgery (Lap) is widely recognized as the standard minimally invasive method for colorectal surgeries. Although robotic surgery (Rob) has seen increased adoption, its application in inflammatory bowel disease remains uncertain. A systematic search was conducted across PubMed, Scopus, and the Cochrane Central Register of Controlled Trials up to February 2026. Pooled odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs) were calculated using random-effects models. Heterogeneity was assessed via the inconsistency (I2) statistic. Trial sequential analysis (TSA) was applied to assess the robustness of the cumulative evidence. Four observational studies, including 3776 patients, were analyzed; 246 underwent Rob and 3530 underwent Lap. Compared with Lap, Rob was associated with a significantly lower rate of overall postoperative complications (OR: 0.56; 95% CI: 0.31 to 0.99; P = .047). No significant differences were observed between approaches in postoperative ileus (OR: 1.16; 95% CI: 0.67 to 2.01; P = .595), anastomotic leak (OR: 0.92; 95% CI: 0.38 to 2.22; P = .852), surgical site infection (OR: 0.70; 95% CI: 0.36 to 1.36; P = .297), reoperation (OR: 1.00; 95% CI: 0.42 to 2.35; P = .997), or stoma formation (OR: 0.47; 95% CI: 0.18 to 1.25; P = .130). The length of hospital stay was similar between groups (MD: = -0.20 days; 95% CI: = -0.80 to 0.31; P = .37). Operative time was significantly longer in Rob (MD: + 51.8 minutes; 95% CI: 32.0 to 71.6; P < .001). TSA indicated that most outcomes remained underpowered, suggesting a persistent risk of random error. Rob for Crohn’s disease is a safe and feasible minimally invasive approach, with lower overall postoperative complications than Lap. However, Rob was associated with longer operative times, while most perioperative outcomes remain comparable. Further well-designed prospective studies are required to confirm these findings.
Pompeu BF, Micherino BV, Brunini JH, Barone GL, Delgado LM, Aguiar LR, Melillo GD, Tafner PFDA, Theis C, Del Grande LM
Hyperechoic mesenteric fat on preoperative intestinal ultrasound predicts early postoperative recurrence in Crohn’s disease. Insights into imaging | 2026-04-16
To investigate the value of hyperechoic mesenteric fat (HMF) detected by preoperative intestinal ultrasound (IUS) in predicting early postoperative recurrence (EPR) in patients with Crohn’s disease (CD). This retrospective study included 124 CD patients who underwent I-stage intestinal resection. Based on 1-year postoperative recurrence, patients were stratified into EPR (n = 59) and non-EPR (n = 65) groups. Clinical parameters (such as smoking history, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), immunosuppressive therapy) and IUS parameters (such as bowel wall thickness (BWT), HMF, abscess/fistula) were compared. Univariate and multivariate logistic regression identified EPR predictors. EPR occurred in 59 patients (47.6%) during the 1-year follow-up. Significant differences (p < 0.05) were observed between EPR and non-EPR groups for clinical factors (smoking history, elevated preoperative CRP/ESR, postoperative immunosuppression) and IUS parameters (HMF, BWT, and abscess/fistula). HMF demonstrated superior discriminative capacity for EPR prediction (area under the curve (AUC) = 0.808, 95% confidence interval (CI): 0.728-0.873) vs BWT (AUC = 0.618, p < 0.05) and abscess/fistula (AUC = 0.599, p < 0.05). Univariate analysis identified CRP, ESR, colonic disease, immunosuppression, HMF, abscess/fistula, and BWT as candidate predictors (p < 0.05), with multivariate analysis confirming HMF as an independent predictor (adjusted odds ratio (OR) = 18.810, 95% CI: 6.459-54.775; p < 0.001). Preoperative IUS-detected HMF may serve as a valuable predictor for assessing EPR risk in patients with CD. Preoperative IUS identification of HMF provides a practical, non-invasive biomarker that enables radiologists to critically improve risk stratification for EPR in CD. EPR poses a significant clinical challenge in the management of CD. HMF detected on preoperative IUS is a strong, independent predictor for EPR, with superior predictive performance compared to other established IUS parameters. Assessing HMF provides a valuable, non-invasive imaging biomarker for preoperative risk stratification.
Liang Z, Chen S, Cheng W, Qin S, Hong X, Guan X, Zhou J, Liu G
Treatment and Outcomes of Crohn’s Disease and Ulcerative Colitis in Newly Diagnosed Adults in the United States, 2007-23.★ Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association | 2026-04-15
We examined treatment and outcomes of inflammatory bowel diseases (IBD) in a contemporary and diverse cohort of adults with newly diagnosed IBD in a large, commercially insured U.S. Using an administrative claims database (OptumLabs® Data Warehouse), we created an inception cohort of physician-diagnosed IBD between 2007-23. We examined cumulative incidence of hospitalization, surgery, safety events and medication use in patients with Crohn’s disease (CD) and ulcerative colitis (UC). Among 3,044 adults with newly diagnosed CD (age at diagnosis, 39±15y; 47% male; 83% White, 7.5% Black and 7.1% Hispanic patients) followed over mean 4.3±3.1y, 5-year risk of IBD-related hospitalization, major surgery and serious infections was 16%, 12%, and 13%, respectively, with no consistent racial and ethnic, age or sex differences. In patients diagnosed between 2019-23, 1-y cumulative use of corticosteroids and advanced therapy was 44% (22% with ≥2 courses) and 53%, respectively, without significant racial and ethnic, age or sex differences. Among 3,893 patients with newly diagnosed UC (age at diagnosis, 41±14y; 52% male; 80% White, 7.2% Black and 8.2% Hispanic patients) followed over 4.2±3.0y, 5-year risk of IBD-related hospitalization, colectomy and serious infection was 11%, 6%, and 10%, respectively, with lower risk in Hispanic patients (vs. White patients). In patients diagnosed between 2019-23, 1y cumulative use of corticosteroids and advanced therapy was 47% (26% with ≥2 courses) and 27%, respectively, with earlier initiation of advanced therapies in more recent time periods, and with lower utilization of advanced therapies in Hispanic patients. In a contemporary and diverse cohort of commercially insured adults with newly diagnosed IBD in the U.S., excess corticosteroid use is decreasing in recent era, along with early initiation of advanced therapies. No consistent racial and ethnic, age or sex differences were identified.
Ahuja D, Park SK, Qi Y, Patel SB, Jairath V, Xu R, Boland BS, Lewis JD, Kappelman MD, Goodwin SW
Adverse Childhood Experiences and Disease Activity Are Associated with Post-Traumatic Stress Symptoms in Crohn’s Disease. Advances in therapy | 2026-04-15
Crohn’s disease (CD) is a chronic inflammatory bowel disease associated with a substantial psychological burden, including post-traumatic stress symptoms (PTSS). However, PTSS do not develop in all patients, suggesting individual vulnerability factors. Adverse childhood experiences (ACEs) are a transdiagnostic risk factor for stress-related psychopathology and may influence psychological responses to chronic disease. We examined whether ACEs moderate the relationship between clinical disease activity and PTSS in patients with CD. In this cross-sectional study, outpatients with CD completed self-report measures assessing PTSS and ACEs. Clinical disease activity was assessed using the Harvey-Bradshaw Index. Data were analyzed using Pearson correlation coefficients and hierarchical moderated regression analyses. A total of 161 outpatients with CD were included. Clinically significant PTSS were observed in 32.1% of the sample. Disease activity was positively associated with PTSS (r = .33, p < .01), as was cumulative ACE exposure (r = .38, p < .01). In regression analyses, both disease activity (β = .22, p = .013) and ACEs (β = .35, p < .001) independently predicted PTSS, whereas disease duration was inversely associated (β = - .19, p = .047). A significant interaction between disease activity and ACEs emerged (ΔR2 = .034, p = .013), indicating a stronger association between disease activity and PTSS among patients with greater childhood adversity. Early-life adversity appears to increase vulnerability to PTSS in the context of active CD. ACE-informed assessments may help identify patients at higher psychological risk and guide trauma-informed clinical care.
Spagnolo G, Ferrarese D, Di Vincenzo F, Iaccarino J, Murgiano M, Vecchione M, Sicilia G, Napolitano D, D’Onofrio AM, Gasbarrini A
Editorial: Beyond Resection-Rethinking Postoperative Management in Colonic Crohn’s Disease.Editorial★ Alimentary pharmacology & therapeutics | 2026-04-15
Exclusive enteral nutrition and the risk of nonsurgical readmission in patients with Crohn’s disease-related intra-abdominal abscess: A retrospective cohort study. JPEN. Journal of parenteral and enteral nutrition | 2026-04-15
Intra-abdominal abscess management in Crohn’s disease patients represents a significant clinical challenge. This study sought to assess the impact of exclusive enteral nutrition on nonsurgical readmission in patients with Crohn’s disease-related intra-abdominal abscess. This retrospective cohort study was conducted between January 2016 and June 2022 included Crohn’s disease patients hospitalized for intra-abdominal abscess. Patients were categorized based on exclusive enteral nutrition administration during hospital stay or not. The primary outcome was nonsurgical readmission within 1-year post-discharge. Secondary outcomes included surgical intervention and abscess recurrence. Multivariable logistic regression analysis and Cox regression analysis were performed to adjust for potential confounding factors. A total of 128 patients were enrolled, with 45 allocated to the exclusive enteral nutrition group and 83 to the nonexclusive enteral nutrition group. Compared to the nonexclusive enteral nutrition group, patients treated with exclusive enteral nutrition were less likely to require nonsurgical readmissions (42.2% vs 79.5%, P < 0.001). The multivariate analysis confirmed exclusive enteral nutrition as an independent protective factor against nonsurgical readmissions (hazard ratio: 0.11; 95% confidence interval: 0.04-0.30; P < 0.001). In addition, exclusive enteral nutrition group showed a significantly lower rate of surgical intervention (46.7% vs 75.9%, P = 0.01). Notably, abscess recurrence rates remained comparable between groups. This study provides novel evidence that exclusive enteral nutrition is associated with reduced risks of nonsurgical readmission and surgical burden without affecting abscess recurrence rates in patients with Crohn’s disease-related intra-abdominal abscess.
Zhang Z, Cai T, Xie H, Luo R, Liu H, Li W, Zeng Z, Liang Z, Xiong L, He X
Histopathologic evaluation and reporting in inflammatory bowel disease A consensus paper sponsored by the Rodger C. Haggitt Gastrointestinal Pathology Society.Review Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc | 2026-04-13
The histopathologic evaluation and diagnosis of specimens from patients with inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn disease (CD), is complicated, yet clinically important. Therefore, formalized recommendations about appropriate terminology and necessary elements to include in the corresponding report are likely to benefit practicing pathologists. This consensus paper was initiated and sponsored by the Rodger C. Haggitt Gastrointestinal Pathology Society (GIPS) after the majority of respondents in a survey indicated that IBD reporting guidelines would inform their daily practice. The document presented herein provides recommendations for the macroscopic and histologic examination of samples from patients with suspected or confirmed IBD at three distinct tiers of disease evolution: initial diagnosis with endoscopic biopsies, disease activity assessment during colonoscopic surveillance, and evaluation of long-term prognosis after surgery. Given its complexity and importance, IBD-related neoplasia will be considered in a separate, forthcoming document. These recommendations, presented in the form of 20 main position statements, each following a brief review of the pertinent literature and some with additional supplemental statements, reflect the strength of available published evidence. They were subjected to review, vote, and approval by all authors and, in addition, by a group of surgical pathologists and gastroenterologist clinicians with documented interest and experience in the diagnosis and treatment of patients with IBD. We hope this document is the first in a dynamic series with subsequent iterations and revisions incorporating emerging data and evolving approaches to management.
Polydorides AD, Liu X, Hu S, Drage MG, Colombel JF, McGovern DPB, De Hertogh G, Deshpande V, Vieth M, Panarelli NC
A web-based prediction model using routinely available clinical variables to estimate surgical risk in Crohn’s disease during remission or mild activity. Scientific reports | 2026-04-13
Abstract not available.
Xie K, Yao H, Jiang Z, Liu H, Sun Q, Yang L, Yuan L
Malignancy in Long-Standing Perianal Fistulizing Crohn’s Disease: Too Little, Too Late. Digestive diseases and sciences | 2026-04-13
Perianal fistulizing Crohn’s disease (PFCD) is a chronic, aggressive phenotype associated with an elevated risk of malignancy arising within long-standing fistula tracts. Although rare, PFCD-associated cancers carry a poor prognosis and are often diagnosed late due to overlapping symptoms with active inflammatory disease and the absence of established screening guidelines. We present a case of a 71-year-old man with nearly 50 years of untreated PFCD, who developed mucinous adenocarcinoma arising from a chronic perianal fistula. Despite multiple hospitalizations for recurrent abscesses, sepsis, and fistulizing disease, he initially declined definitive surgical and medical therapy, and later was unable to be initiated on advanced Crohn’s treatments due to ongoing infections. Progressive enlargement of a complex perianal abscess and new pelvic collections raised concern for malignant transformation, and exam under anesthesia (EUA) with drainage ultimately revealed mucinous adenocarcinoma. His clinical course rapidly deteriorated, preventing oncologic therapy initiation, after which he was transitioned to hospice. This case highlights key diagnostic challenges in PFCD-associated cancer, including the difficulty distinguishing malignancy from active inflammation with imaging and the need for biopsy via EUA for confirmation. Persistent or new perianal symptoms in patients with long-standing PFCD-particularly beyond 10 years-should prompt urgent evaluation. Although formal guidelines are lacking, early involvement of a multidisciplinary team is essential to optimize diagnosis and management. Greater awareness of this rare complication is needed to support earlier recognition and to inform future strategies for screening and treatment.
Goyal A, Syal G, Fleshner P, Gu P
Early immunomodulator therapy reduces the risk of intestinal resection in Crohns disease: a systematic review and meta-analysis.★ Inflammatory bowel diseases | 2026-04-13
The optimal timing for initiating immunomodulators (IMs) in Crohns disease (CD) remains unclear. We assessed whether early IM therapy reduces the risk of intestinal resection. MEDLINE, EMBASE, and the Cochrane Library were systematically searched for studies comparing outcomes by timing of IM (thiopurines or methotrexate) initiation in CD. The primary outcome was intestinal resection. Pooled hazard ratios (HRs) with 95% CIs were calculated using a random-effects model. Seven cohort studies including 4297 patients were analyzed. Early IM initiation was associated with a 47% lower risk of intestinal resection compared with late or no IM therapy (pooled HR, 0.53; 95% CI, 0.44-0.65; I2 = 23%). This protective effect was consistent across subgroups, including studies in which all patients received IMs and early initiation was associated with a lower risk than late initiation (HR 0.59; 95% CI, 0.42-0.83). When early treatment was defined as initiation within 1-2 years of diagnosis, early IM use was associated with a lower risk of intestinal resection than late or no IM therapy, with no heterogeneity (HR 0.55; 95% CI, 0.43-0.70; I2 = 0%). A broader definition of early treatment as within 3 years of diagnosis also showed benefit compared with late or no IM therapy (HR, 0.52; 95% CI, 0.37-0.74) but with moderate heterogeneity (I2 = 57%). Early IM therapy is associated with a substantially lower risk of intestinal resection in CD compared with later or no IM therapy. The most consistent benefit occurs when treatment is initiated within the first 1-2 years after diagnosis, supporting the concept of a therapeutic “window of opportunity” during which timely IM initiation may favorably alter the disease course. Early use of immunomodulators in Crohns disease—especially within 1-2 years after diagnosis—significantly reduces the risk of intestinal surgery. This meta-analysis of 7 cohort studies supports a therapeutic “window of opportunity” for timely treatment to improve long-term outcomes.
Yoon J, Jun YK, Lee HS, Yoo JH, Park JJ
Frailty in inflammatory bowel disease: a missing link in personalized care for the aging IBD population.★ Inflammatory bowel diseases | 2026-04-11
Frailty is a potentially reversible condition that reflects decreased physiological reserve and is increasingly recognized in older patients with inflammatory bowel disease (IBD). Although frailty is frequently associated with advanced age, multi-morbidity, and disease severity, this condition represents a distinct clinical syndrome with independent prognostic significance that warrants dedicated assessment. We performed a narrative review of studies exploring frailty in patients with IBD, focusing on definitions, prevalence, assessment tools, clinical implications, and interventions. Two main conceptual models of frailty have been applied to IBD: the phenotypic model, an individual-level assessment defining frailty as a syndrome; and the cumulative deficit model, which is suited for retrospective identification. While eleven frailty tools have been used in IBD studies, none were specifically designed or validated for the IBD patient population. Owing to heterogeneous definitions and populations, the reported prevalence of frailty in IBD patients ranges from 6% to 62%. Frailty is associated with increased risks of hospitalization, prolonged hospitalization, postoperative complications, infections, and mortality. Key drivers of frailty in IBD include fatigue, sarcopenia, and malnutrition, common features of IBD that may share mechanisms. While these factors contribute to frailty, the syndrome itself independently predicts adverse clinical outcomes. Current limitations include heterogeneous definition, underrepresentation of older patients, lack of longitudinal data, and absence of IBD-specific tools. Frailty is a critical, under-recognized determinant of poor outcomes in IBD. Systematic screening and integration into care pathways could improve patient stratification and management. Future research should aim to validate specific assessment tools and test interventions to ameliorate frailty in older IBD patients. Frailty is a common but often overlooked condition in older patients with inflammatory bowel diseases (IBD). In this review we show that frailty in IBD patients strongly predicts complications and death, independently of disease activity, and highlights the need for screening and tailored interventions in IBD care.
Le Cosquer G, Gilletta C, Kochar B, Ananthakrishnan AN, Buisson A
Effect of polydeoxyribonucleotide as a potential therapeutic agent to enhance the healing of Crohn’s perianal fistula.★ Inflammatory bowel diseases | 2026-04-11
The treatment of Crohn’s perianal fistula remains challenging owing to its recurrent nature and resistance to complete healing. This study aimed to assess the postoperative outcomes, including fistula closure rates, following Crohn’s perianal fistula surgery, with and without polydeoxyribonucleotide administration. A retrospective review was conducted on patients who underwent fistula closure operations for Crohn’s perianal fistula at a single tertiary center in Seoul, Korea, between January 2018 and June 2024. Patients were divided into two groups based on the use of local polydeoxyribonucleotide (PDRN) injections during fistula closure operations, and clinical variables and postoperative outcomes were compared between the groups. Among the 47 patients, 21 (44.7%) were assigned to the PDRN group and 26 (55.3%) were assigned to non-PDRN group. Baseline characteristics between the two groups showed no significant difference. During the mean follow-up of 30.4 months, patients in the PDRN group demonstrated a significantly higher complete fistula closure rate (70.0% vs 26.9% at 6 months, and 83.3% vs 46.2% at 12 months; P = .005), and a shorter time from surgery to complete closure (3.3 ± 2.6 months vs 5.9 ± 3.8 months; P = .044), compared with the non-PDRN group. Multivariate analysis revealed PDRN as an independent factor significantly associated with Crohn’s perianal fistula closure (HR 2.336; 95% CI, 1.092-4.997, P = .029). PDRN is a potential therapeutic agent that presents a viable option for Crohn’s perianal fistula surgery, improving complete fistula closure rate through a safe, cost-effective, and relatively simple procedure. This study suggests the feasibility of using polydeoxyribonucloetide as a potential therapeutic agent that may facilitate more frequent and accelerated fistula closure following Crohn’s perianal fistula surgery, highlighting its safety, practicality, and cost-effectiveness.
Kim HK, Yoon YS, Lee JL, Park EJ, Kim MH, Kim YI, Kim CW, Park IJ, Lim SB, Yu CS
Lack of disparities in postoperative care after ileocecal resection in patients with Crohn’s disease at tertiary inflammatory bowel diseases centers. Therapeutic advances in gastroenterology | 2026-04-08
Prior studies suggest that longer drive time (DT) to specialists and higher area deprivation index (ADI) are linked to worse outcomes in inflammatory bowel disease (IBD), but their impact on postileocolic resection (ICR) care in patients with Crohn’s disease (CD) is not well defined. We aimed to evaluate disparities in post-ICR care based on DT and ADI. Spatial analysis was performed with ArcGIS Pro to geocode patient and medical facility addresses with StreetMap Premium locators. High DT was defined as >60 min from the center. Data were analyzed using basic statistics and multivariate logistic regression. A retrospective cohort study was performed of CD patients’ post-ICR care at two tertiary-care IBD centers (January 2018-March 2023). Our study included 293 patients; 44% had high DT. High DT had a higher median number of preoperative advanced therapy (2 vs 1, p = 0.007). Despite this, there was no difference between cohorts in median days to postop ileocolonoscopy (IOE; 257 vs 332, p = 0.59) and surgical recurrence rate (21% vs 27%, p = 0.278). Tobacco use and perianal disease were associated with increased odds of postoperative IOE (adjusted odds ratio (aOR) 2.09) and advanced therapy initiation (aOR 2.00). We identified no differences in postoperative colonoscopy timing or surgical recurrence in patients with CD at two tertiary IBD centers based on DT or ADI. Given the lack of disparities in care delivery among patients treated in tertiary IBD centers, further comparative studies to care outside of specialized networks are needed to evaluate whether centralization to IBD centers is superior. Lack of disparities in postoperative care after ileocecal resection in patients with Crohn’s disease at tertiary inflammatory bowel diseases centers This study assessed post-ICR care disparities in Crohn’s disease based on drive time and area deprivation. Among 293 patients, no differences in post-op care or recurrence were found, suggesting equitable care at tertiary IBD centers, regardless of geographic or socioeconomic factors.
Coombs S, Powell M, Johnson K, Hu J, Webb M, McDaniel P, Deepak P, Barnes EL
Genetic correlation between inflammatory bowel disease and educational attainment: unveiling shared genetic mechanisms. Psychiatric genetics | 2026-04-06
A potential genetic link between inflammatory bowel disease (IBD) and educational attainment has been suggested. Understanding the underlying mechanisms of this genetic relationship is crucial for advancing the knowledge of their co-occurrence patterns. Using genome-wide association study data for both IBD and educational attainment, a multiphase analytical approach was applied to examine their genetic correlation. The study involved three phases: first, linkage disequilibrium score regression and high-definition likelihood models were used to assess genome-wide genetic correlation; second, SUPERGNOVA was employed to analyze the genetic structure across specific chromosomal regions; and third, conditional/conjunctional false discovery rate (cond/conjFDR) methods were applied to measure genetic overlap and identify shared genetic loci between the two traits. The genome-wide analysis revealed significant genetic correlations between IBD, especially Crohn’s disease, and educational attainment, while the association with ulcerative colitis was weaker. Regional analyses identified localized genetic correlation signals across several chromosomal regions between these traits. The application of the conjFDR framework confirmed the presence of overlapping genetic components, leading to the identification of key genetic variants contributing to disease susceptibility and progression. This genetic study provides new theoretical insights into the association between IBD and educational attainment, contributing to a deeper understanding of the mechanisms underlying their co-occurrence.
Hong Z, Yin H
Prognostic Utility of Albumin and the C-Reactive Protein-to-Albumin Ratio for Predicting Intravenous Steroid Response in Acute Severe Ulcerative Colitis. Journal of clinical medicine | 2026-04-04
Background/Objectives: Acute severe ulcerative colitis (ASUC) is a high-risk condition associated with intense inflammation and a substantial risk of early colectomy. Intravenous steroids (IVS) remain the first-line therapy; however, steroid nonresponse is common. While the C-reactive protein-to-albumin ratio (CAR) has been proposed as a prognostic marker, data on its dynamic changes and late-phase performance remain limited. This study aimed to evaluate the serial performance of albumin and CAR at days 3 and 7 and to assess their association with early and delayed steroid response in a real-world cohort of biologic-naive ASUC patients. Methods: Biologic-naive patients hospitalized with ASUC between 2010 and 2023 were retrospectively analyzed. Disease severity and treatment response were defined using Truelove-Witts and Oxford criteria. Clinical and biochemical parameters, including albumin, CAR, and neutrophil-to-lymphocyte ratio (NLR), were assessed at baseline and on days 3 and 7. Associations with steroid response were evaluated using ROC analysis and multivariable logistic regression. Results: Ninety-eight patients were included. The IVS response rate was 11.2% on day 3 and 56.1% by day 7. Among nonresponders, 25% required infliximab rescue therapy, and colectomy occurred in 12.2%. Although day 3 CAR showed a trend toward discrimination, this did not reach statistical significance (p = 0.098) and should be considered exploratory. By day 7, responders had significantly higher albumin levels and lower CAR values (p < 0.05). Albumin (AUC = 0.702) and CAR (AUC = 0.713) demonstrated comparable performance. In multivariable analyses, day 7 albumin and CAR were significantly associated with steroid response, whereas NLR was not associated. Conclusions: Albumin and CAR are clinically relevant biomarkers associated with steroid response in ASUC. Early changes, particularly in CAR, may provide preliminary signals of nonresponse but require cautious interpretation. In contrast, day 7 measurements appear to reflect ongoing inflammatory dynamics and treatment evolution rather than true baseline predictors. Serial assessment of these biomarkers may support treatment monitoring and help optimize the timing of rescue therapy.
Süleyman S, Emin P, Hüseyin A, Çağatay A, Şehmus Ö, Kamil Ö
Evaluation of Long-Term Outcomes of Crohn’s Disease Complicated by Intra-Abdominal Abscess: A Retrospective International Cohort Study. Journal of clinical medicine | 2026-04-03
Background: Crohn’s disease complicated by intra-abdominal abscesses often requires surgery. Percutaneous drainage may prevent surgery, but optimal post-drainage management is unclear. We aimed to analyze the long-term outcomes of Crohn’s disease with intra-abdominal abscesses after intervention. Methods: Patients with penetrating Crohn’s disease and a single intra-abdominal abscess were enrolled in this multicenter, international, retrospective study after the detection of the abscess (baseline), with a minimum follow-up of 12 months. Those requiring urgent bowel resection were excluded. Patients were grouped by elective surgical need after successful (catheter insertion with effective drainage) percutaneous drainage (controls: no pre-resection drainage). The primary outcome was abscess recurrence. We also assessed stoma rate, post-procedural complications, hospitalizations, advanced treatment need, postoperative luminal recurrence, and need for re-drainage. Results: We studied 157 patients with Crohn’s disease (9 countries; males: 58%, median age: 32.4 [interquartile range: 25-39 years]); 89/157 underwent percutaneous drainage (median follow-up: 95.9 weeks [interquartile range: 58-104]). Abscess recurrence did not differ by drainage (p = 0.221). Abscess size was associated with advanced-treatment initiation (Odds ratio: 0.978; 95% confidence interval: 0.960-0.997, p = 0.023) and postoperative luminal recurrence (Odds ratio: 1.044, 95% confidence interval: 1.012-1.078, p = 0.007). Time to resection was longer after drainage, and ROC analysis raised predictive value for re-drainage (16.6 weeks post-drainage; AUC = 0.82, 95% confidence interval: 0.73-0.92). Patients without drainage had more post-procedural complications. Conclusions: Abscess size should guide management. Delayed resection may increase re-drainage odds, whereas surgery alone may have higher complication rates. Percutaneous drainage can safely postpone resection.
Bacsur P, Nemeczek S, Filip R, Fousekis F, Mpakogiannis K, Kagramanova A, Argyriou K, Pastras P, Triantos C, Miheller P
Complete pathological response to neoadjuvant chemoradiotherapy in Crohn’s disease-associated fistula adenocarcinoma: a case report.Case report Frontiers in medicine | 2026-04-01
Fistula-associated adenocarcinoma (FAA) in Crohn’s disease is an exceptionally rare and aggressive complication, often diagnosed late and historically managed with immediate radical surgery. Critically, the role of neoadjuvant chemoradiotherapy has remained undefined, with no reported cases of complete pathological response to date. We report the case of a 52-year-old man with longstanding Crohn’s disease who developed a mucinous adenocarcinoma arising from a chronic perianal fistula, initially revealed by a perineal abscess. Histopathological analysis confirmed the diagnosis. Staging work-up demonstrated no evidence of distant metastasis. The patient underwent neoadjuvant chemoradiotherapy according to the PRODIGE-23 protocol, followed by abdominoperineal resection. Pathological assessment of the resection specimen demonstrated a complete pathological response (ypT0N0). This case highlights the importance of maintaining high clinical suspicion for malignant transformation in patients with chronic perianal fistulas in Crohn’s disease and provides the first evidence that complete pathological response is achievable in fistula-associated adenocarcinoma, suggesting that neoadjuvant multimodal therapy may allow exploration of organ-preserving approaches in this rare condition.
Dahmeni W, Souilem E, Hassen H, Ghdiri Y, Ahlem Z, Dahmoul A, Slama AB, Brahem A, Jaziri H, Mestiri S
Impact of Delayed Diagnosis in IBD on Clinical Outcomes and Healthcare Delivery. Diagnostics (Basel, Switzerland) | 2026-03-30
Background: Delays in diagnosis are unfortunately quite common in most health systems. It is apparent that timely diagnosis is more likely to have a favourable outcome. However, there may be many reasons why timely diagnosis is not always achieved. The aim of our study was to report on the impact of delays on IBD-related adverse outcomes (AOs). Methods: New patients referred for suspected IBD to a single tertiary care centre between January 2013 to December 2017 were identified using EMR. For purposes of the study, a cut-off time was set by investigators for each delay-type based on best average hospital waiting times. The reasons for delays in patient journey until start of treatment and data on pre-defined AOs (steroid & other rescue therapies, hospitalisations, surgery) were recorded for each patient until end of June 2021. The data were analysed using multiple Pearson correlations and Cox proportional Hazard model to determine whether there is a difference in survival without AOs between patients with and without a delay. Results: Total of 105 patients were identified using stringent criteria (M = 58; median age = 32 y) with a long median follow-up of 55 months. 65, 27 and 13 patients had final diagnosis of Ulcerative colitis, Crohn’s disease and Unclassified colitis respectively, and analysed collectively. In our cohort, the longest delay-types noted were-patients seeking medical attention (median = 4 months; range 1 to 84 months), arranging gastroenterology clinic review after referral from primary care (median = 5 weeks; range 1 to 30 weeks), and waiting for index endoscopy (median = 3 weeks; 1 to 36 weeks). Patient stratification based on delay-type using specific cut-off times for each showed a statistically significant difference in survival without AOs for all (when comparing delay v/s no delay). Conclusions: In our cohort we report that delays, and subsequent untreated chronic inflammation, leads to poor outcomes in patients with newly diagnosed IBD regardless of whether delays are patient-related or health-system-related. Also, cumulative delays in the hospital appear to increase the use of biologics in consecutive years. Understanding these factors help rectify and offer long-term solutions.
Shivaji UN, Majumder S, Rao A, Bazarova A, Parigi TL, Ghosh S, Iacucci M
Dietary Management After Ulcerative Colitis Surgery: A Thematic Analysis of TikTok Content. Nutrients | 2026-03-30
Background/Objectives: For patients with Ulcerative Colitis (UC) requiring surgical treatment, post-operative dietary management can pose significant challenges. TikTok is emerging as a popular social media platform for dissemination of health and nutrition information. The aim of this study is to analyse patient-generated content on TikTok regarding dietary management post-UC surgery, in order to identify recurring themes and highlight patient priorities. Methods: Relevant TikTok videos were identified through a systematic search. Search terms were developed by combining ‘diet UC’ or ‘nutrition UC’ with common UC surgical procedures. From each search term, the first 10 videos were screened. If a search produced fewer than 10 results, all identified videos were retrieved. Inclusion criteria were videos in English, and a strong indication that the content creator was diagnosed with UC and had undergone relevant surgery, and was providing nutrition recommendations. Thematic analysis of video transcripts was conducted using Braun and Clarke’s framework to identify common themes. Results: A total of 89 videos, created between 2021 and 2024, were found on the initial search, of which 12 duplicates were removed, and 77 videos were screened. Sixteen English language videos met the inclusion criteria and were analysed. Thematic analysis identified three overarching themes: (1) adaptive dietary progression in the post-surgical period, where patients described a phased approach to reintroducing foods post-surgery; (2) personalisation of diet, highlighting individualised strategies for symptom and hydration management; and (3) Emotional and social impact of dietary restrictions and modifications, including fear of food and social isolation. Conclusions: This thematic analysis offers an insight into how patients navigate the complex management of diet following UC surgery. It is important for clinicians to discuss the dietary information and online content patients are exposed to in relation to their condition. Additionally, clinical practice should evolve to embrace patient-centred, multidisciplinary approaches that validate lived experience, ensure consistent dietary guidance, and address the psychological burden of dietary restriction.
Kaye OR, Rhys-Jones DR, Argyriou O, Blackwell S, Halmos EP, Ardalan Z, Warusavitarne J, Sahnan K, Segal JP, Hart AL
Therapeutics & Mechanisms (13 papers)
Integration of Ustekinumab Biosimilars into Inflammatory Bowel Disease Care: Evidence, Implementation, and Patient-Centered Considerations.Review Advances in therapy | 2026-04-18
The recent introduction of ustekinumab biosimilars represents a pivotal advancement in the management of inflammatory bowel disease (IBD), offering opportunities to enhance access to advanced therapy and reduce healthcare costs without compromising treatment efficacy. IBD, encompassing Crohn’s disease and ulcerative colitis, imposes a substantial economic burden on patients and the health care system, with biologics driving most direct costs. Biosimilars have successfully reduced expenditures across various therapeutic classes, notably anti-tumor necrosis factor agents, and now extend these benefits to interleukin-12/23 inhibitors. This review summarizes the regulatory, clinical, and practical considerations for integrating ustekinumab biosimilars into IBD care in the United States. Food and Drug Administration approval is based on rigorous totality-of-evidence evaluations, leveraging pharmacokinetic, immunogenicity, and efficacy studies in sensitive populations such as moderate-to-severe plaque psoriasis, with regulatory extrapolation to IBD indications. Clinical trials of eight ustekinumab biosimilars have consistently demonstrated therapeutic equivalence, including maintenance of efficacy and safety following single or multiple switches from the reference product. Implementation in IBD practice requires careful navigation of operational and patient-centered challenges. Key considerations include coordination of intravenous induction and subcutaneous maintenance therapy across medical and pharmacy benefits, product-specific storage and device differences, and proactive mitigation of the nocebo effect through shared decision making and structured patient education. Ustekinumab biosimilars are poised to expand therapeutic accessibility and support healthcare cost containment. Successful adoption will depend on clinician familiarity, streamlined operational workflows, and patient-centered strategies to maintain confidence, minimize treatment disruption, and optimize long-term outcomes in IBD management.
Piche SL, Becker MD, Bhat S, Huang LL, Kane SV
Intestinal epithelial cell-specific deletion of Jak2 disrupts gut homeostasis. Scientific reports | 2026-04-17
Disruption of the intestinal epithelial barrier is recognized as a driver of inflammatory bowel disease (IBD) pathogenesis, yet the signaling pathways that govern epithelial integrity remain incompletely defined. Among these, Janus kinase (JAK)-mediated signaling plays a role in intestinal epithelial cells (IECs), coordinating barrier function and host defense. However, the role of JAK2 in IECs remains poorly understood. To investigate the in vivo role of epithelial JAK2, we generated mice with IEC-specific Jak2 deletion using the Villin-Cre system. These mice were born at expected Mendelian ratios and normal body weights. By 12 weeks of age, they developed shortened colons and exhibited mild small intestinal inflammation under homeostatic conditions. Histological analysis revealed increased neutrophilic infiltration and epithelial damage in the small intestine, without overt colitis. JAK2 deficiency led to increased intestinal permeability, with altered expression of genes that determine tight junctions, and a skewed cytokine gene expression profile marked by elevated Il13 and Il17 and reduced Il1-β and Il6. When subjected to dextran sodium sulfate (DSS)-induced colitis, Jak2-deficient mice exhibited sex-dependent weight loss. These findings show that IEC-specific JAK2 promotes barrier integrity and constrains low-grade inflammation under homeostatic conditions, highlighting a previously underappreciated role for epithelial JAK2 in mucosal regulation.
D’Mello B, Rivera D, Rehal S, Pollock-Tahiri E, Li YZ, Dodington D, Wagner KU, Streutker C, Woo M
Response to: The Long Game in Ulcerative Colitis: Mirikizumab’s Four-Year Outcomes.Editorial★ Inflammatory bowel diseases | 2026-04-16
Corticosteroid Initiation Before Antimicrobials Does Not Increase the Risk of Adverse Outcomes Among Individuals Hospitalized With an IBD Flare and Enteric Infection. Journal of clinical gastroenterology | 2026-04-16
To investigate the safety of corticosteroid escalation before antimicrobial treatment among inflammatory bowel disease (IBD) flares associated with an enteric infection. Corticosteroids are often necessary to treat individuals with IBD; however, there is concern that immunosuppression in the setting of a gastrointestinal infection may worsen outcomes. We conducted a retrospective study of adults (18 y or older) hospitalized for an IBD flare (2015 to 2023) who received both systemic corticosteroids and antimicrobials for a gastrointestinal infection. The primary outcome was a composite of in-hospital death, IBD-related surgery, need for intensive care unit, toxic megacolon, or acute kidney injury, stratified by timing of corticosteroid escalation (before vs. after antimicrobial initiation). Outcomes at 90 days were also collected in a secondary analysis. Overall, 76 individuals were included; 48 (63.2%) had ulcerative colitis. The most common infection was Clostridioides difficile (n=50; 65.8%), and the majority of patients (n=51, 67.1%) received corticosteroid initiation (or escalation) before antimicrobials. There was no significant difference in the development of the primary (9.8% vs. 8.0%, P=1.00) or secondary (29.4% vs. 32.0%, P=0.82) outcome based on corticosteroid initiation before versus after antimicrobial initiation. Among patients with C. difficile, similar results were seen. Among patients hospitalized with an IBD flare complicated by enteric infection, initiation or escalation of corticosteroids before antimicrobial therapy did not increase the risk of in-hospital or 90-day adverse events. This study supports the notion that corticosteroids can be safely utilized while awaiting the results of the gastrointestinal infectious testing.
Montgomery S, Axelrad JE, Delau O, Shaukat A, Faye AS
Is standard induction with mirikizumab sufficient in refractory ulcerative colitis in real-world practice?Letter European journal of hospital pharmacy : science and practice | 2026-04-15
Abstract not available.
Calvo Arbeloa M, Elcano Aguirre I, Arrondo Velasco A, Sarobe Carricas M
Ustekinumab resistance in individuals with ulcerative colitis is associated with an alteration of a subset of proinflammatory mucosal regulatory T cells.★ Inflammatory bowel diseases | 2026-04-15
Ustekinumab is a monoclonal antibody therapy targeting interleukin-12 and interleukin-23 for the treatment of inflammatory bowel diseases, including ulcerative colitis (UC). While these pathways remain quite attractive for UC therapy, response to ustekinumab can be variable. There is an urgent need to better understand the underlying mucosal immune alterations associated with treatment to guide therapy decisions. This study aims to examine the mucosal immune signatures in individuals with UC with variable treatment response to ustekinumab. Sigmoid colon tissue from individuals treated with ustekinumab were analyzed using a multimodal approach. Single-cell RNA and T cell receptor sequencing was performed on mucosal biopsies. In a subset of these patients, multiparameter flow cytometry and spatial transcriptomics was also completed on matched pre- and post-treatment tissue samples. Key findings were also validated on a larger cohort using immunohistochemistry. Ustekinumab significantly altered the frequency and phenotype of mucosal regulatory T cells (Tregs). Nonresponders to ustekinumab had a higher frequency of Tregs that expressed OX40 and GITR, which is associated with decreased suppressive abilities. In contrast, responders had Tregs with elevated GPR15 and reduced expression of the kinase PIM2, which can alter Treg stability and function. Additionally, T helper 17 cells in nonresponders demonstrated an enhanced proinflammatory gene expression profile. Nonresponse to ustekinumab in UC is linked to a mucosal immune environment enriched with proinflammatory T cell phenotypes and impaired regulatory T cell function. These findings suggest that Tregs are both targets and potential biomarkers of ustekinumab response, with their phenotypic and transcriptional features providing insight into mechanisms of therapeutic resistance. Ustekinumab may directly target mucosal regulatory T cells, and lack of response to this therapy is related to the inability of these cells to properly carry out their function of suppressing inflammation.
Briggs KC, Tam A, Chaaban L, Luo A, Kobeissi L, Lazarev M, Parian A, Chowdhury R, Selaru FM, Casella K
Sphingosine 1-Phosphate (S1P) Receptor Modulators as an Induction and Maintenance Therapy for Moderate to Severe Ulcerative Colitis: A Systematic Review and Meta-analysis of Randomized Controlled Trials.Review Digestive diseases and sciences | 2026-04-13
Sphingosine-1-phosphate receptor (S1PR) modulators have emerged as a novel therapeutic class for ulcerative colitis (UC), yet their overall efficacy and safety across clinical trials have not been comprehensively evaluated. This meta-analysis assesses the impact of S1PR modulators on clinical, endoscopic, and histological outcomes in UC. A systematic search of PubMed, CENTRAL, Google Scholar, and ClinicalTrials.gov was conducted through November 20, 2025. Randomized controlled trials evaluating S1PR modulators in adults with UC were included. Risk of bias was assessed using the RoB 2 tool, and pooled estimates were calculated using a random-effects model. Eight trials involving 2663 participants were included. Analysis comparing S1PR modulators with placebo included etrasimod, ozanimod, tamuzimod, and KRP203. S1PR modulators significantly improved clinical response during induction (RR 2.47; p < 0.00001) and maintenance (RR 3.30; p = 0.0002). Clinical remission was also significantly increased in both the induction (RR 1.84; p < 0.00001) and maintenance phases (RR 2.20; p = 0.0001). Endoscopic improvement was significantly enhanced during induction (RR 2.32; p < 0.00001) and remained significant in maintenance (RR 1.95; p = 0.03). Histological remission improved significantly in both induction (RR 2.59; p < 0.00001) and maintenance (RR 2.60; p < 0.00001). Mucosal healing was significantly increased in the induction (RR 2.54; p < 0.00001) and maintenance phases (RR 2.21; p < 0.00001). Adverse events were slightly increased with S1PR modulators (RR 1.13; p = 0.002), while serious adverse events (p = 0.73) and discontinuations (p = 0.67) did not differ significantly from placebo. S1PR modulators demonstrate robust efficacy during the induction phase across all key clinical and tissue-based outcomes, with more modest or variable effects during maintenance. Their safety profile remains acceptable, supporting their role as a promising therapeutic option for UC.
Gardezi SAA, Iqbal MJ, Ulhaq S, Albustanji Q, Saleh A, Sajjad ZB, Shahzad M
Pickering emulsion as an oral delivery platform of anti-TNF-α antibody for ulcerative colitis therapy. International journal of pharmaceutics | 2026-04-13
Monoclonal antibodies that block pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) are effective therapy for inflammatory bowel diseases (IBD). However, intravenous infusion (IV), the standard route of administration of anti-TNF-α monoclonal antibodies (TNF-Ab), is time-consuming and inconvenient for patients. Recently, subcutaneously administered TNF-Ab formulations were developed for at-home injections of maintenance doses, but self-injection using needle-based pen systems can lead to low patient compliance. Therefore, an oral TNF-Ab formulation could significantly increase the medication adherence and quality of life of IBD patients. In this work, we developed a patient-friendly formulation based on a casein-stabilized Pickering emulsion for oral delivery of TNF-Ab (Casein-PE@TNF-Ab). Pickering emulsion was employed to protect TNF-Ab from gastric degradation and enhance colon residence time. Casein-PE@TNF-Ab exhibited a uniform particle size of 300 nm, a zeta potential of -45 mV, and encapsulation efficiency above 80%. In vitro studies showed enhanced uptake of Casein-PE@TNF-Ab by lipopolysaccharide-stimulated RAW264.7 macrophages compared with non-stimulated cells. In vivo imaging demonstrated prolonged colonic retention relative to free TNF-Ab. In DSS-induced colitis mice, oral Casein-PE@TNF-Ab markedly increased colon length and suppressed colonic TNF-α, IL-1β, and MPO levels by 82%, 61%, and 62%, respectively, versus DSS. Neutrophil infiltration in the colon also decreased by 46% relative to DSS group. The formulation remained stable for 3 months at 4 °C with preserved particle size and TNF-α-neutralizing activity. Together, these findings indicate that casein-stabilized Pickering emulsions provide a promising oral platform for antibody delivery and represent a viable strategy for ulcerative colitis therapy.
Xie J, Funk GA, Song SJ, Li X, Ahlquist CSE, Villela-Nava AL, Kim H
Adverse Events Related to Azathioprine Use in Patients With Inflammatory Bowel Disease: A Real-World Cohort Study. Gastroenterology research and practice | 2026-04-10
Azathioprine is one of the commonly used maintenance therapies in patients with inflammatory bowel disease (IBD), specifically in low- and middle-income countries. However, the use of thiopurines is questioned due to safety concerns. We aimed to assess the adverse event (AE) profile of azathioprine in IBD patients. This was a single-centre retrospective study. All the consecutive patients treated with azathioprine were considered for this study. Data were collected from prospectively maintained IBD files. The primary objective was to assess the adverse events arising due to azathioprine use. The AEs were defined as per standard definitions. The relation between the AE and dose and duration of azathioprine use was assessed. Among 48 patients [UC: 20 (41.7%) and CD: 28 (58.3%)] included, 30 (62.5%) were male. The mean age and the disease duration were 41.2 ± 15.7 years and 15 (5-40.5) months, respectively. The initiation and maximum dose of azathioprine were 0.91 ± 0.15 and 2.04 ± 0.58 mg/kg. The median thiopurine treatment duration was 6.5 (2.25-15), 11.5 (3.5-23.5) and 5.75 (2-12.5) months, respectively, in the whole cohort, UC and CD. A total of 25 (52.1%) patients developed adverse events [8 (40.0%) in UC and 17 (60.7%) in CD]. The commonest AEs were leukopenia in 15 (31.2%), GI intolerance in 5 (10.4%), arthralgia in 4 (8.3%), hepatitis in 3 (6.2%) and hair fall in 2 (4.1%) patients. No infection or acute pancreatitis episode or malignancy was reported. A total of 16 (33.3%) patients stopped azathioprine. AEs were the most common cause of azathioprine withdrawal in 12 (25.0%). No serious adverse event was reported. Adverse events are common and lead to therapy discontinuation in one fourth of the IBD patients on azathioprine. The commonest adverse events are leukopenia, GI intolerance, arthralgia, hepatitis, and hair fall.
Ranjan MK, Neupane P, Maharjan B, Lamsal M, Poudel B
Harnessing Nanocarriers to Modulate Gut Inflammation: A New Era in IBD Management. Recent advances in inflammation & allergy drug discovery | 2026-04-09
Inflammatory bowel disease (IBD) is a chronic inflammatory condition affecting the gastrointestinal tract, primarily including Crohn’s disease and ulcerative colitis. Current treatments rely heavily on synthetic medications and monoclonal antibodies. While these are effective for some patients, they often cause serious side effects, incur high costs, and can lead to complications with long-term use. Consequently, there is growing interest in exploring alternative and complementary therapies. Natural biomolecules derived from plants and animals have demonstrated promising anti-inflammatory and immunomodulatory effects in both in vitro and in vivo studies, offering a potentially safer and more sustainable approach to managing IBD. Nanotechnology is driving significant progress in the diagnosis and treatment of IBD. With biosensors and advanced imaging agents, the disease can be detected and monitored more accurately, enabling earlier and more precise diagnoses. Additionally, nanoparticles are being extensively studied as drug delivery systems because they can improve targeted therapy, protect drugs from degradation, and reduce systemic toxicity. However, challenges remain, including premature drug release, limited targeting efficiency, and undesired immune reactions. Although several clinical trials are ongoing, only a few nanoparticle-based treatments have achieved successful outcomes. This review aims to highlight recent advances in nanoparticle-mediated diagnosis and therapy for IBD, emphasizing the opportunities, challenges, and future directions in this field.
Khurana M, Sharma S, Mahajan S, Lamba K, Chauhan S, Mehta S, Dhankhar S, Yasmin S
DOI: 10.2174/0127722708408084251209145952 | View on PubMed →
Cellulose nanocrystal stabilised Pickering emulgels for sustained colonic delivery of budesonide. Colloids and surfaces. B, Biointerfaces | 2026-04-06
Inflammatory Bowel Disease (IBD) is a chronic gastrointestinal condition that could benefit from targeted drug delivery strategies to minimise systemic side effects. Conventional therapies often lack site specificity, limiting their effectiveness. Here, emulgels stabilised by cellulose nanocrystals (CNC) and reinforced with α-cyclodextrin/polyethylene glycol (α-CD/PEG) supramolecular gels were explored as a novel platform for the local delivery of budesonide to the gastrointestinal tract. CNC-stabilised Pickering emulsions (40-70% v/v oil, 0.5-2 mg·mL⁻¹ CNC) were characterised for droplet size, zeta potential, stability, and rheology. Emulgels were obtained by incorporating α-CD (6-10% w/v) and PEG (5-10% w/v, 10 and 20 kg/mol) in the aqueous phase. These systems were assessed for long-term stability, rheological properties, drug release, mucoadhesion, cytocompatibility, and drug permeability in Caco-2 cell monolayers. Emulsions showed enhanced stability with increasing CNC concentration and oil fraction. Incorporating a gel phase of α-CD/PEG markedly increased the storage modulus, G’ up to 1.53 × 10⁵ Pa without phase separation over 30 days. The emulgels shear-thinned and quickly recovered after release of the strain, equally after injection through a synringe, and displayed mucoadhesiveness to porcine intestinal tissue. Budesonide was efficiently loaded (86-98%) and released in a sustained manner over 72 h. Permeation studies confirmed epithelial drug transport, which was reduced compared to solution, consistent with controlled release. The emulgels did not compromise epithelial barrier integrity and were non-toxic to Caco-2 cells. Overall, CNC-stabilised α-CD/PEG emulgels demonstrate high stability, biocompatibility, and tunable release, making them promising candidates for localised IBD therapy.
Akapan P, da Silva M, Abdillah Akbar BVEB, Alhnan MA, Vllasaliu D, Dreiss CA
[Association of Toll-like receptor 5 gene polymorphism with the clinical efficacy of ustekinumab in patients with Crohn’s disease]. Zhonghua yi xue za zhi | 2026-04
Objectives: To investigate the association of Toll-like receptor 5 (TLR5) gene polymorphisms with the clinical efficacy of ustekinumab (UST) in the treatment of Crohn’s disease (CD) patients. Methods: The patients with active CD who received UST treatment were retrospectively recruited from the Department of Gastroenterology, the Second Affiliated Hospital of Wenzhou Medical University between January 2022 and April 2025. The loci rs5744168 and rs5744174 in TLR5 gene were genotyped by multiplex polymerase chain reaction-ligase detection reaction technique. The clinical response of CD patients was evaluated by Harvey-Bradshaw index (HBI) at week 8 of follow-up. The patients were divided into the response group (a decline of HBI≥ 3 points compared with week 0) and the non-response group. The mucosal healing was assessed by the Simplified Endoscopic Score for Crohn’s disease (SES-CD) at week 32 of UST treatment. The patients were divided into the mucosal healing group (SES-CD≤2 points or absence of mucosal ulcerations) and the mucosal non-healing group. The distribution differences of TLR5 gene polymorphism were compared between the response group and the non-response group, as well as between the mucosal healing group and the mucosal non-healing group. The genotypes or alleles with distribution differences were included into unconditional logistic regression models to investigate the association between the gene polymorphisms of TLR5 and the clinical efficacy of UST treatment in CD patients. Results: A total of 198 CD patients were included (133 males, 65 females), with age of (32±12) years. There were 117 cases in the response group and 81 cases in the non-response group at week 8 of UST treatment. The homozygous variant genotype (GG) [1.7% (2/117) vs 11.1% (9/81), corrected P=0.024] and variant allele (G) [15.8% (37/234) vs 27.8% (45/162), corrected P=0.008] of locus rs5744174 in the response group were less frequent than those in the non-response group. The homozygous variant genotype (GG) (OR=0.17, 95%CI: 0.04-0.83, P=0.029) and variant allele (G) (OR=0.51, 95%CI: 0.31-0.85, P=0.010) of locus rs5744174 were shown to be associated with the clinical response at week 8. There were 79 cases in the mucosal healing group and 119 cases in the mucosal non-healing group at week 32 of UST treatment. The frequency of variant genotype (GA+AA) [15.2% (12/79) vs 1.7% (2/119), corrected P<0.001] and the frequency of variant allele (A) [9.5% (15/158) vs 0.8% (2/238), corrected P<0.001] of locus rs5744168 in mucosal healing group were higher than those in the mucosal non-healing group. The variant genotype (GA+AA) (OR=8.94, 95%CI: 1.88-42.50, P=0.006) and variant allele (A) (OR=9.54, 95%CI: 2.09-43.66, P=0.004) of locus rs5744168 were found to be related with the mucosal healing at week 32. Conclusions: Among the patients with active CD receiving UST treatment, the variation of locus rs5744174 in TLR5 gene may be associated with a reduced clinical response rate at week 8. However, the variation of locus rs5744168 may be linked to an increased mucosal healing rate at week 32. 目的： 探讨Toll样受体5（TLR5）基因多态性与乌司奴单抗（UST）治疗克罗恩病（CD）患者临床疗效的关系。 方法： 回顾性收集2022年1月至2025年4月于温州医科大学附属第二医院消化内科接受UST治疗的活动期CD患者。采用多重聚合酶链反应-连接酶检测反应技术检测TLR5基因rs5744168和rs5744174位点的基因型。CD患者随访至第8周时采用哈维-布拉德肖指数（HBI）评估临床应答情况，分为应答组（HBI较第0周下降≥3分）和无应答组。第32周时采用简化克罗恩病内镜评分（SES-CD）评估黏膜改善情况，分为黏膜愈合组（SES-CD≤2分或无溃疡）和黏膜未愈合组。比较应答组与无应答组、黏膜愈合组与黏膜未愈合组TLR5基因多态性的分布差异。将存在分布差异的基因型或等位基因分别纳入非条件logistic回归模型，分析TLR5基因多态性与UST治疗CD患者临床疗效的关系。 结果： 共纳入198例CD患者，男133例，女65例，年龄（32±12）岁。UST治疗第8周时，应答组117例，无应答组81例。应答组rs5744174位点的纯合子变异基因型（GG）频率［1.7%（2/117）比11.1%（9/81），校正P=0.024］和变异等位基因（G）频率［15.8%（37/234）比27.8%（45/162），校正P=0.008］均低于无应答组。rs5744174位点的纯合子变异基因型（GG）（OR=0.17，95%CI：0.040.83，P=0.029）和变异等位基因（G）（OR=0.51，95%CI：0.310.85，P=0.010）均与第8周临床应答相关。第32周时，黏膜愈合组79例，黏膜未愈合组119例。黏膜愈合组rs5744168位点的变异基因型（GA+AA）频率［15.2%（12/79）比1.7%（2/119），校正P<0.001］和变异等位基因（A）频率［9.5%（15/158）比0.8%（2/238），校正P<0.001］均高于黏膜未愈合组。rs5744168位点的变异基因型（GA+AA）（OR=8.94，95%CI：1.8842.50，P=0.006）和变异等位基因（A）（OR=9.54，95%CI：2.0943.66，P=0.004）均与第32周黏膜愈合相关。 结论： 接受UST治疗的CD患者中，TLR5基因rs5744174位点变异可能与第8周临床应答率降低相关，而rs5744168位点变异可能与第32周黏膜愈合率增高相关。.
Lu JH, Shao XX, Lin DP, Xu Y, Ma GL, Jiang Y
DOI: 10.3760/cma.j.cn112137-20250903-02288 | View on PubMed →
Impact of Immunogenicity on Clinical Outcomes in Patients With Moderate-to-Severe Inflammatory Bowel Disease Receiving Subcutaneous Infliximab: A Post Hoc Analysis of the LIBERTY Trials.RCT★ United European gastroenterology journal | 2026-04
LIBERTY-CD and LIBERTY-UC demonstrated superior efficacy of subcutaneous infliximab (IFX SC) to placebo in patients with Crohn’s disease (CD) or ulcerative colitis (UC). Here, we investigated the impact of anti-drug antibodies (ADAs) on clinical outcomes. Patients randomized to IFX SC maintenance treatment in the LIBERTY trials were included (CD, n = 231; UC, n = 294). ADAs were tested using a highly sensitive, drug-tolerant assay. Patients were grouped by ADA occurrence and titer and evaluated for outcomes up to Week (W) 54. Among patients with CD and UC, 150 (64.9%) and 187 (63.6%) were ADA-positive, respectively. No statistically significant differences were observed between the ADA-positive and ADA-negative groups in W54 efficacy (CD: clinical remission, 69.5% [95% confidence interval: 61.6-77.5] vs. 79.7% [70.2-89.2], p = 0.134; endoscopic response, 57.5% [48.9-66.1] vs. 65.2% [54.0-76.5], p = 0.359; UC: clinical remission, 49.1% [41.3-56.8] vs. 57.0% [46.5-67.4], p = 0.284), drug persistence (CD: 84.7% [79.1-90.6] vs. 85.2% [77.8-93.3]; UC: 84.5% [79.5-89.8] vs. 77.6% [70.1-85.9]), and safety (patients with ≥ 1 treatment-emergent adverse event; CD: 71.2% [64.0-78.3] vs. 74.4% [64.9-83.8]; UC: 69.5% [62.9-76.0] vs. 64.2% [55.0-73.3]), despite lower drug concentrations in ADA-positive patients at W54 (CD: 10.6 μg/mL [9.1-12.2] vs. 17.9 μg/mL [15.8-20.1]; UC: 12.2 μg/mL [10.8-13.5] vs. 21.0 μg/mL [18.4-23.6]). No significant relationship between ADA titer and efficacy or persistence was noted. Although ADAs affected drug levels, no significant differences by ADA occurrence were observed in W54 efficacy or safety among patients receiving IFX SC maintenance treatment. While high ADA titers were associated with lower drug levels, effectiveness was not diminished within 1 year. ClinicalTrials.gov identifiers NCT03945019 (LIBERTY-CD) and NCT04205643 (LIBERTY-UC).
Colombel JF, Danese S, Schreiber S, Sands BE, Yarur AJ, Kang A, Kim DH, Lee YN, Hanauer SB
Microbiome & Immunology (12 papers)
Clinical benefit of faecal microbiota transplantation administered via a single retention enema as an adjunctive treatment in dogs with chronic enteropathy: a randomised controlled trial. The Journal of small animal practice | 2026-04-17
To evaluate the clinical benefit of faecal microbiota transplantation administered via a single retention enema, as an adjunctive treatment in the management of dogs with chronic enteropathy. Blinded, randomised controlled trial. Dogs with chronic enteropathy (>3 weeks of small or mixed intestinal diarrhoea) were randomly allocated to either the faecal microbiota transplantation or standard treatment group (ratio 1:1) via blinded selection. Dogs in the standard treatment group had a diet change only, while dogs in the faecal microbiota transplantation group had a diet change and faecal microbiota transplantation. faecal microbiota transplantation was performed using fresh faecal material from donor dogs, screened for selected enteropathogens and administered via retention rectal enema. Outcomes measured included the Canine Inflammatory Bowel Disease Activity Index, faecal score and the owner’s reported improvement. Group comparisons were made using Fisher’s exact tests (owner-reported outcomes) and Kruskal-Wallis tests adjusted for ties (Canine Inflammatory Bowel Disease Activity Index and faecal score). Forty-two dogs with chronic enteropathy (median Canine Inflammatory Bowel Disease Activity Index score 6 [range 4 to 11]) were included in the study. Twenty-five dogs were randomly assigned to receive faecal microbiota transplantation, while 17 dogs were allocated to standard treatment. A progressive improvement in stool consistency (reduced faecal score) was recorded over time for most dogs in both groups. By Day 90, the rates of owner-defined clinical improvement were 76% (CI 54% to 90%) in the faecal microbiota transplantation group and 73% (CI 40% to 92%) in the standard treatment group. No significant differences were evident between the two groups based on the proportion of owners that reported clinical improvement, Canine Inflammatory Bowel Disease Activity Index score or faecal score. This study did not demonstrate a clear clinical benefit for adjunctive faecal microbiota transplantation via single retention enema in dogs with chronic enteropathy compared to diet change alone, although the small sample size means that a type II error cannot be excluded. The similar outcome for both groups supports high rates of food responsiveness among this cohort of chronic enteropathy dogs.
Allerton F, Whittle MJ, Durkin L, Prior C, Trehy M, Swales H, Duplan F, Borgonovi S, Pinchbeck G, Gajanayake I
Fufang Tongye Shaoshang You repairs ulcerative colitis in mice caused by DSS based on the balanced strategy of “inflammation inhibition-microbiota regulation-mucosa protection”. Journal of ethnopharmacology | 2026-04-15
Ulcerative colitis (UC) is a complex inflammatory bowel disorder characterized by immune dysregulation, intestinal barrier dysfunction, and intestinal microbiota imbalance. Current therapies remain limited, highlighting the need for alternative strategies. Fufang Tongye Shaoshang You (TYY), a traditional ethnomedicine historically used for diarrhea and ulcers, exhibits promising therapeutic potential against UC. This study aims to evaluate the therapeutic efficacy of TYY in UC mice and to systematically elucidate its underlying mechanisms and potential bioactive constituents. A dextran sulfate sodium (DSS)-induced UC mouse model was established to evaluate the reparative effect of TYY by assessing disease activity, colon length, and histopathology. Systemic effects were examined through spleen index and serum markers of liver and kidney function. Key UC-associated targets were identified via analysis of GEO transcriptomic datasets. The anti-inflammatory and barrier-protective mechanisms of TYY were explored using a series of molecular and histological techniques. Intestinal microbiota changes were analyzed with 16S rRNA gene sequencing. Furthermore, serum pharmacochemistry (UPLC-Q-TOF-MS) identified and prioritized circulating components, which were validated in a lipopolysaccharide (LPS)-stimulated Caco-2 cell model for their regulatory effects in vitro. TYY exerted comprehensive therapeutic effects on UC by inhibiting IL-17 signaling pathway, rebalancing intestinal microbiota, and protecting intestinal mucosa, while also improving DSS-induced liver, kidney, and spleen dysfunction. Seven key bioactive components were identified as the primary pharmacodynamic substances responsible for TYY’s efficacy. This work systematically elucidates the multi-target mechanism of TYY in treating UC, demonstrating that its therapeutic efficacy arises from a balanced strategy encompassing inflammation inhibition, microbiota regulation, and mucosa protection-showing demonstrable superiority over its vehicle alone and being friendly to extra-intestinal organs. The identification of seven bioactive components and their differential targeting of the IL-17 signaling network provides a mechanistic foundation for repurposing this topical ethnomedicine as a promising oral complementary therapy for UC.
Lu Y, Dai Y, Duan Y, Ni X, Li J, Wang Q, Cai P, Li S
Amelioration of colitis through restored gut ecology using Christensenella intestinihominis AF73-05CM02 as a probiotic in mice. Communications biology | 2026-04-14
Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), is closely linked to gut microbial imbalance marked by loss of beneficial microbes and overgrowth of pathogens. Christensenella intestinihominis, a bacterium that associated with intestinal homeostasis, is depleted in patients with ulcerative colitis (UC), yet its therapeutic potential against this disease remains to be elucidated. Here we demonstrate that C. intestinihominis AF73-05CM02, a strain isolated from Chinese individual, alleviates colitis. In healthy human gut, C. intestinihominis co-occurs with beneficial microbes in strongly connected networks, while these interactions are disrupted in UC. We employ the dextran sulfate sodium (DSS)-induced murine colitis model, a widely recognized preclinical model for investigating intestinal inflammation. In this model, oral gavage with AF73-05CM02 mitigates weight loss, ameliorates colonic injury, improves intestinal health markers, and reverses colon damage. It exerts these effects by reducing harmful bacteria such as Helicobacter species and increasing beneficial taxa like Akkermansia, while enhancing the intestinal epithelial barrier integrity and regulating immune responses. These findings indicate AF73-05CM02 may aid in the treatment of inflammatory bowel disease by restoring a healthy gut microbial community.
Wu Z, Sun X, Li X, Wang H, Liang H, Wang M, Yang Z, Zhao K, He N, Xiao L
Clinical response and risk factors of fecal microbiota transplantation in children: a systematic review and meta-analysis.Meta-analysis European journal of pediatrics | 2026-04-14
The objective of this study is to investigate the clinical response and incidence of adverse events (AEs) following fecal microbiota transplantation (FMT) in children, across various diseases, populations, and treatment protocols. A systematic search was conducted across eight major Chinese and English databases, identifying 47 studies up to August 28, 2025, for inclusion. Study quality was assessed using the Quality Assessment with Diverse Studies (QuADS) tool. Single-arm rates were pooled via meta-analysis employing the Freeman-Tukey double arcsine transformation, followed by extensive subgroup comparisons to identify influencing factors. FMT demonstrated efficacy in pediatric recurrent Clostridium difficile infection (rCDI), inflammatory bowel disease (IBD), and autism spectrum disorder (ASD), although a higher incidence of AEs was observed in children with IBD. Subgroup analyses revealed that the use of donor feces from relatives or friends was associated with a higher clinical response rate in rCDI. The presence of comorbidities such as IBD diminished the response rate in rCDI patients. Younger age in rCDI and IBD patients showed a trend towards higher clinical response rates, though this did not reach statistical significance. No statistically or clinically significant differences were found in other subgroup comparisons. Meta-regression suggested IBD to be a risk factor for FMT-related AEs. This study innovatively delineates the efficacy-safety profile of pediatric FMT and outlines a pathway for optimizing individualized treatment regimens, providing crucial evidence-based guidance for clinical practice. This study has been registered on the PROSPERO database (CRD42024614196). • Fecal Microbiota Transplantation (FMT) demonstrates preliminary therapeutic potential in several pediatric diseases. • Existing evidence remains fragmented, with limited systematic data on factors modifying efficacy and safety in children. • The study revealed FMT’s high efficacy across rCDI, IBD, and ASD, and identified IBD as a risk factor for elevated FMT-related adverse events in pediatric patients. • Notably, related/friend donors improved rCDI response rates, while comorbidities like IBD reduced rCDI treatment efficacy.
Liu J, Sun X, Yuan P, Qin Y, Wu W, Fan Y, Zhang Y, Zou L, Ren C, Li S
Peptidomics: A New Dimension in Microbiome Research. Protein and peptide letters | 2026-04-10
The human gut microbiome is now recognised as a major determinant of health, with roles extending beyond digestion to influence neurodegeneration, metabolism, immunity, and pharmacological responses. Clinical studies link microbial imbalances to Alzheimer’s disease, Parkinson’s disease, depression, and cardiovascular disorders, yet the underlying mechanisms remain only partly understood. Methodological advances have progressively deepened our insight. DNA-based sequencing (metagenomics) catalogues microbial genes but reveals only potential functions. RNA-based sequencing (metatranscriptomics) highlights active gene expression, but instability of transcripts and poor correlation with protein activity limit its predictive value. Metabolomics measures small-molecule end products, providing direct evidence of microbial biochemistry and identifying disease-linked metabolites such as urolithin A, trimethylamine N-oxide, and equol. These approaches together have transformed microbiome science, but they remain incomplete. A critical and underutilised dimension is peptidomics: the systematic analysis of endogenous peptides in the gut and circulation. Enabled by peptide-enriching, protease-inhibiting workflows and high-resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS), peptidomics directly captures unstable signaling peptides and proteolytic fragments that are often invisible to conventional proteomics. Coupled with emerging gut-specific peptide databases, such as MetaPep, and Artificial Intelligence (AI) assisted de novo sequencing and spectral prediction for non-human peptides, this provides a concrete technical route to reading out the functional peptide layer of the microbiome. Peptidomics can capture functional signals of host-microbiome interaction, reveal context-specific biomarkers, and provide mechanistic insight into disease. Recent studies demonstrate that peptide-level resolution uncovers microbial contributions to gut inflammation, modulates the gut-brain axis, and enables peptide-based disease stratification in conditions such as inflammatory bowel disease. However, despite these promising examples, peptidomics remains largely absent from mainstream microbiome research, which needs to be changed. Integrating peptidomics with existing genomic, transcriptomic, and metabolomic approaches will generate a more complete and functional picture of the microbiome. This shift will accelerate biomarker discovery, refine diagnostics, and expand the search for peptide-based therapeutics, positioning peptidomics as an essential next step in microbiome science.
Hilpert K
DOI: 10.2174/0109298665436241260327111926 | View on PubMed →
A novel Curcuma wenyujin-derived fructan modulates gut microbiota and metabolic pathways to ameliorate DSS-induced colitis. Carbohydrate polymers | 2026-04-06
Ulcerative colitis (UC) involves epithelial barrier breakdown, dysregulated mucosal immunity, and dysbiosis of the gut microbiota (GM). Given the biotherapeutic potential of dietary fructans, this study aimed to isolate a neutral fructan (CWP-W-1) from Curcuma wenyujin and to characterize its chemical structure and anti-colitis effects. CWP-W-1 was purified by DEAE-Sepharose and gel-filtration chromatography. Its structure was established using HPGPC, monosaccharide profiling, FT-IR, GC-MS, and NMR. In a DSS-induced UC mouse model, CWP-W-1 treatment alleviated disease severity and weight loss, decreased the disease activity index and rectal bleeding, prevented colon shortening, and restored histological architecture, with increased goblet cells and mucin staining. Metagenomic sequencing showed that CWP-W-1 mitigated DSS-associated dysbiosis, recovering α-diversity and shifting β-diversity toward healthy controls, with decreases in Proteobacteria and enrichment of beneficial taxa. Metabolite analyses indicated that CWP-W-1 increased short-chain fatty acids (SCFAs) and remodeled the tryptophan metabolic pathway, shifting the pro-inflammatory kynurenine bias toward indole-derived aryl hydrocarbon receptor (AhR) ligands, consistent with epithelial barrier support and immune homeostasis. Collectively, these results demonstrated that CWP-W-1 was a structurally defined fructan with significant therapeutic potential for UC through coordinated modulation of barrier function, mucosal immunity, and the gut microbiota.
Li Z, Li Z, Chu L, Hu S, Xue C, Lin H, Luo Y, Zhang Y, Zhang J, Wang Z
The interplay between probiotics and mast cells in gut inflammation: a mini-review.Review Frontiers in cellular and infection microbiology | 2026-04-01
Mast cells (MCs) are myeloid-derived immune cells that differentiate in peripheral tissues, where they are strategically located near epithelial surfaces. In the gastrointestinal tract, MCs regulate immune response through the release of mediators such as histamine, cytokines, and proteases; however, their excessive activation promotes inflammation, increases intestinal permeability, and contributes to disorders such as food allergies, inflammatory bowel disease, and chronic intestinal inflammation. Probiotics are live microorganisms that confer health benefits to the host when administered in adequate amounts and play a key role in gut immune regulation by modulating the microbiota, reinforcing epithelial barrier integrity, and promoting anti-inflammatory responses. Although MCs and probiotics have been extensively studied independently, their functional interplay in gut health and disease remains poorly defined. Here, we propose that probiotic-mast cell interactions represent an underexplored immunoregulatory axis in intestinal homeostasis. This mini-review synthesizes current evidence on the crosstalk between probiotics and MCs, highlighting the limited mechanistic understanding of these interactions and its potential therapeutic implications.
Herrera-Saldivar MF, Hernandez-Bautista NC, Quiroga-Garza JM, Vazquez-Guillen JM, Chacon-Salinas R, Rojas-Contreras M, Vazquez-Juarez R, Resendez-Perez D, Tamez-Guerra RS, Rodriguez-Padilla C
Functional changes in the gut microbiota are associated with the intestinal phenotype in A20 haploinsufficiency. Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology | 2026-04
A20 haploinsufficiency (HA20) is an autoinflammatory disease driven by pathogenic variants in TNFAIP3, which plays a crucial role in regulating immune responses. The clinical manifestations of HA20 resemble those of inflammatory bowel disease (IBD), with prominent gastrointestinal (GI) involvement. Given the well-established association between gut microbiota alterations and IBD, this study aimed to describe the GI involvement of HA20 patients and to investigate their fecal microbiota using shotgun sequencing and metabolomics. This study included 16 HA20 patients and 22 healthy age and sex-matched controls. GI clinical phenotype, liver imaging, and liver and GI tissue histology were assessed. Shotgun metagenomic sequencing was performed on fecal DNA. Fecal metabolomic profiling of bile acids, short-chain fatty acids (SCFAs), and tryptophan metabolites was performed. Liver imaging revealed chronic liver disease in 3/5 patients, showing as liver dysmorphia and portal hypertension. Histological analysis showed lymphoplasmocytic infiltrate of the GI tract and the liver. The fecal microbiota of HA20 patients was characterized by marked alterations, including a reduction in microbial diversity and an increase in the pro-inflammatory bacterium Ruminococcus gnavus. Microbial bile acid deconjugation and desulfation were impaired. Additionally, tryptophan metabolism was altered, with a shift towards the kynurenine pathway. Our results show that HA20 is associated with gut microbiota alterations and significant disruptions in metabolic pathways, particularly involving bile acids. These alterations could contribute to the chronic inflammation observed in HA20. These findings highlight the role of the gut-liver axis and of mucosal barrier dysfunction in HA20.
Elhani I, Bredon M, Enea D, Desmons A, Arrive L, Bazille C, Lefevre A, Aouba A, Bigot A, de Moreuil C
[Overview of the relevance of the intestinal mucus layer of the intestinal barrier - current state of knowledge and clinical perspective].Review MMW Fortschritte der Medizin | 2026-04
The intestinal mucus layer constitutes an essential component of the gut barrier and plays a pivotal role in gastrointestinal health. Disruptions of this layer, particularly due to dietary fiber deficiency and mucus degrading bacteria, have been associated with various disorders including irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), food intolerances, and other related conditions. While research on gastrointestinal microbiota has garnered significant attention, the knowledge of the mucus layer remains comparatively understudied. This review synthesizes current knowledge regarding the mucus layer and evaluates its clinical relevance for both the pathogenesis and therapeutic management of intestinal disorders, as well as their prevention. An intact mucus layer provides critical protection against pathogenic factors while promoting microbiota homeostasis and functionality. Conversely, fiber deficiency accelerates mucus layer degradation, increases intestinal permeability, and promotes inflammatory processes. Therapeutic interventions such as dietary fibers, prebiotics, and postbiotics (e.g., short-chain fatty acids, SCFAs) demonstrate potential to restore mucus layer integrity and reinforce intestinal barrier function. The intestinal mucus layer represents an underappreciated yet crucial factor in intestinal health and disease pathogenesis. Fiber supplementation and postbiotic administration emerge as key therapeutic strategies for mucus layer reinforcement and regeneration. Further research is warranted to develop disease- and symptom-specific mucus-targeted therapies, including refined post- and prebiotic based therapeutic approaches. Hintergrund: Die intestinale Mukusschicht ist ein essenzieller Bestandteil der Darmbarriere und spielt eine zentrale Rolle für die Darmgesundheit. Störungen dieser Schicht, insbesondere durch Ballaststoffmangel und mukusabbauende Bakterien, werden mit Erkrankungen wie dem Reizdarmsyndrom, chronisch entzündlichen Darmerkrankungen, Nahrungsmittelintoleranzen und weiteren Erkrankungen in Verbindung gebracht. Während das Wissen um das gastrointestinale Mikrobiom hohe Aufmerksamkeit erfährt, sind Kenntnisse über die Mukusschicht noch wenig verbreitet.Zielsetzung: Diese Übersichtsarbeit fasst den aktuellen Wissensstand zur intestinalen Mukusschicht zusammen und beleuchtet ihre klinische Relevanz für die Pathogenese und Therapie von Darmerkrankungen sowie deren Prävention. Ergebnisse: Eine intakte Mukusschicht schützt vor pathogenen Einflüssen und unterstützt das Gleichgewicht und die Funktion der intestinalen Mikrobiota. Ballaststoffmangel wiederum fördert den Abbau der Mukusschicht, erhöht die Darmpermeabilität und begünstigt Entzündungen. Therapeutische Ansätze wie Ballaststoffe, Präbiotika und Postbiotika (z. B. mit kurzkettigen Fettsäuren, SCFA) können die Mukusschicht regenerieren und die Darmbarriere stärken. Schlussfolgerungen: Die intestinale Mukusschicht ist ein bislang wenig beachteter Schlüsselfaktor für Darmerkrankungen und Darmgesundheit. Ballaststoffe und Postbiotika sind wesentliche therapeutische Maßnahmen zur Stärkung und Regeneration der Mukusschicht. Die Erweiterung des Wissensstandes über zukünftige Krankheits- und symptomspezifische Mukustherapien, beispielsweise durch differenziertere Post- und Präbiotika, ist notwendig. Schlüsselwörter: Darmbarriere, Mikrobiom, MukusschichtEingereicht am 3. Dezember 2025 – Revision akzeptiert am 5. Januar 2026.
Storr M, Burghard A
[Study on the effect of high-intensity interval exercise on ulcerative colitis in mice]. Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] | 2026-04
Objective: This study aims to systematically explore the protective effect and its underlying mechanism of high-intensity interval exercise (HIE) on the mouse model of ulcerative colitis (UC) induced by dextran sulfate sodium (DSS) through regulating the structure and function of gut microbiota. Methods: A simple randomized controlled allocation method was adopted. From July to August 2024, 24 male C57BL/6 mice were divided into the control group (Con), ulcerative colitis group (DSS), high-intensity interval exercise group (HIE), and high-intensity interval exercise-ulcerative colitis group (HIE-DSS) in the experimental animal room of the Second Department of Infectious Disease Prevention and Control in the Disease Prevention and Control Center of the Eastern Theater Command, with six mice in each group. During the experimental stage, the mice in the HIE and HIE-DSS groups first received 5-week high-intensity interval exercise training. Then, the mice in the DSS and HIE-DSS groups were given free access to a 3% DSS solution for 7 days to induce the UC model. The diarrhea status, body weight changes of the mice were observed, and the colon length was measured. The histopathology and morphology of the colon tissues were scored. H&E staining was used to observe the pathological changes in the colon tissues. An enzyme-linked immunosorbent assay (ELISA) was used to analyze the expression levels of interleukin (IL) IL-10, IL-1β, IL-6 and tumor necrosis factor-α (TNF-α) in the peripheral serum of the mice in each group. Real-time fluorescent quantitative PCR (qRT-PCR) was used to monitor the changes in the levels of IL-1 mRNA, IL-6 mRNA, IL-10 mRNA, and TNF-α mRNA in the mouse colon tissues. Kits were used to detect the changes in malondialdehyde (MDA), myeloperoxidase (MPO), catalase (CAT), glutathione (GSH), total superoxide dismutase (T-SOD), and reactive oxygen species (ROS) in the mouse colon tissues. 16S rRNA sequencing and gas chromatography-mass spectrometry (GC-MS) techniques were used to detect the changes in the gut microbiota and fecal metabolites. Immunohistochemical techniques and bacterial translocation experiments were used to evaluate the changes in the gut mucosal proteins Occludin and Muc2 and the gut barrier function. One-way analysis of variance (One-way ANOVA) was used for statistical analysis. Newman-Keuls multiple comparison test was used to evaluate the differences between groups. Results: The weight changes (g) of the Con group, DSS group, HIE group, and HIE-DSS group were (28.29±0.71), (23.71±0.67), (27.61±1.20), and (25.63±0.78) respectively; the colon lengths (cm) were (7.67±0.41), (4.87±0.18), (7.08±0.22), and (6.53±0.14) respectively; the morphological scores of colon tissues were (1.26±0.62), (2.01±0.41), (1.25±0.70), and (1.57±0.28) respectively; the pathological scores were (0.66±0.31), (1.33±0.42), (0.81±0.19), and (1.03±0.32) respectively. The weight change, colon length, colon morphological score, and colon tissue pathological score of the DSS group were significantly lower than those of the HIE-DSS group, with statistically significant differences (t=3.195, P=0.036), (t=4.478, P=0.008 6), (t=3.745, P=0.007 1), and (t=4.106, P=0.006 9).The contents of IL-1β (pg/ml) in the serum of the Con group, DSS group, HIE group, and HIE-DSS group were 19.10±0.89, 26.26±1.86, 221.65±1.43, and 22.46±1.54 respectively; the expression levels of IL-6 (pg/ml) were 30.82±7.15, 71.90±14.42, 28.70±6.62, and 37.40±4.58 respectively; the expression levels of TNF-α (pg/ml) were 22.78±6.11, 37.86±7.12, 24.68±4.07, and 27.75±6.32 respectively; the expression levels of IL-10 (pg/ml) were 59.13±9.02, 43.38±6.72, 53.17±5.27, and 51.92±4.18 respectively. Compared with the Con group, the expression levels of IL-1β, IL-6, and TNF-α in the serum of the DSS group were significantly increased, while the expression level of IL-10 was significantly decreased, with statistically significant differences (t=6.345, P=0.044), (t=5.115, P=0.038), (t=8.931, P=0.021), (t=6.612, P=0.039). The expression levels of IL-1β, IL-6, and TNF-α in the HIE-DSS group were significantly lower than those in the DSS group, while the expression level of IL-10 was significantly higher, with statistically significant differences (t=7.749, P=0.000 8), (t=5.327, P=0.007 4), (t=10.140, P=0.000 6), (t=7.718, P=0.000 5).The relative expression levels of ROS (U/mol) in the colon tissues of the Con group, DSS group, HIE group, and HIE-DSS group were 111.83±10.90, 185.16±25.56, 118.83±16.43, and 135.83±11.81 respectively; the expression levels of MPO (U/mgport) were 0.71±0.85, 2.76±0.62, 0.90±0.43, and 1.56±1.33 respectively; the expression levels of CAT (U/mgport) were 0.44±0.31, 0.08±0.21, 0.37±0.25, and 0.30±0.22 respectively; the expression levels of MDA (nmol/mgport) were 0.38±0.12, 0.92±0.22, 0.46±0.18, and 0.57±0.19 respectively; the expression levels of GSH (mg/port) were 17.80±6.12, 6.11±2.82, 14.71±4.18, and 12.28±5.011 respectively; the expression levels of T-SOD (U/mgport) were 3.69±2.12, 1.25±0.61, 3.23±0.55, and 2.73±0.47 respectively. Compared with the HIE-DSS group, the expression levels of ROS, MPO, and MDA in the colon of the DSS group were significantly increased, while the expression levels of CAT, GSH, and T-SOD were significantly decreased, with statistically significant differences (t=3.915, P=0.005 4), (t=4.543, P=0.000 4), (t=8.018, P=0.000 7), (t=12.510, P=0.000 6), (t=6.703, P=0.000 5), (t=5.784, P=0.000 8).The expression levels (IOD) of tight-junction protein Muc2 in the colon tissues of the Con group, DSS group, HIE group, and HIE-DSS group were 3 019.51±23.26, 2 080.25±11.18, 2 690.32±17.24, and 2 473.50±16.04 respectively; the expression levels (IOD) of Occludin were 2 881.04±12.07, 2 198.30±10.05, 2 720.30±14.02, and 2 680.30±11.23 respectively. The expression levels of Muc2 and Occludin in the DSS group were significantly lower than those in the HIE-DSS and Con groups, with statistically significant differences (t=8.743, P=0.000 7), (t=9.634, P=0.000 9). Conclusion: As an emerging exercise mode, high-intensity interval training may participate in alleviating the pathogenesis of ulcerative colitis by regulating gut microbiota and their metabolites. 目的： 旨在探讨高强度间歇运动（HIE）通过调节肠道菌群结构与功能，对葡聚糖硫酸钠（DSS）诱导的小鼠溃疡性结肠炎（UC）模型的保护效应及其潜在机制。 方法： 采取简单随机对照分配方式，于2024年7—8月在东部战区疾病预防控制中心传染病防控二科实验动物房将24只雄性C57BL/6小鼠分为对照组（Con）、溃疡性结肠炎组（DSS）、高强度间歇运动组（HIE）和高强度间歇运动-溃疡性结肠炎组（HIE-DSS），每组各6只。在实验阶段，HIE组与HIE-DSS组小鼠首先接受为期5周的高强度间歇运动训练，之后对DSS组和HIE-DSS组小鼠采用3%DSS溶液自由饮用7 d，以诱导UC模型。观察小鼠腹泻情况、体重变化并测量结肠长度。对结肠组织病理学和形态学进行评分；采用苏木精-伊红（H&E）染色观察结肠组织病理变化；采用酶联免疫吸附试验（ELISA）分析各组小鼠外周血清中白介素（IL）的IL-10、IL-1β、IL-6和肿瘤坏死因子-α（TNF-α）的表达水平；采用实时荧光定量PCR（qRT-PCR）监测小鼠结肠组织中IL-1 mRNA、IL-6 mRNA、IL-10 mRNA和TNF-α mRNA水平的变化；采用试剂盒检测小鼠结肠组织丙二醛（MDA）、髓过氧化物酶（MPO）、过氧化氢酶（CAT）、谷胱甘肽（GSH）、超氧化物歧化酶（T-SOD）和活性氧（ROS）的变化；采用16S rRNA测序和气相色谱-质谱联用（GC-MS）技术检测肠道菌群和粪便代谢物的变化。采用免疫组化技术和细菌移位实验评估肠道黏膜蛋白Occludin和Muc2及肠道屏障功能变化。采用单因素方差分析（One-way ANOVA）进行统计学分析。组间差异的评估使用Newman-Keuls多重比较检验。 结果： Con组、DSS组、HIE组、HIE-DSS组体重（g）变化分别为（28.29±0.71）、（23.71±0.67）、（27.61±1.20）、（25.63±0.78）；结肠长度（cm）分别为（7.67±0.41）、（4.87±0.18）、（7.08±0.22）、（6.53±0.14）；结肠组织形态学评分（score）分别为（1.26±0.62）、（2.01±0.41）、（1.25±0.70）、（1.57±0.28）；病理评分（score）分别为（0.66±0.31）、（1.33±0.42）、（0.81±0.19）、（1.03±0.32）。DSS组体重变化、结肠长度、结肠形态学评分、结肠组织病理评分均较HIE-DSS组显著降低，差异有统计学意义（t=3.195，P=0.036）、（t=4.478、P=0.0086）、（t=3.745、P=0.0071）、（t=4.106，P=0.0069）。Con组、DSS组、HIE组、HIE-DSS组血清中IL-1β含量（pg/ml）分别为19.10±0.89、26.26±1.86、221.65±1.43、22.46±1.54，IL-6表达量（pg/ml）分别为30.82±7.15、71.90±14.42、28.70±6.62、37.40±4.58，TNF-α表达量（pg/ml）分别为22.78±6.11、37.86±7.12、24.68±4.07、27.75±6.32，IL-10表达量（pg/ml）分别为59.13±9.02、43.38±.6.72、53.17±.5.27、51.92±4.18。与 Con组相比，DSS组血清中IL-1β、IL-6、TNF-α表达显著升高，IL-10表达显著降低，差异有统计学意义（t=6.345，P=0.044）、（t=5.115，P=0.038）、（t=8.931，P=0.021）、（t=6.612，P=0.039）；HIE-DSS组IL-1β、IL-6、TNF-α表达较DSS组显著下降，IL-10表达显著上升，差异有统计学意义（t=7.749，P=0.000 8）、（t=5.327，P=0.007 4）、（t=10.140，P=0.000 6、（t=7.718，P=0.000 5）。Con组、DSS组、HIE组、HIE-DSS组的结肠组织中ROS相对表达量（U/mol）分别为111.83±10.90、185.16±25.56、118.83±16.43、135.83±11.81，MPO表达量（U/mgport）分别为0.71±0.85、2.76±0.62、0.90±0.43、1.56±1.33，CAT表达量（U/mgport）分别为0.44±0.31、0.08±0.21、0.37±0.25、0.30±0.22，MDA表达量（nmol/mgport）分别0.38±0.12、0.92±0.22、0.46±0.18、0.57±0.19，GSH表达量（mg/port）分别为17.80±6.12、6.11±2.82、14.71±4.18、12.28±5.011，T-SOD表达量（U/mgport）分别为3.69±2.12、1.25±0.61、3.23±0.55、2.73±0.47。与HIE-DSS组相比，DSS组结肠中ROS、MPO、MDA表达显著升高，CAT、GSH、T-SOD表达显著降低，差异有统计学意义（t=3.915，P=0.005 4）、（t=4.543，P=0.000 4）、（t=8.018，P=0.000 7）、（t=12.510，P=0.000 6）、（t=6.703，P=0.000 5）、（t=5.784，P=0.000 8）。Con组、DSS组、HIE组、HIE-DSS组的结肠组织紧密连接蛋白Muc2蛋白表达量（IOD）分别为3 019.51±23.26、2 080.25±11.18、2 690.32±17.24、2 473.50±16.04。Occludin蛋白表达量（IOD）分别为2 881.04±12.07、2 198.30±10.05、2 720.30±14.02、2 680.30±11.23，DSS组中Muc2、Occludin蛋白表达量较HIE-DSS和Con组显著降低，差异有统计学意义（t=8.743，P=0.000 7）、（t=9.634，P=0.000 9）。 结论： 高强度间歇运动作为一种新兴的运动方式，可能通过调控肠道菌群及其代谢产物，参与减轻溃疡性结肠炎的发病机制。.
Li XL, Song S, Yang Z, Tang CL, Zhang ZH, Wu ZH, Zhang XF, Jiang ZQ, Sun XW, Wang WJ
DOI: 10.3760/cma.j.cn112150-20251120-01102 | View on PubMed →
Helminth Excretory/Secretory Proteins Ameliorate Colitis Through Preservation of Intestinal Homeostasis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology | 2026-04
Inflammatory bowel disease (IBD) manifests as a sustained gastrointestinal condition driven by an ongoing dysregulated immunity, defective mucosal barrier, and microbiota dysbiosis. Parasitic helminths exert immunomodulation chiefly via excretory/secretory proteins (ESP). This study assessed the remedial effects alongside the mechanistic pathways of the ESP derived from Echinococcus multilocularis (Emu-ESP) within a dextran sulfate sodium (DSS)-provoked colitis paradigm in mice. Our results indicated that Emu-ESP treatment significantly mitigated DSS-induced colitis and notably alleviated gut microbiota dysbiosis associated with colitis. Mechanistically, Emu-ESP preserved the gut barrier by enhancing the expression of mucin and epithelial junction genes in vivo and reduced organoid injury ex vivo with decreased apoptosis and NF-κB signaling. Furthermore, Emu-ESP could promote macrophage polarization toward the M2 phenotype during colitis. In conclusion, the therapeutic effectiveness of Emu-ESP is linked to its regulation of pathways that suppress inflammation, maintain intestinal barrier function, and prevent microbiota dysbiosis, suggesting it as a promising treatment for intestinal inflammatory disorders.
Ding Y, Zhang J, Zou Y, Tang L, Liu Y, Pu L, Guo X, Li W, Wang S
Indigo Naturalis regulates the gut microbiota to increase SCFAs content and improve ulcerative colitis lesions. Frontiers in cellular and infection microbiology | 2026-03-31
The global prevalence of ulcerative colitis (UC) is approximately 5 million, and the incidence is on the rise. The gut microbiota (GM) plays a key role in the pathogenesis and progression of UC. Studies have found that Indigo Naturalis (abbreviated as Indan) and Indigo can regulate GM to improve UC, but the mechanism has not been elucidated. Using 16S rDNA to examine GM changes and evaluate the effects of Indan/Indigo treatment on short-chain fatty acids (SCFAs). The community structure of GM, there is a significant difference between the UC group and the control group. Among them, the abundance of the Proteobacteria phylum increases in the UC group, while the abundance of the Firmicutes phylum decreases. The dynamic balance between Lachnospiraceae_unclassified and Escherichia is a key factor in the pathogenesis of UC. Indan and indigo (Principal components of Indan) can alter the abundance and structure of GM. Indan and indigo increase the abundance of beneficial bacteria, leading to an increase in SCFAs content. Compared with indigo, Indan has a stronger effect on increasing the content of SCFAs. Indan can significantly increase the abundance of Clostridium_sensu_stricto_1, produce hexanoic acid. It is worth noting that the proportion regulation of Indan and indigo on the microbial structure of different phenotypes is also a new mechanism for the treatment of UC. Indan/Indigo regulates GM abundance and structure, enhances SCFAs content, inhibits inflammatory response, promotes ulcer healing, restores intestinal wall integrity, and treats UC.
Zhan XY, Xu R, Hu LZ, Zhang ZX, Zhou MS, Jia H
Biomarkers & Precision Medicine (11 papers)
Deciphering immune and cellular reprogramming during the progression from inflammatory bowel disease to colorectal cancer using multi-omics single-cell and spatial transcriptomics. Journal of translational medicine | 2026-04-18
Abstract not available.
Hosseini ST, AminianToosi K, Nemati F, BishehKolaei R, Deng Y
Longitudinal TCR repertoires in ulcerative colitis patients show features distinguishing disease states.★ Inflammatory bowel diseases | 2026-04-15
Ulcerative colitis (UC) affects an estimated 10 million people worldwide. The exact etiology of the disease is unknown, but T-cell dysregulation and aberrant activation is associated with UC-prompting research into T-cell receptor (TCR) repertoires in UC patients. However, few studies have compared UC patient TCR repertoires in flare (inflamed) and remission (uninflamed) states. Moreover, this is the first dataset to our knowledge examining multiple repertoires from UC patients over time, enabling longitudinal analyses. The T-cell receptor repertoires were obtained for 21 patients across multiple timepoints, yielding a total of 58 samples. Repertoire clonality, diversity, overlap, and gene usage frequencies were compared across all patients. Complementarity-determining region CDR3 sequences were split into K-mers (sequences of length K), and enriched K-mers in flare and remission states were identified using turboGliph. Although repertoires vary across patients, there were significant differences in the usage of 20 Vβ genes across flare and remission states. Moreover, calculation of the overlap in repertoires with enriched K-mers showed higher overlap scores than when using full TCR sequences. We identified 622 unique enriched K-mers in flare states and 495 in remission states, with only 57 overlapping between the 2 states. Overall, these results highlight the importance of analyzing Vβ gene usage and K-mer enrichment in TCR repertoires, particularly given the lack of public clones across patient cohorts. Future studies characterizing the specific antigenic targets associated with these features will pave the way for biomarker discovery in UC. This article presents an analysis of T-cell receptor repertoires from ulcerative colitis patient samples collected during colonoscopies, identifying genes and motifs associated with patients’ flare (inflamed) and remission (uninflamed) states.
Rahman S, Xu B, Farah M, Kwok A, Varghese J, Daraie A, Greenstein JL, Taylor CO, Soley N, Yan A
Editorial-Fistula Calprotectin as a Biomarker of Local Inflammation and Treatment Response in Perianal Fistulising Crohn’s Disease. Authors’ Reply.Editorial★ Alimentary pharmacology & therapeutics | 2026-04-15
A Synergistic Hydrogel-Microalgae Platform for Dual-Targeting of Intestinal and Neuroimmune Dysfunction in Inflammatory Bowel Disease.★ Advanced science (Weinheim, Baden-Wurttemberg, Germany) | 2026-04-14
Inflammatory bowel disease (IBD) is frequently complicated by comorbid depression and anxiety, creating a therapeutic vicious cycle that is currently managed with fragmented, non-integrated treatments. Here, we introduce a colon-targeted, pH-responsive hydrogel microalgal system (CV@PA-gel) designed for synergistic treatment of IBD and its psychiatric comorbidities. This engineered platform co-encapsulates the natural neuroprotective agent paeoniflorin (PA) and the gut-microbiota modulator Chlorella vulgaris (CV) within a genipin-crosslinked carboxymethyl chitosan/sodium alginate matrix. The CV@PA-gel exhibits minimal drug release in the stomach but provides sustained, targeted release in the colon, significantly enhancing the oral bioavailability and intestinal retention of its cargo. In a murine model of chronic colitis, CV@PA-gel outperforms free PA by more effectively restoring gut barrier integrity, ameliorating systemic and hippocampal inflammation, and rescuing anxiety-, depressive-like, and cognitive behaviors. Mechanistically, our findings suggest that gut-derived systemic inflammation is associated with complement C3 activation and subsequent microglia-mediated polarization of neurotoxic A1 astrocytes in the hippocampus, leading to synaptic loss. PA, delivered precisely by the hydrogel, directly suppresses this cascade by inhibiting microglial release of key A1-inducing factors. Our work establishes a versatile biomaterials strategy for disrupting the gut-brain axis pathology, offering a powerful platform for the simultaneous management of intestinal and neuropsychiatric disorders.
Lu J, Jin K, Chen B, Wang R, Hu F, Hu S, Zhong D, Li X, Zhou M
Dual-action ROS-responsive nanoparticles for synergistic suppression of pyroptosis and cfDNA in inflammatory bowel diseases.★ Journal of controlled release : official journal of the Controlled Release Society | 2026-04-13
Pyroptosis-induced production of inflammatory cytokines and elevated levels of cell-free DNA (cfDNA) are major pathogenic drivers of intestinal inflammatory diseases. Inflammatory macrophages perform a vital role in mediating inflammatory immune responses, and their targeted modulation represents a promising therapeutic strategy for colitis. Cationic nanoparticles possess considerable therapeutic promise in inflammatory disorders due to their high affinity for cfDNA. In this work, we established a combinatorial therapeutic strategy using reactive oxygen species (ROS)-responsive cationic nanoparticles that simultaneously scavenge cfDNA and transport 4-octyl itaconate (4-OI), a potent agent against pyroptosis. This dual-functional nanosystem effectively rebalances the inflammatory microenvironment by suppressing pyroptosis and neutralizing cfDNA in colonic tissues. The nanoparticles exhibited excellent biocompatibility and robust therapeutic efficacy in the context of experimental IBD in mice, with sustained drug release triggered by ROS overexpression in inflamed regions. Notably, this approach demonstrates minimal cytotoxicity and leads to substantial amelioration of disease pathology, offering an innovative therapeutic approach for the targeted control of inflammatory diseases through the coordinated targeting of multiple pathological axes.
Peng C, Han B, Qu Q, Tong A, Wang S, Li J, Wang D, Ge Y
Relationships between periodontitis and inflammatory bowel disease: Screening and functional analysis of endoplasmic reticulum stress-related biomarkers. Biochemical and biophysical research communications | 2026-04-11
This study aimed to explore the relationship between periodontitis (PD) and inflammatory bowel disease (IBD), focusing on changes in the expression of endoplasmic reticulum stress (ERS)-related genes and the screening of potential biomarkers. PD and IBD significantly affect global health, and current treatments have limitations. This study systematically screened core ERS-related genes through data mining of the Gene Expression Omnibus database, combined with differential expression gene analysis, functional enrichment analysis, and machine learning algorithms, and constructed a diagnostic model. We identified 208 differentially expressed genes shared between PD and IBD; of these, 19 were ERS-related upregulated genes, particularly XBP1 and FOS, which demonstrated good sensitivity and specificity for diagnosing PD and IBD. Functional enrichment analysis showed that these genes mainly participated in intracellular signal transduction, immune responses, and other biological pathways, suggesting that ERS plays a significant role in PD and IBD pathology. Immune infiltration analysis revealed significant differences in immune cell composition between PD and IBD, further supporting the key role of ERS in the regulation of immune responses. The identified core genes lay the foundation for improved understanding of the PD-IBD relationship and their pathological mechanisms, offering a broad prospect for future biomarker development and clinical applications.
Huang Y, Chen Z, Liang H
Glutaredoxin 1 promotes intestinal epithelial cell copper toxicity in inflammatory bowel disease. Redox biology | 2026-04-08
Protein S-glutathionylation (PSSG), a redox-sensitive post-translational modification, regulates protein conformation and activity, potentially resulting in cell death. PSSG is dynamically reversed by glutaredoxin 1 (GRX1), a critical oxidoreductase. Here, we observed elevated PSSG levels in colonic tissues of ulcerative colitis (UC) patients and experimental mouse models. Quantitative redox proteomics revealed glutathione disulfide oxidoreductase activity as the most significantly altered pathway in UC patients compared to controls. Interestingly, GRX1 undergoes site-specific S-glutathionylation at its catalytic Cys8 residue in UC patients, resulting in enzymatic inactivation. Grx1 deficiency exacerbated colonic PSSG accumulation and increased susceptibility to dextran sulfate sodium (DSS)- and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis, whereas Grx1 overexpression attenuated PSSG and ameliorated disease severity. Transcriptomic profiling identified GRX1 as a regulator of metal ion transmembrane transport, with Grx1 loss inducing copper overload and cuproptosis in vitro. Copper chelation therapy rescued colitis progression in Grx1-/- mice. Mechanistically, GRX1 associates with ATPase copper-transporting beta (ATP7B), a key regulator of cellular copper export and homeostasis, thereby stabilizing the protein by suppressing ubiquitin-mediated degradation. Therapeutic upregulation of GRX1 via pirfenidone administration mitigated DSS-induced colitis. Our findings establish GRX1 as a guardian against copper toxicity and cell death in colitis and propose GRX1 activation as a novel therapeutic strategy for UC. Directly visualizing cuproptosis in vivo would represent a critical direction for future research.
Zhang T, Zhang X, Cai H, Yu M, Liu Q, Song X, Lin B, Xu L, Li L, Shen Z
Investigation of the Effects of Postbiotics Obtained from Pediococcus acidilactici on Specific Biomarker Expressions in Intestinal Tissue. Foods (Basel, Switzerland) | 2026-04-07
The intestinal mucosal barrier is a layered structure comprising fundamental components that play important roles in regulating paracellular permeability. Disruption of intestinal barrier homeostasis predisposes to infections, mucosal damage, and metabolic and allergic diseases. To provide protection against potential damage to the intestinal mucosa, agents such as prebiotics and probiotics are recommended due to their ability to secrete components and metabolites (e.g., bacteriocins, organic acids, enzymes) that can exert beneficial biological effects. The aim of this study is to comprehensively investigate the effects of a postbiotic derived from Pediococcus acidilactici on healthy rat intestinal tissue. A total of 78 Wistar Albino rats were used in this study. Following compositional analysis of the postbiotic, the animals were administered the postbiotic orally via gavage for different durations (7, 14, 21, 28 days) and at different doses (250 mg/Kg, 500 mg/Kg, 1000 mg/Kg). Characterization of the produced postbiotic revealed a diverse spectrum of biologically active compounds, including organic acids, phenolics, and volatile compounds. Histopathological examination of intestinal sections (duodenum, jejunum, ileum, cecum, colon, and rectum) showed no pathological lesions in any of the experimental groups. Conversely, immunohistochemical analysis revealed that the postbiotic increased the expression of CLDN3, OCLN, ZO1, AQP4, and AQP8, proteins involved in intestinal permeability and fluid transport, in a dose-dependent manner. These results highlight the potential of Pediococcus acidilactici as a supportive agent in a range of intestinal pathologies, including major intestinal diseases such as Crohn’s disease, ulcerative colitis, and inflammatory bowel disease (IBD).
Demircioğlu I, Dörtbudak MB, Karaavci FA, Aydemir ME, Demircioğlu M, Genç A, Demircioğlu A, Güngör G, Di Cerbo A
The Relationship between Maresin-1 Levels and Disease Activity in Patients with Crohn’s Disease. Clinical laboratory | 2026-04
Maresin-1 is considered to be a potential regulator of inflammatory disease through its anti-inflammatory and pro-resolving properties. However, no study to date has investigated Maresin-1 levels in Crohn’s disease (CD). This study aimed to measure serum levels of Maresin-1 in patients with CD and to assess possible effects on disease activity. Thirty patients with active CD, 30 patients with CD in remission, and 30 healthy individuals were included in the study. Clinical and demographic features of patients were obtained from the hospital database. Serum Maresin-1 levels were determined by enzyme-linked immunosorbent assay. Maresin-1 level was 215.74 (118.55 - 327.46) pg/mL in the active group, 413.29 (215.82 - 726.82) pg/mL in the remission group, and 753.4 (381.5 - 901.08) pg/mL in controls (p < 0.05). An inverse correlation was found be-tween Maresin-1 and CRP in patients with active CD (p = 0.039). A Maresin-1 cutoff value of < 607.38 pg/mL showed 96.67% sensitivity and 80% specificity for the identification of CD patients in remission from controls (AUC = 0.919), while a < 327.46 pg/L cutoff yielded a sensitivity of 100% and a specificity of 100% to distinguish active CD from controls (AUC = 0.999), and finally, a < 296.28 pg/mL cutoff was also significant in identifying pa-tients with active CD from those with remission (sensitivity: 96.67%, specificity: 80%, AUC = 0.946). According to multivariable logistic regression, CD patients with decreased Maresin-1 had increased likelihood of having active disease (OR: 0.942, 95% CI = 0.892 - 0.994, p = 0.031). This was the first study to examine circulating levels of Maresin-1 in CD patients and showed that patients with active disease and those in remission had significantly lower values compared to controls. Our results suggest that Maresin-1 levels might be involved in the pathogenesis of CD. Serum Maresin-1 could be used as a diagnostic biomarker in predicting inflammation in CD and may emerge as a target for treatment.
Turan T, Gül Ö, Üreten K, Kisa Ü, Ergül B
Understanding heterogeneity in the pathogenesis and drug responses of ulcerative colitis through single-cell and spatial transcriptomics.Systematic review Frontiers in immunology | 2026-03-31
Ulcerative colitis (UC) is driven by mucosal inflammation and epithelial injury. Single cell RNA sequencing (scRNA-seq) enables high resolution profiling of immune, stromal and epithelial compartments in UC, whilst spatial transcriptomic (ST) and proteomic (SP) enable interrogation of cell-cell interactions, niche-specific expression profiles, and spatially restricted pathological processes. Although scRNA-seq, ST, and SP technologies have been rapidly evolved in the past ten years, relatively limited clinical applications have been demonstrated. This systematic review aims at comprehensively analysing current evidence in UC studies as an approach to identifying key limitations and proposing recommendations for strengthening future spatial research towards translations into clinics. A comprehensive search of Embase, Medline, and grey literature was conducted to identify studies using scRNA-seq or spatial transcriptomic or proteomic technologies in adult UC cohorts. Outcomes of interest included insights into disease pathogenesis or treatment response. scRNA-seq studies revealed alterations across the innate and adaptive immune systems, as well as stromal and epithelial compartments in UC colonic tissue. Spatial studies provided insights into: (i) cellular composition of the UC microenvironment; (ii) inflammatory features in treatment responders versus non-responders; and (iii) ligand-receptor interactions as potential spatial biomarkers and therapeutic targets. Overall, single-cell and spatial studies are deepening our understanding of UC pathogenesis and treatment response. However, they are often limited by small sample sizes and heterogeneous UC phenotypes. Future studies should prioritise robust cohort design and careful sample stratification. This will be critical to generating mechanistically precise, reproducible, and clinically meaningful insights into the heterogeneity of UC pathogenesis and treatment response. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024601628.
Phillips J, Tambakis G, Kumar R, Croft A, Brown I, Rosty C, Anderson R, Belz G, Oliver AJ, Xiong A
Clinical Value of Neutrophil Gelatinase-Associated Lipocalin as a Non-Invasive Biomarker for Intestinal Ulcer in Behçet’s Syndrome: A Pilot Study. International journal of molecular sciences | 2026-03-31
Intestinal Behçet’s syndrome (BS) is a severe phenotype associated with high morbidity and mortality. Early identification of intestinal involvement in BS remains clinically challenging due to the lack of reliable biomarkers. Neutrophil gelatinase-associated lipocalin (NGAL) is abundantly secreted during intestinal inflammation and has been recognized as a promising inflammatory biomarker. This study was designed to investigate the clinical value of NGAL for predicting intestinal involvement in BS patients. BS patients who underwent colonoscopy for suspected intestinal lesions were enrolled and classified into intestinal BS and non-intestinal BS groups. Immunohistochemistry was performed to compare colonic mucosal NGAL expression among intestinal BS, non-intestinal BS, inflammatory bowel disease (IBD) patients, and healthy controls. Serum and fecal NGAL levels were also measured in intestinal BS, non-intestinal BS, and healthy controls. Intestinal mucosal NGAL expression was significantly elevated in both intestinal BS and IBD patients, with no significant difference between the two groups. Serum and fecal NGAL levels were both higher in intestinal BS patients than in healthy controls. Notably, only fecal NGAL was significantly increased in intestinal BS compared to non-intestinal BS (p < 0.001). Multivariate logistic regression analysis identified fecal NGAL as an independent predictive factor for intestinal involvement in BS (OR = 1.093, 95% CI: 1.017-1.174, p = 0.015), with superior predictive performance over conventional inflammatory markers. In conclusion, fecal NGAL serves as a non-invasive and promising biomarker for risk stratification of intestinal involvement in BS patients. Further large-scale prospective studies are required to verify these preliminary results.
Ye JF, Zhang YX, Hu D, Cai JF, Liu YX, Zhang LY, Zou J, Guan JL
Epidemiology & Outcomes (11 papers)
The prevalence of abdominal computed tomography imaging findings in patients with inflammatory bowel disease who present to the emergency department: a systematic review and meta-analysis.★ Inflammatory bowel diseases | 2026-04-18
The diagnostic yield of abdominal computed tomographic (CT) imaging for patients with inflammatory bowel disease (IBD) in the emergency department (ED) is unclear. We aimed to estimate the prevalence of IBD and non-IBD pathologies detected by CT imaging in the ED. Multiple databases were systematically searched from inception until April 18, 2025. We included studies that reported abdominal CT findings among IBD patients in the ED. We estimated the prevalence of IBD and non-IBD findings using weighted proportions with 95% confidence intervals (CI). IBD-related findings were reported separately for Crohns disease (CD) and ulcerative colitis (UC), whereas non-IBD findings were pooled for both IBD subtypes. Overall, 19 studies were analyzed. Among patients with CD (15 studies; n = 7681 CT scans) and UC (7 studies; n = 858 CT scans), the pooled prevalence of penetrating IBD findings were low: abscesses/inflammatory masses [CD, 12% (95% CI, 10-14); UC, 3% (95% CI, 1-6)] and perforations [CD, 3% (95% CI, 2-4); UC, 1% (95% CI, 0-2)]. Rates of other IBD findings included: inflammation [CD, 43% (95% CI, 30-57); UC, 48% (95% CI, 31-65)] and obstructions [CD, 18% (95% CI, 13-23); UC, 9% (95% CI, 1-20)]. Non-IBD pathologies were uncommon: less than 5% each for pulmonary, non-IBD gastrointestinal, or genitourinary findings. In this meta-analysis, we found low rates of serious penetrating IBD complications and non-IBD pathologies detected by abdominal CT in the ED. These findings suggest that more selective use of CT imaging in the ED may be warranted.
Azward A, Ripstein G, Medawar E, Murthy S, Macdonald B, Rosenberg H, Seow CH, Singh S, McCurdy JD
Vagus nerve stimulation in Crohn’s disease: long-term outcomes, mechanistic insights, and the promise of non-invasive approaches. Bioelectronic medicine | 2026-04-17
The vagus nerve (VN) has anti-inflammatory properties. We have previously reported in a 1-year pilot study that VN stimulation (VNS) improved patients with active Crohn’s disease (CD). In this paper, we present the results of the long-term follow-up of these CD patients (between four and ten years) and raise questions about the use of VNS in inflammatory bowel disease. At the end of the pilot study, the 7 patients who ended the pilot study (corresponding to a 1-year active VNS), accepted to continue VNS as well as the 2 patients retrieved from the study, because of an early worsening (at 3 months of VNS) of their disease. Patients were then followed-up twice a year as far as possible with clinical and biological evaluation. Ileo-colonoscopy, as well as intestinal ultrasound evaluation were performed as far as possible. Vagal tone was evaluated by heart rate variability (HRV). The state perceived digestive pain score and the anxiety and depression score were also evaluated. Over a decade-long follow-up of nine CD patients implanted with VNS, sustained clinical benefits were observed despite heterogeneous disease courses and treatment histories. Three patients achieved long-term remission under VNS alone, without any additional therapy at 10 years. Several others initially controlled disease activity with VNS alone for 3–7 years before required biologics or surgery, most often during COVID-19. Clinical, biological, and endoscopic markers generally improved or stabilized, with relapse episodes responding to added standard therapies when needed. Autonomic data showed increased median parasympathetic HRV (HFnu) after implantation, persisting over six years despite interindividual variability. Median anxiety–depression scores decreased below clinical thresholds, and digestive pain shifted from moderate to low within the first year and remained low thereafter. Overall, long-term VNS was feasible, well tolerated, and associated with durable symptom control or remission in this small pilot cohort. This pilot study should primarily be viewed as a proof-of-concept demonstration that long-term invasive cervical VNS is feasible, safe, and acceptable for CD patients. It also highlights a potential therapeutic signal in a subset of individuals, supporting further investigation. The online version contains supplementary material available at 10.1186/s42234-026-00205-z.
Sinniger V, Pellissier S, Bonaz B
Increased osteoporosis burden and comparative antiresorptive effectiveness in inflammatory bowel disease: a real-world cohort study. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA | 2026-04-17
Contemporary IBD care lacks precise osteoporosis risk estimates and data on comparative therapy. In U.S., IBD patients had a 56% higher 5-year risk of a new osteoporosis diagnosis (highest in Crohn’s disease); denosumab matched bisphosphonates for 1-2-year fracture prevention in this population. Our study prioritizes early screening, steroid-sparing strategies, and individualized antiresorptive therapy. Osteoporosis is a frequent extra-intestinal complication of inflammatory bowel disease (IBD), yet its current burden and the comparative efficacy of available anti-resorptive therapies remain uncertain. Using the US TriNetX network we formed two retrospective cohorts. (1) Adults with IBD (2013-2023) were 1:1 propensity-matched to non-IBD controls to estimate 5-year risk of new osteoporosis diagnosis and identify determinants. (2) IBD patients with osteoporosis initiating denosumab or bisphosphonates (2013-2022) were matched for demographics, comorbidities, and IBD phenotype; spine/hip fractures and risk for incident onset fractures were calculated for both the cohorts. Among 143,248 patients with IBD (mean age 44.2 y; 51.8% female), risk of new osteoporosis diagnosis exceeded controls by 58% at 1 year (adjusted odds ratio [aOR] 1.58, 95% CI 1.51-1.65) and was highest in Crohn’s disease (CD) (aOR 1.79, 95% CI 1.68-1.90); ulcerative colitis (UC) also demonstrated increased 1-year risk (aOR 1.47, 95% CI 1.39-1.56). Subgroup analysis showed increased risk in patients age > 65, female sex and Asian race for UC. For CD, age > 65, female sex, nicotine dependence and alcohol use were associated with increased risk. The osteoporosis treatment cohort included 2,423 patients (520 denosumab and 1,903 bisphosphonates). After matching, denosumab produced similar 1-year (2.33% vs 3.49%, aOR 0.65 CI 0.31-1.38) and 2-year (4.65% vs 6.78%; aOR 0.67, CI: 0.39-1.14) fracture rates compared to bisphosphonates. IBD confers a substantially higher and multifactorial osteoporosis risk. Denosumab showed similar observed short-term fracture rates to bisphosphonates, although clinically meaningful differences could not be excluded. Early bone-health screening, steroid-sparing therapy, and individualized antiresorptive treatment remain essential.
Desai A, Khataniar H, Habib H, Hashash JG, Farraye FA, Regueiro M, Long M, Kochhar GS
Racial and Sex Disparities in Patients With Takotsubo Cardiomyopathy With Inflammatory Bowel Disease. Heart, lung & circulation | 2026-04-17
Takotsubo cardiomyopathy (TCM), a stress-induced cardiomyopathy, has been increasingly recognised, but its association with patients with inflammatory bowel disease (IBD) is not well established. This study aimed to assess the sex and racial differences in cardiovascular adverse events and outcomes in patients with TCM with IBD. Using the National Inpatient Sample (2016-2021), we identified adult patients (aged ≥18 years) with IBD and TCM. Demographic, clinical characteristics, and adverse inpatient outcomes were compared in patients with TCM with and without IBD. Subgroup analyses were performed to assess sex and racial disparities in outcomes among patients with TCM and IBD. Among 1,978,434 patients admitted to hospital with IBD, 3,225 (0.16%) had a concurrent diagnosis of TCM. The mean age was 64.8±13.6 years, with women comprising 83.9% of this cohort. Patients with IBD were less likely than those without IBD to have hypertension (57.6% vs 66.7%; p<0.001), diabetes (17.6% vs 24.4%; p<0.001), and hyperlipidaemia (34.1% vs 43.0%; p<0.001). IBD was linked to higher rates of venous thromboembolism (5.1% vs 3.4%; p=0.018), acute kidney injury (28.9% vs 23.8%; p=0.002), cardiogenic shock (8.8% vs 6.8%; p=0.042), extracorporeal membrane oxygenation (ECMO) use (0.6% vs 0.2%; p=0.03), and vasopressor support (6.2% vs 4.6%; p=0.048). Among patients with TCM-IBD, women were less likely to experience adverse events such as arrhythmias (odds ratio [OR] 0.51; 95% confidence interval [CI] 0.32-0.80; p=0.004). Black adults were more likely to require ECMO (OR 16.04; 95% CI 1.99-129.12; p=0.009). IBD is associated with increased adverse outcomes in patients with TCM, with notable sex and racial disparities in complications.
Agrawal A, Chopra S, Bhagat U, Banga A, Rosenzveig A, Arockiam AD, Rahman SU, Patel R, Ganatra S, Dani SS
Letter: Are All Extra-Digestive Cancer Signals in Inflammatory Bowel Disease Telling the Same Story? Authors’ Reply.Letter★ Alimentary pharmacology & therapeutics | 2026-04-16
Chronic Disease Incidence and Onset in Adults With Autism Spectrum Disorder: A 26-Year Matched Cohort Study. Journal of autism and developmental disorders | 2026-04-16
Autism spectrum disorder (ASD) is a lifelong neurodevelopmental condition, yet long‑term patterns of chronic disease in autistic adults remain poorly characterized. We examined incidence and age at diagnosis of common chronic conditions in adults with ASD compared with matched controls. We conducted a retrospective cohort study within Maccabi Health Services, including adults ≥ 18 years with documented ASD and 3:1 controls matched on age, sex, and socioeconomic status, with up to 26 years of follow‑up (1998-2024). Chronic physical and psychiatric conditions were obtained from validated registries. Time-to-event analyses were performed using Kaplan-Meier curves and Cox proportional hazards models. The cohort comprised 6,965 adults with ASD and 20,871 controls; 51% of the ASD group versus 24.5% of controls had ≥ 1 chronic condition. Adults with ASD had higher hazards and earlier diagnosis of type 2 diabetes (HR 1.47, ~ 9 years earlier), hypertension (HR 1.24, ~ 5 years earlier), overweight/obesity (HR 1.49, ~ 7.4 years earlier), inflammatory bowel disease (HR 1.60, ~ 5 years earlier), and schizophrenia (HR 2.10, ~ 4 years earlier). Overweight status amplified diabetes and hypertension risk in ASD but not controls. No significant differences were observed for COPD or cardiovascular disease. Adults with ASD experience earlier and greater chronic disease burden than matched peers, supporting earlier, tailored preventive care and systematic metabolic and psychiatric screening in this population.
Getzler I, Malachy A, Fremder A, Stolar O
Endoscopist as a key determinant of patient pain: a sigmoidoscopy screening model for unbiased assessment.Review Scandinavian journal of gastroenterology | 2026-04-14
Despite increasing standardization of training and growing attention to quality in lower gastrointestinal endoscopy, patient-reported pain during sigmoidoscopy varies considerably. This study explored whether this variability arises from differences in endoscopist performance or patient characteristics. This cross-sectional study included unsedated sigmoidoscopies performed between 2014 and 2019 within a population-based screening trial. Neither patients nor endoscopists selected each other. Pain was self-reported on a Likert scale: no pain, mild, moderate, severe. Patients were considered to have experienced pain if moderate or severe pain was reported. We used multivariable logistic regression to identify pain predictors, reporting odds ratios (ORs) and 95% confidence intervals (CI). A total of 23,483 sigmoidoscopies were performed (49.0% in men) by 47 endoscopists. Pain was reported by 607 (5.3%) men and 1612 (13.5%) women and varied substantially across endoscopists, ranging from 4.3 to 21.3%. Independent predictors of pain included young age, female sex, specific endoscopist, and presence of diverticula and inflammatory bowel disease. Greater endoscopist experience correlated with lower pain rate (OR 0.82 per additional year of experience, 95% CI 0.79-0.85). Pain was associated with lower examination completion rate (OR 0.33, 95% CI 0.29-0.37) and a trend towards a lower adenoma detection rate (ADR; OR 0.91, 95% CI 0.79-1.04). In this large study of unsedated sigmoidoscopies, the specific endoscopist strongly predicted patient-reported pain. Pain was linked to lower completion rates and ADR. Findings support ongoing quality monitoring and targeted training to minimize pain and improve outcomes. Clinicaltrials.gov Identifier: NCT01538550. Summarize the established knowledge on this subject.There is great inter-endoscopist variation in patient-reported pain during lower gastrointestinal endoscopy.Part of this variation may be attributable to case-mix differences, with more technically challenging procedures being performed by certain endoscopists.Unbiased studies are needed to clarify the endoscopist’s role in procedural pain.What are the significant and/or new findings of this study?This study provides a robust model for unbiased evaluation of procedural pain in lower GI endoscopy.Patient-reported pain varied widely and was strongly predicted by the individual endoscopist, despite immersive and standardised training, standardized endoscopy without sedoanalgesia, and no pre-endoscopy selection by patient or endoscopist preferences.Moreover, patient-reported pain was associated with lower completeness of examination and a trend toward reduced adenoma detection.The findings support systematic monitoring of quality indicators, with individualized supervision and targeted upskilling across endoscopy centres.
Schult AL, Hoff G, Randel KR, Huppertz-Hauss G, Dalén E, Matapour S, de Lange T, Botteri E
Letter: Incremental Value and Outcome Modelling in Frailty Assessment for Older Patients with Inflammatory Bowel Disease. Author’s Reply.Letter★ Alimentary pharmacology & therapeutics | 2026-04-14
Association between self-reported oral symptoms and irritable bowel syndrome: A prospective cohort study based on UK Biobank. Journal of periodontology | 2026-04-13
Although periodontal disease (PD) has been linked to an increased risk of several gastrointestinal diseases such as inflammatory bowel disease and celiac disease, research on the association between PD and irritable bowel syndrome (IBS) is still insufficiently explored, with conflicting results. We aimed to investigate the potential association between self-reported oral symptoms and IBS based on the UK Biobank cohort. Oral symptoms were assessed via questionnaire. Participants reporting at least one of gum pain, gum bleeding, or loose teeth were classified as being at high risk of PD. The primary outcome was incident IBS. Cox proportional hazards regression, incorporating multiple covariates, was applied to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) in examining the links between oral symptoms, high PD risk, and IBS incidence. Subgroup and sensitivity analyses were conducted. This longitudinal cohort study was conducted among 420,371 participants, 8642 incident cases of IBS (2.1%) were identified. Cox regression analyses showed that several oral symptoms, including mouth ulcers, gum pain, gum bleeding, toothache, and denture use, were significantly associated with an increased risk of IBS. No significant association was observed between loose teeth and IBS in any model. Compared with the low PD risk group, individuals at high risk of PD had an elevated likelihood of IBS onset (HR = 1.19, 95% CI: 1.13-1.25). Subgroup and sensitivity analyses strengthened the validity of these findings. Oral symptoms (mouth ulcers, gum pain, gum bleeding, toothache, and denture use) and high risk of PD were both associated with an increased incidence of IBS. Incorporating oral health management into comprehensive strategies may contribute to the prevention of IBS. There is a close connection between oral health and gut health. This long-term study of more than 420,000 UK adults found that individuals experiencing mouth ulcers, gum pain, gum bleeding, toothache, or denture use had a higher risk of developing irritable bowel syndrome (IBS) later in life. Additionally, participants classified as being at high risk for periodontal disease (PD; those with at least one symptom of gum pain, gum bleeding, or loose teeth) had about a 19% higher risk of developing IBS compared with the low PD risk group. Therefore, incorporating active management of oral problems into personal health practices could offer a new perspective for IBS prevention. Caring for oral health is not just about maintaining local wellness but is a crucial part of overall bodily health.
Sun Z, Li L, Zhuang Y, Hu X, Chen J, Lu S, Dai F
COVID-19 State of Emergency and Biological Therapy Persistence for Ulcerative Colitis: An Interrupted Time Series Study Using a Nationwide Claims Database. Pharmacoepidemiology and drug safety | 2026-04
To evaluate changes in biological therapy persistence for ulcerative colitis during Japan’s first COVID-19 state of emergency. Using a nationwide health insurance claims database, we identified patients with ulcerative colitis who received biological maintenance therapy between January 2014 and December 2022. Interrupted time series analysis was used to evaluate immediate level changes and post-intervention changes in trends in treatment non-persistence after the state of emergency. Kaplan-Meier analysis compared time to non-persistence between patients initiating biological therapy in the pre- and post-intervention periods using log-rank tests. Among 1197 eligible patients (67.1% male; median age, 40.0 years [interquartile range, 29.0-50.0 years]), 384 received infliximab; 375, adalimumab; 286, vedolizumab; and 152, golimumab. Interrupted time series analysis showed no clear evidence of an immediate level change in treatment non-persistence after intervention (level change, 0.38; p = 0.822) or a post-intervention change in trend (change in trend, -0.33; p = 0.167). Kaplan-Meier analysis showed no significant difference in time to non-persistence between pre- and post-intervention initiators. Biological therapy persistence for ulcerative colitis was largely maintained during the COVID-19 pandemic in Japan. These findings suggest that the pandemic was not associated with a marked change in treatment persistence in this setting. Ulcerative colitis is a chronic bowel disease that often requires long‐term treatment with biological medicines. These drugs help control inflammation and maintain remission, but their continued use can be disrupted during major public health events such as the COVID‐19 pandemic. This study aimed to assess how the pandemic influenced whether patients in Japan continued their treatment as planned. Using a nationwide health insurance database from January 2014 to December 2022, we compared treatment continuation before and after the government’s first state of emergency in April 2020. We looked at 1197 patients treated with four different biological medicines: infliximab, adalimumab, vedolizumab, and golimumab. Our analysis found no clear evidence of either immediate level changes or post‐intervention changes in trends. Overall, the persistence of biological treatment remained stable during the pandemic. These findings suggest that, in this setting, the COVID‐19 pandemic was not associated with a marked change in persistence with biological therapy for ulcerative colitis.
Mori M, Nakao YM, Honda M, Yoshida S, Kawakami K
Real-world patient characteristics, treatments, and outcomes during and after severe ulcerative colitis hospitalization.★ Journal of Crohn’s & colitis | 2026-04
Real-world data are needed to better understand the burden and outcomes of patients hospitalized with severe ulcerative colitis (UC). This retrospective cohort study analyzed US electronic health record (EHR) data with linked insurance claims to identify adults hospitalized for UC who received intravenous corticosteroids during an inpatient admission (index hospitalization) between January 1, 2014, and December 31, 2022, with ≥180 days of prior EHR activity. Results were analyzed for the overall cohort, in three subgroups: (1) no prior UC diagnosis in the EHR, (2) prior UC diagnosis without prior advanced therapy, and (3) prior UC with prior advanced therapy, and in a nested cohort of patients discharged without colectomy. Multivariable analyses assessed factors associated with colectomy before discharge. Overall, we identified 9716 patients (mean [SD] age, 46.3 [17.4] years); 83.3% had a previous diagnosis of UC and 23.8% had prior biologic use for UC. During hospitalization, 13.1% received advanced therapy; 12.2% underwent colectomy. The rate of colectomy was 12.6% in subgroup 1, 9.2% in subgroup 2, and 19.6% in subgroup 3 (P < .0001). Prior UC diagnosis with prior advanced therapy use and abnormal/missing albumin labs were associated with higher risk of colectomy. The cumulative risk of colectomy <1 year after index hospitalization was 20.4% overall and 18.5%, 16.1%, and 32.7% in subgroups 1, 2, and 3, respectively. In the nested cohort (n = 4383), one-third received advanced therapy within 90 days; 38.4% experienced a UC-related hospitalization <1 year after index hospitalization. These data from a large contemporary cohort elucidate the burden and outcomes for patients hospitalized with severe UC.
Raine T, Lewis JD, Parkes GC, Long MD, Dulai PS, Berinstein JA, Cheifetz AS, Chen Y, Huisingh C, Eccleston J
Quality of Life & PROs (11 papers)
A Prospective Study Characterizing Cognitive Function in Patients with Inflammatory Bowel Disease. Clinical and translational gastroenterology | 2026-04-17
Inflammatory bowel disease (IBD) may be associated with cognitive impairment. Cognitive decline is also linked to weaker anesthesia-induced alpha wave electroencephalographic (EEG) signals. We aimed to characterize the associations between cognition and EEG alpha power in patients with IBD. In this prospective cohort study, patients with IBD and controls undergoing diagnostic or screening colonoscopies underwent preprocedural cognitive testing using the tablet-based Brain Health Assessment (BHA), intraprocedural EEG monitoring, and follow-up testing. Primary outcomes were BHA scores and EEG alpha power. Secondary outcomes included within-participant changes in cognitive performance. We enrolled 40 patients with IBD and 42 control patients. Fifteen IBD patients and 17 controls completed follow-up cognitive testing 6-18 months after endoscopy. Patients with IBD were younger (mean age 42 vs. 56 years, p<0.001), more likely to screen positively for depression (p=0.004), and had fewer years of education (16.2 vs. 17.3 years, p=0.03). Fifteen IBD patients had active endoscopic inflammation. Adjusting for demographics, education level, and depression, EEG alpha power did not differ between groups. Median BHA scores indicated moderate likelihood of cognitive impairment in both groups. However, controls demonstrated improved within-participant follow-up performance (p<0.01), while IBD patients did not (p=0.16). IBD patients and controls demonstrate preprocedural cognitive impairment on BHA, but no differences in EEG alpha power. Lack of follow-up improvement in IBD patients may suggest lower baseline cognitive function while highlighting the importance of further investigations on cognition in this population.
Raje P, Stone TAD, Alkourabi J, Mather RV, Liu R, Higuchi M, Nipp RD, Purdon PL, Kochar B, Kunitake H
Lactate metabolism-driven lactylation: paradoxical modulation of intestinal inflammation and malignancy.Review Journal of translational medicine | 2026-04-17
Intestinal inflammation and malignancy represent two critical pathological states in the gut that severely impair patients’ quality of life. Understanding their molecular mechanisms holds significant therapeutic implications. Lactate plays a key role in cellular signaling and immune regulation. Lactylation, a modification mediated by lactate, plays a key role in epigenetic regulation. Targeting lactate metabolism and lactylation has emerged as a promising intervention strategy for intestinal diseases. This review summarizes the basic framework of the lactate metabolic system and the biological functions of lactate and lactylation, with a focus on the core mechanisms of lactylation in intestinal inflammation and malignancy. Lactylation exerts a context-dependent “paradoxical modulation” role. In intestinal inflammation, as exemplified by inflammatory bowel disease, lactylation drives macrophage phenotypic conversion, mediates gut microbiota-host interactions, regulates fibrosis progression, and modulates intestinal inflammation and tissue repair. Colorectal cancer, a major form of intestinal malignancy, is promoted by lactylation through mechanisms including immunosuppression, malignant proliferation, drug resistance, and tumor metastasis. Finally, we discuss the basis of the paradoxical modulation role of lactylation and explore the therapeutic potential of targeting lactate metabolism and lactylation as novel treatment strategies. In summary, this review highlights lactylation as a central player in intestinal diseases, providing insights into the pathomechanisms of intestinal inflammation and colorectal cancer. Lactate metabolism and lactylation hold significant potential as therapeutic targets for intestinal inflammation and malignancy, providing a promising path for precise intervention strategies in intestinal diseases.
Liu J, Liu Y, Zhang H, Li Z, Fang X, He Z, Bai Y
Letter: The Persistence of Anxiety and Depression in Inflammatory Bowel Disease-A Core Phenotype Beyond Inflammatory Activity. Authors’ Reply.Letter★ Alimentary pharmacology & therapeutics | 2026-04-17
Abstract not available.
Riggott C, Fairbrass KM, Guthrie EA, Black CJ, Selinger CP, Ford AC, Gracie DJ
Study protocol: Feasibility and acceptability of culturally adapted CBT for anxiety, depression, and stigma in Chinese IBD patients. Acta psychologica | 2026-04-16
Inflammatory bowel disease (IBD) is associated with high anxiety, depression, and stigma in Chinese populations, where Western-centric cognitive behavioral therapy (CBT) often fails to align with Confucian values of familial interdependence. This protocol for a pilot randomized controlled trial (RCT) aims to evaluate the feasibility, acceptability, and preliminary efficacy of a Confucianism-adapted CBT (CA-CBT) for Chinese IBD patients. Forty IBD patients from a single tertiary center in China via consecutive inpatient wards and outpatient clinics recruitment will be randomized to an 8-week culturally adapted CBT intervention or waitlist control. Eligibility criteria include confirmed IBD diagnosis, age ≥ 18 years, and proficiency in Chinese. The intervention incorporates Confucian principles into standard CBT modules, addressing stigma, maladaptive cognitions, and disease-related distress. Randomization will be organized by level of Confucian Coping score and type of disease using block allocation, with blinded outcome assessors. Primary outcomes will include feasibility (attendance rate ≥ 70%, retention rate ≥ 80%) and acceptability (qualitative feedback on cultural relevance, scored 1-5). Secondary outcomes will be depression (PHQ-9), anxiety (GAD-7), stigma (Social Impact Scale, SIS), and inflammatory bowel disease questionnaire (IBDQ), which will be assessed at T0 (≤7 days pre-randomization), T1 (4 weeks post-randomization ±7 days), and T2 (8 weeks post-randomization ±7 days). If found, CA-CBT is feasible and may enhance both psychological and physiological outcomes in Chinese IBD patients. Cultural integration addresses stigma and improves engagement, advocating for broader implementation in non-Western contexts. Larger trials with extended follow-up are warranted. ClinicalTrials.gov (NCT06713694).
Wang Z, Dong D, Yao L, Liu J, Zhan S, Wei M, Shao J, Luo H
Au@CeO2 nanozyme-based targeted delivery platform for computed tomography-guided synergistic antioxidant/mild photothermal therapy of inflammatory bowel disease. Journal of materials chemistry. B | 2026-04-16
The progression of inflammatory bowel disease (IBD) is exacerbated significantly by the excess production of reactive oxygen species (ROS) and pro-inflammatory cytokines In this report, a colon-targeted nanotheranostic agent, Au@CeO2 nanozymes@Eudragit S100 (termed as AuCeP@Eudragit), was prepared for computed tomography (CT)-guided synergistic antioxidant therapy and mild photothermal therapy (mPTT) of IBD by encapsulating polyacrylic acid-coated Au@CeO2 nanozymes (termed as AuCeP) into Eudragit 100. Due to its strong antioxidant and photothermal properties, AuCeP exhibits excellent ROS-scavenging activity and reduces pro-inflammatory cytokine levels, which can be further enhanced under mild 808 nm near-infrared (NIR) laser irradiation. Moreover, the contrast of intestinal CT imaging can be enhanced by the AuCeP@Eudragit introduction, because of the colon targeting of AuCeP@Eudragit as well as the strong X-ray absorption capacity. AuCeP@Eudragit shows good biocompatibility and favorable therapeutic effects in dextran sulfate sodium (DSS)-induced acute colitis, demonstrating its potential use in IBD treatment.
Liang X, Bao Y, Liu Z, Hu Z, Liu G, Li F, Wang Z
Mental Health and quality of Life in Inflammatory Bowel disease: Cross-sectional Study on its Impact. Gastroenterologia y hepatologia | 2026-04-14
Inflammatory Bowel Disease (IBD) negatively impacts patients’ quality of life. This study aims to evaluate the psychological impact and quality of life in patients with IBD. A cross-sectional study was conducted involving IBD patients treated at HUPHM. Validated questionnaires were used to assess patients’ mental health. Clinical activity was evaluated using the Harvey-Bradshaw Index and the Partial Mayo Score. Clinical data were also collected. A total of 272 patients were included. Seventy-eight percent experienced some degree of psychological impairment, and 68% reported a negative impact on their quality of life. Anxiety showed a median score of 11 (IQR: 10-13) and stress a median of 24 (IQR: 16-31), representing the most frequent psychological disturbances. Quality of life and fatigue results reflected significant impairment, with fatigue being more prevalent in women (52%, p=0.027) and associated with higher stress levels (p=0.0013) and poorer quality of life (p=0.014). Patients with Crohn’s disease exhibited worse quality of life compared to those with ulcerative colitis (median score: 46 [IQR: 34-55] vs. 49 [IQR: 41-55], p=0.04). In the occupational domain, patients with work disability showed greater psychological impairment and poorer quality of life (p=0.001). Finally, patients without prior surgery demonstrated better quality of life (p=0.032). The high prevalence of psychological comorbidities in IBD highlights the need for approaches that incorporate psychological assessment and intervention.
Arriero VG, Moya MC, de Lucas Téllez de Meneses R, Partida IG, Mateu BB, Royo VM, Castillo PB, Rodríguez MG, Mendoza MV
Association analysis of physical activity levels with mental state and quality of life in Chinese patients with inflammatory bowel disease: A multicenter study. Complementary therapies in medicine | 2026-04-12
Although the benefits of physical activity are well-recognized, the relationship between it and the psychological state and quality of life of patients with inflammatory bowel disease (IBD) in China remains unclear. Here, this study explores the association analysis between the level of physical activity in IBD and fatigue, anxiety, depression, and quality of life. In this multicentre investigative study, clinical data including age, work status, disease duration, disease stage, and bowel manifestations were collected from 321 patients with IBD. Physical activity level, fatigue, psychological status, and quality of life of IBD patients were assessed by the International Physical Activity Questionnaire (IPAQ), Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-F), Generalized Anxiety Disorder-7 items (GAD-7), Patient Health Questionnaire Depression Inventory (PHQ-9), and Inflammatory Bowel Disease Quality of Life Questionnaire (IBD-Q), respectively. Of the 321 IBD patients, 57.3% (n = 184) were diagnosed with Crohn’s disease (CD) and 42.7% (n = 137) with ulcerative colitis (UC). Among the CD patients, 42.93% had a low level of physical activity, 54.89% experienced severe fatigue, 46.20% had varying degrees of anxiety, and 50.0% had depression problems. Additionally, 21.74% reported a poor quality of life. The mean IBD-Q score was 188.09 ± 28.21. The correlation between physical activity level, psychological status, and quality of life was not statistically significant in CD patients. However, in UC patients, physical activity level was correlated with the GAD-7, IBD-Q total scores, affective functioning, and social functioning scores (P = 0.02, P = 0.023, P = 0.012, and P = 0.004, respectively), with higher levels of physical activity associated with lower GAD-7 scores and higher IBD-Q scores. Furthermore, self-fatigue and lack of time were the main reasons preventing patients from participating in physical activities. Aerobic exercise was more accepted and chosen by patients than muscle training and flexibility training. IBD has a low overall physical activity level and suffers from varying degrees of fatigue, anxiety, and depression, which affect its quality of life. Higher levels of physical activity are associated with better psychological status and quality of life. Therefore, it is essential to enhance physical activity levels among individuals with IBD.
Li Z, Wang L, Wan H, Tang Z, Wang J, Wang X, Wang W, Su J, Yin A, Zhou Q
Ethyl acetate extract of Lactococcus lactis KR-050L suppresses IL-6/STAT3 signaling in Hep3B cells and alleviates DSS-induced colitis in mice. Journal of biotechnology | 2026-04-12
Inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, is a chronic inflammatory condition characterized by persistent intestinal inflammation. Despite advances in therapeutic strategies, effective long-term management remains challenging due to side effects and limited efficacy. Therefore, there is increasing interest in alternative approaches, including probiotics and bioactive compounds derived from microorganisms. In this study, we evaluated the effects of Lactococcus lactis KR-050L ethyl acetate extract (KR-050L-EtOAc) in a murine dextran sulfate sodium (DSS)-induced colitis model. KR-050L-EtOAc administration significantly attenuated disease severity, as demonstrated by reduced body weight loss, prevention of colon shortening, and improved histopathological features in a dose-dependent manner. In addition, KR-050L-EtOAc treatment decreased pro-inflammatory cytokine levels and preserved colonic tissue integrity. These results indicate that KR-050L-EtOAc exerts anti-inflammatory and tissue-protective effects in a DSS-induced colitis model. Given that this model reflects certain aspects of intestinal inflammation, further studies are required to determine the potential relevance of KR-050L-EtOAc in human IBD.
Bak SG, Chandimali N, Bae J, Lee DS, Lee SW, Park EJ, Lim HJ, Won YS, Rho MC, Lee SJ
Marine algal TNF-α inhibitors explored by comparative docking and molecular dynamics simulations. Computational biology and chemistry | 2026-04-09
Marine ecosystems are rich in bioactive metabolites that represent a promising source of inhibitors targeting inflammatory signaling pathways. Among these, tumor necrosis factor-alpha (TNF-α) is a central pro-inflammatory cytokine driving chronic inflammation and contributing to diseases such as inflammatory bowel disease and rheumatoid arthritis. In the current study, we aim to explore potential bioactive compounds derived from marine algae-a valuable source of novel chemical entities-using integrated computational approaches, including molecular docking and molecular dynamics simulations, to identify promising inhibitors of TNF-α. More than 2000 molecules from marine algae, found in the Comprehensive Marine Natural Products Database (CMNPD) and the Natural Product Activity and Species Source (NPASS) database, were filtered based on high reactivity (score of 4 or higher) and molecular weight between 200-500 g/mol. According to our pharmacophore-based molecular docking, a shortlist of critical TNF-α residues-including Glu116, Pro117, and Tyr119-was selected as drug-target sites for the proposed inhibitors, with Tyr119 as a major target residue. Further analysis using molecular dynamics (MD) simulation indicated that bioactive marine-algae-molecules can specifically and effectively target these active residues of TNF-α. Of these compounds, CHEMBL510230 from brown algae and Floridoside from red algae showed promising inhibitory potential by interacting with these residues. Estimating binding free energies using molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) analysis confirmed that while Floridoside exhibits a stronger average binding affinity, CHEMBL510230 engages a broader network of stable residue interactions, supporting the suitability of both candidates for further preclinical investigation.
Ahmed EA, Rajendran P, Adam MSS, Abdelsalam S
Petasites japonicus Leaves Alleviate Depression in Dextran Sulfate Sodium-Induced Colitis Mice Through the BDNF/TrkB Pathway and Modulation of Inflammation. International journal of molecular sciences | 2026-04-04
Inflammatory bowel disease (IBD) is a chronic gastrointestinal disorder with a high incidence of anxiety and depression. However, the underlying mechanisms of these symptoms remain to be fully elucidated. This study investigated the effects and mechanisms of a 20% ethanolic extract of Petasites japonicus leaves (EPJ) on dextran sulfate sodium (DSS)-induced colitis and depression-like behaviors. The physiological compounds identified in the EPJ were citric acid, chlorogenic acid, caffeic acid, fukinolic acid, 3,5-dicaffeoylquinic acid, quercetin 3-O-β-D-glucose-6″-acetate, 4,5-dicaffeoylquinic acid, kaempferol-3-O-(6″-acetyl)-β-glucopyranoside, and pedunculoside. EPJ significantly alleviated DSS-induced colitis, as evidenced by improvements in body weight loss (87.41% vs. 76.02% in the DSS group), colon length (5.75 vs. 4.34 cm), intestinal permeability (52.80 vs. 163.01 μg/mL), and myeloperoxidase (MPO) activity (0.24 vs. 0.67 U/mg) (p < 0.05). Histological analysis further confirmed recovery of goblet cells and attenuation of muscle layer thickening. EPJ also reversed DSS-induced gut microbiota dysbiosis and contributed to the restoration of microbial homeostasis. Behavioral assessments showed that EPJ effectively ameliorated depression-like behaviors. EPJ improved antioxidant systems in colon and brain tissues by modulating malondialdehyde (MDA) levels and reduced glutathione (GSH) and superoxide dismutase (SOD) activity. EPJ further upregulated tight junction protein expression and suppressed TLR4/NF-κB inflammatory pathway activation in both colon and brain tissues. Moreover, EPJ modulated serum stress-related hormones, normalized hypothalamic-pituitary-adrenal (HPA) axis dysregulation, regulated the BDNF/TrkB signaling pathway, and modulated tryptophan-kynurenine metabolism. Collectively, these findings suggest that EPJ exerts protective effects against DSS-induced colitis and depression-like behaviors.
Na HR, Lee HL, Choi HJ, Heo YM, Ju YH, Kim HJ, Heo HJ
Targeting the gut-immune-brain axis: pharmacological insights from depression in inflammatory bowel disease.Review Frontiers in pharmacology | 2026-04-01
Inflammatory Bowel Disease (IBD), comprising Crohn’s Disease and Ulcerative Colitis, is a chronic inflammatory condition of the gastrointestinal tract with a remarkably high prevalence of psychiatric comorbidities, particularly Major Depressive Disorder (MDD). The traditional monoaminergic hypothesis of depression is insufficient to explain the complex etiology of MDD, paving the way for new paradigms, such as the inflammatory hypothesis of depression. This narrative review critically explores IBD as a human clinical model to investigate the connection between chronic inflammation and depression. It is argued that gut dysbiosis, a central feature of IBD, is a fundamental trigger that, through a compromised gut barrier, drives systemic inflammation and, subsequently, neuroinflammation. We detail the molecular and cellular mechanisms that link intestinal inflammation to central nervous system (CNS) dysfunction, including microglial activation, hypothalamic-pituitary-adrenal (HPA) axis dysregulation, and kynurenine pathway activation, which diverts tryptophan metabolism from serotonin synthesis to the production of neurotoxic metabolites. Robust epidemiological evidence demonstrating a bidirectional association between IBD and depression is discussed, suggesting a shared pathophysiology rather than a simple cause-and-effect relationship. Furthermore, we review the implications and emerging therapeutics, highlighting the antidepressant effects of immunobiologicals, such as anti-TNF therapies, and the potential of emerging interventions that target the microbiome, such as probiotics, psychobiotics, fecal microbiota transplantation, and anti-inflammatory diets. Furthermore, we address the limitations of the current literature, such as the lack of a quantitative definition for dysbiosis and the scarcity of clinical trials with integrated neuropsychiatric outcomes, and propose directions for future translational research. We conclude that IBD should be considered a systemic disease with significant psychiatric repercussions, advocating for an integrated therapeutic approach that combines immunomodulatory, neuromodulatory, and microbiological interventions to treat both gut and brain pathology effectively.
Simões JLB, Braga GC, Assmann CE, Bagatini MD
Pathogenesis & Basic Science (8 papers)
Oral administration of polyelectrolyte modified curcumin-loaded egg protein nanoparticles for suppression of inflammation in colitis mice.★ International journal of biological macromolecules | 2026-04-16
Ulcerative colitis (UC) is a chronic inflammatory disease affecting the large intestine, resulting in inflammation to the mucosa and submucosa of the colon. Overproduction of reactive oxygen species (ROS) plays an important role in contributing to the exacerbation of inflammation and strategies aimed at reducing ROS in the inflamed colon offer potential therapeutic benefits for managing UC. Curcumin possesses antioxidant and anti-inflammatory effects; however, it faces many challenges, such as rapid metabolism and low solubility. In this study, we developed a curcumin-loaded egg protein nanoparticle (Cur@EPN(P)) coating with a polyion complex of N,N,N trimethyl chitosan (TMC) and sodium alginate (SA). Egg protein nanoparticle significantly enhanced the solubility and antioxidant activity of curcumin, and a polyelectrolyte layer composed of TMC and SA improved the stability of nanoparticles and controlled drug release under gastrointestinal conditions. The Cur@EPN(P) exhibited an approximate diameter of 243.5 ± 7.3 nm with the pH dependent surface charge. In vitro evaluation, Cur@EPN(P) significantly increased antioxidant and anti-inflammatory properties by scavenging ABTS and hydroxyl radicals and reducing nitric oxide levels in lipopolysaccharide-activated RAW 264.7 macrophage cells. In vivo pharmacokinetic study, mice treated with orally administered Cur@EPN(P) showed a greater accumulation of curcumin in the colon tissues as compared to free curcumin treatment. The therapeutic effect of Cur@EPN(P) showed an improvement in colon length and a reduction in colonic tissue damage in colitis mice model by effectively suppressing the inflammatory and oxidative molecules. In conclusion, Cur@EPN(P) may serve as a potential orally administered nanomedicine for the anti-inflammatory management of UC.
Nguyen TV, Nguyen TT, Nguyen TT, Nguyen TH, Vong LB
Targeting PKM2-dependent glycolysis reprogrammes monocytes into Cadm1+ macrophages to promote mucosal repair and attenuate colitis progression.★ Gut | 2026-04-15
Incomplete mucosal healing contributes to progression and relapse in ulcerative colitis (UC). Currently, therapeutic strategies that promote mucosal healing and regeneration are limited and may potentiate oncogenic transformation. We aimed to identify whether modulating macrophage metabolism may facilitate mucosal healing without driving tumourigenesis. Potential therapeutic targets associated with UC disease activity and relapse were assessed in multiple omics datasets and three clinical UC studies. The function and mechanism of macrophage pyruvate kinase M2 (PKM2) in UC progression were demonstrated by macrophage-specific PKM2 knockout mice, single-cell and spatial transcriptomic profiling, and human macrophage-colonic organoid coculture models. Glycolysis was markedly upregulated in intestinal macrophages within damaged regions in UC patients, whereas PKM2 expression was associated with increased disease severity and a greater incidence of relapse. PKM2 depletion in macrophages enhanced intestinal barrier function and ameliorated colitis progression in mice. Mechanistically, PKM2 deficiency promoted monocyte differentiation into reparative Cadm1+ macrophages and enhanced Lgr5+ stem cell self-renewal via the PGE2/EP4 axis. Cross-species analysis revealed that human STAB1+ macrophages, which exhibit transcriptomic and metabolic similarities to mouse Cadm1+ macrophages, were positively associated with UC remission and spatial distribution of CD8+ T cells in colorectal cancer. Interestingly, macrophage PKM2 deletion greatly suppressed tumourigenesis in mice, accompanied by an increased abundance of Cadm1+ macrophages and enhanced CD8+ T-cell infiltration. Furthermore, targeting PKM2 in intestinal macrophages attenuated colitis progression in mice. Therapeutic targeting of PKM2-dependent glycolysis in macrophages enhanced Cadm1+ macrophage-mediated mucosal healing without driving tumourigenesis.
Zhang D, Tao P, Li J, Zhou X, Qu H, Li Y, Chen H, Yuan H, Huang J, Ji Z
Oxidative stress constrains evolution of bacteriophage host-range diversity. The ISME journal | 2026-04-14
Reactive oxygen species are essential for cellular signalling and redox homeostasis, but their accumulation causes cellular oxidative stress. In inflammatory bowel disease, oxidative stress is linked to chronic inflammation and alterations in the gut microbiota. We hypothesised that these alterations may result from the impact of reactive oxygen species on the interactions between bacteria and their viruses, bacteriophages. We followed the evolution of three Escherichia coli strains and a virulent bacteriophage in a chemostat under continuous growth and studied the impact of oxidative stress on this community. We show that both the bacteriophage and its three hosts persisted in the system over 10 days, but the relative abundance of bacteriophages was decreased in the presence of reactive oxygen species. Oxidative stress also limited bacteriophage population diversity by favouring the selection of specialist bacteriophages with a narrower host range. Concomitantly, reactive oxygen species accelerated the evolution of bacterial resistance to bacteriophages and drove the fixation of genomic mutations in genes related to cell surface structures or located in mobile genetic elements. These results highlight that oxidative stress impacts the evolutionary dynamics between bacteria and bacteriophages with consequences for microbiota diversity and potential implications in the context of intestinal inflammation.
Meynard-Doumenc C, Lamy-Besnier Q, Brot L, Messika M, Wolfromm A, Grill JP, De Sordi L
Cross-talk of gut-bone-muscle: osteosarcopenia in experimental colitis models.Review Laboratory animal research | 2026-04-14
Inflammatory bowel disease (IBD) represents a group of chronic inflammatory conditions that extend beyond the gastrointestinal tract, with profound systemic effects on the musculoskeletal system. This review comprehensively examines the experimental models that have elucidated the intricate relationship between intestinal inflammation and the development of osteosarcopenia—the concurrent deterioration of bone and muscle tissues. We analyze chemically-induced models (DSS, TNBS), genetically engineered models (T-cell transfer, IL-10 knockout, IL-2 knockout), and the Winnie mouse model of spontaneous colitis, highlighting their contributions to our understanding of IBD-associated musculoskeletal complications. The review emphasizes how these models have revealed critical molecular mediators, particularly gut-derived serotonin and vitamin D signaling pathways, that connect intestinal pathology to distant skeletal deterioration. Notably, pro-inflammatory cytokines including TNF-α, IL-6, and IL-17 emerge as central regulators affecting both bone and muscle homeostasis, explaining the synchronized pattern of deterioration observed clinically. The findings from these experimental models highlight potential therapeutic targets and intervention strategies beyond conventional approaches, including gut-derived serotonin inhibition and vitamin D modulation. This review underscores the value of chronic colitis models in elucidating the complex pathophysiology of IBD-associated osteosarcopenia and provides direction for translational research to develop integrated treatment approaches for this debilitating extraintestinal manifestation.
Sharma S
Immune dysregulation, apoptosis impairment, and enhanced seroreactivity to Anisakis simplex in Crohn’s disease: interplay of IL-7/IL-7R signalling and CD132 deficiency. Memorias do Instituto Oswaldo Cruz | 2026-04-10
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
Bromocriptine Attenuated Ulcerative Colitis and Colonic Inflammation by Inhibiting IL-1β, Likely through NF-κB Down-regulation: Integrated Network Pharmacology and in vivo Experimental Validation. Current pharmaceutical design | 2026-04-10
Gastrointestinal dopamine (DA) plays a crucial role in maintaining gut homeostasis. In patients with ulcerative colitis (UC), a decrease in DA levels due to changes in the gut microbiome can activate immune cells in the colon’s mucosal layer, leading to the secretion of various inflammatory mediators and ultimately causing damage to the colonic mucosa. In the present study, we initially analysed integrated network pharmacology and investigated the protective effect of bromocriptine (BRO), a dopamine D2 receptor (D2R) agonist, on acetic acid (AA)-induced UC in rats. Wistar rats were randomly divided into six groups (N=6/group). The intrarectal administration of AA induced UC. Treatment groups (III-IV) received three doses (2, 5, and 10 mg/kg) of BRO once daily for seven days. Group VI animals were administered mesalamine. On the eighth day, the animals were sacrificed to evaluate the lesion scores, ulcer indices, histopathological findings, nitric oxide (NO) levels, and myeloperoxidase (MPO). Finally, tissue levels of interleukin (IL-1β) and nuclear factor kappa B (NF-κB) were measured using ELISA. BRO treatment effectively improved the disease severity index (DAI), colonic lesion score, and ulcer index in rats with AA-induced UC. Histopathological studies revealed that treatment with BRO limited mucosal damage and neutrophil extravasation in colonic tissue. Moreover, biochemical assessments of MPO and NO showed a significant decrease in the levels of both inflammatory mediators following treatment with BRO. Additionally, the results indicated a reduction in the expression of IL-1β and NF-κB in colonic tissue, further supporting the amelioration of colonic inflammation caused by BRO. The present research demonstrated that BRO exerts a protective effect by influencing the expression of IL-1β and NF-κB in rats with AA-induced UC, thus restricting the activity of immune cells in the colonic mucosa. Findings of this research suggest that BRO may be a promising therapeutic agent for the management of UC.
Saha S, Mondal S, Chatterjee O, Devroy P, Sur D, Bala A
DOI: 10.2174/0113816128418229260223013818 | View on PubMed →
miR-369-3p Modulates LRRK2-Mediated Inflammation and Autophagy in RAW264.7 Macrophages. International journal of molecular sciences | 2026-04-02
Leucine-rich-repeat kinase 2 (LRRK2) is a multidomain protein highly expressed in immune cells and implicated in the regulation of immune functions including immune signaling, cytokine release and autophagy. LRRK2 is one of the therapeutic targets in Parkinson’s Disease (PD). Aberrant activation of LRRK2 can also contribute to intestinal inflammation, mainly in inflammatory bowel disease (IBD). Hence the modulation of LRRK2 may influence gut inflammation providing an improvement in disease outcomes. Over the years, microRNAs (miRNAs) have acquired much attention thanks to their potential as therapeutic targets in several pathological conditions, including inflammatory disorders. In this study, we aimed to examine the ability of miR-369-3p in the modulation of autophagy targeting LRRK2 expression. Bioinformatics analysis revealed that Lrrk2 is a target gene of miR-369-3p, and LRRK2 expression was increased in ulcerative colitis patients compared with that in a healthy control. In in vitro analysis, we validated that mimic transfection with miR-369-3p in Raw264.7 significantly reduced the expression of LRRK2 both in basal and inflammatory conditions. Moreover, the inhibition of LRRK2 limited the nuclear translocation of Nuclear factor kappa B (NF-κB) induced by lipopolysaccharide (LPS) stimulation. In turn, we found that, in inflammatory conditions, the intracellular increase in miR-369-3p precluded the inhibition of autophagy by LRRK2 by restoring autophagy marker light chain 3 (LC3)II/I ratio, BECLIN-1 and decreasing p62 expression. Furthermore, we detected that the upregulation of miR-369-3p decreased the release of pro-inflammatory mediators Tumor necrosis factor (TNF), C-C motif ligand 2/Monocyte chemoattractant protein-1 (CCL2/MCP-1), C-C motif ligand 3/Macrophage inflammatory protein-1 alpha (CCL3/MIP-1α) and C-C motif ligand 5/Regulated on activation, normal T-cell expressed and secreted (CCL5/RANTES) and increased the anti-inflammatory cytokine interleukin 10 (IL-10) in response to LPS. This study supports the anti-inflammatory potential of miR-369-3p in immune cells and suggests the potential of miR-369-3p as a therapeutic agent in the treatment of acute intestinal inflammatory conditions such as ulcerative colitis.
Scalavino V, Piccinno E, Grassi I, Armentano R, Giannelli G, Serino G
Crohn’s disease is an obstructive lymphangitis.Review★ Journal of Crohn’s & colitis | 2026-04
Crohn’s disease has been recognized by pathologists as disease of lymphatic vasculature since 1939. However, textbooks and scholarly gastroenterological associations fail to acknowledge this. Here we reference some of the published works that have made this point over the years and reference a montage of obstructed lymphatics from Crohn’s disease patients. Immunohistochemistry has allowed us to recognize that lymphatics are occluded by granulomas, the latter focally attached to endothelium. Granulomas in downstream lymphatic vasculature cause lymphocyte plugs upstream, followed by lymphangiectasia, edema, stiffening of the part and boggy mucosa. The focal necrosis at the point of granuloma attachment resembles that caused by Chlamydia suis in experimental pigs and murine norovirus in Stat1-deficient mice.
Van Kruiningen HJ, Colombel JF, Tonelli P
Pediatric IBD (6 papers)
Anti-integrin αvβ6 Immunoglobulin G antibodies are detected in pediatric colonic Crohn’s disease. Journal of pediatric gastroenterology and nutrition | 2026-04-16
Anti-integrin αvβ6 Immunoglobulin G (anti-αvβ6 IgG) has been identified as a biomarker for ulcerative colitis (UC) in adults, but they were also detected in pediatric Crohn’s disease (CD). We hypothesized that their less specificity in this population could reflect colonic inflammation rather than disease type and may be influenced by HLA-DQA105 carriage. We conducted a monocentric retrospective study using serum and clinical data from 213 pediatric inflammatory bowel disease patients and 110 controls, analyzing the association between anti-αvβ6 IgG and disease location, clinical and endoscopic activity, and HLA-DQA105 status. Anti-αvβ6 IgG were detected in 80 of 105 patients (76%) with UC, 30 of 108 patients (28%) with CD, and 2 of 110 (2%) controls. In patients with CD, anti-αvβ6 IgG positivity was significantly higher in colonic or ileocolonic phenotypes (29/84; 35%) compared to ileal or upper gastrointestinal phenotypes (1/24, 4%) (p = 0.0035). No significant association was found between antibody positivity or levels and clinical, biochemical or endoscopic activity. Anti-αvβ6 IgG was detected in 73% of patients with UC and 23% of patients with CD in endoscopic remission. The HLA-DQA1*05 allele was more frequent in antibody-positive patients (78% vs. 56%, p = 0.005), though also more common in UC than CD (82% vs. 54%, p = 0.001). In our cohort, among patients with CD, anti-αvβ6 IgG autoantibodies were predominantly detected in those with colonic localization. This observation may support previous evidence of a shared immunological background between colonic CD and UC.
Ziberna F, Grigoletto V, Leo L, Fontana G, Molinario G, Leo GD, Bramuzzo M, Lega S
Mapping the landscape and future directions of stem cell therapy for inflammatory bowel disease.Review Stem cell research & therapy | 2026-04-16
This study systematically analyzed 170 registered clinical trials to clarify the global development landscape of stem cell therapy for inflammatory bowel disease (IBD) and its core challenges, and put forward corresponding future research directions. The results showed that the research on this therapy has accelerated significantly in the past three decades, with research geographically clustered in the US, China and Spain, and severe underrepresentation of African countries. The therapy is mainly focused on Crohn’s disease (CD), especially refractory perianal fistulas, and mesenchymal stem cells (MSCs) account for over 70% of the applied cell types. Among 88 completed trials, 29.5% achieved primary endpoints, showing preliminary efficacy, yet the field faces prominent challenges: 20.6% of trials were prematurely terminated, early-phase studies dominate, Phase IV trials and long-term efficacy data are scarce, primary endpoints are highly heterogeneous, pediatric research is limited, and most completed trials have unknown outcomes. To address these issues, this study proposes that the future research should prioritize international cooperation to promote research equity, standardize efficacy endpoints, integrate long-term follow-up into study designs, optimize stem cell source and administration protocols, and implement precise patient selection. Overcoming these bottlenecks is essential to establish stem cell therapy as an effective complementary treatment for refractory IBD and improve the prognosis of patients unresponsive to conventional therapies.
Gao J, Liu Y, Xia T, He Z, Bai Y
Cross-sectional associations of clinical predictors and physical activity in pediatric inflammatory bowel disease. Pediatric research | 2026-04-15
Reduced physical activity (PA) is common in pediatric inflammatory bowel disease (IBD) and may compromise health. This study aimed to examine cross-sectional associations between PA and biomedical, treatment-related, and clinical-psychosocial factors. Single-center cross-sectional study of 45 patients (9-18 years) with Crohn’s disease or ulcerative colitis. PA was assessed using Assessment of Physical Activity Levels Questionnaire (APALQ), and health-related quality of life (HRQoL) using IMPACT-III questionnaire. Inflammatory biomarkers, treatment exposure, joint involvement, and disease characteristics were obtained from medical records. Separate multiple linear regression models were constructed for biomarker, treatment, and clinical-demographic domains and adjusted for age and sex. Lower PA levels were observed in patients with poorer HRQoL, joint involvement, and higher inflammation. In the clinical-demographic model (R² = 0.39, p = 0.009, n = 38), PA was positively associated with HRQoL (β = 0.46, p = 0.004) and negatively associated with joint involvement (β = -0.28, p = 0.041). In the biomarker model (R² = 0.23, p = 0.042, n = 37), higher fecal calprotectin was associated with lower PA (β = -0.41, p = 0.018). Treatment-related variables were not significantly associated with PA (R² = 0.18, p = 0.281, n = 29). In pediatric IBD, PA is primarily influenced by quality of life, joint involvement, and inflammatory activity rather than treatment exposure, supporting multidisciplinary strategies addressing psychosocial well-being, joint involvement and disease control. Provides novel evidence to guide multidisciplinary management strategies in pediatric IBD. Highlights the key role of psychosocial and musculoskeletal factors in shaping activity participation in pediatric IBD. Suggests that interventions to promote physical activity should target quality of life and joint involvement rather than solely biomedical parameters.
Martín-Martínez C, Saloni-Gómez N, Sánchez-Llorente P, Velasco-Rodríguez-Belvís M, Muñoz-Codoceo RA, Palomino L
Optimising multidisciplinary team care in paediatric inflammatory bowel disease: a healthcare improvement initiative from a dedicated referral centre. BMJ open quality | 2026-04-15
Paediatric inflammatory bowel disease (IBD) requires complex, multidisciplinary care. However, variation in service delivery and limited insight into patient and family experience may impact care quality. This study evaluated patient-reported experience in a specialist paediatric IBD multidisciplinary team (MDT) clinic, benchmarked findings against an internal target and informed local quality improvement.All patients and accompanying family members attending the MDT clinic at Sheffield Children’s Hospital between November 2023 and May 2024 (n=242 attendances) were invited to complete a 15-item feedback questionnaire covering access, consultation quality, communication, self-management confidence, psychosocial support and environmental factors. Responses were coded numerically (-2 to +2), summed and normalised to a percentage scale. Quality improvement methodology was applied to analyse results against a Trust-defined benchmark of 82.5% and identify SMART (Specific, Measurable, Achievable, Relevant, Time-bound) improvement targets.49 questionnaires were returned (20.2% response rate). High satisfaction was reported for consultation time and clinician responsiveness (100%), staff professionalism (94%) and clarity of management instructions (90%). Domains falling below benchmark included appointment scheduling (77.6%), waiting times (81.6%), communication with primary care (78.6%), self-management confidence (80.6%) and transition planning (66%). Based on the baseline results, we subsequently implemented SMART-based interventions, including nurse-led triage, pharmacist-led medication reviews and structured transition pathways. Early feedback suggested improved coordination and reduced waiting times.Families value MDT outpatient care in paediatric IBD, particularly in-clinic interactions and clarity of care. Persistent gaps in access, primary care coordination and transition planning highlight opportunities for targeted improvement. Integrating patient-reported experience with structured quality-improvement frameworks provides a pragmatic approach to enhancing service delivery and benchmarking outcomes.
Dipasquale V, DelNero N, Liddiard G, Hinchliffe C, Hubbard R, Londt Z, Narula P, Kapoor A
Gut Health Responses to Nutritional Interventions in Paediatric Crohn’s Disease, Including the Potential Outcomes of Mucosal Barrier Preservation: A Systematic Review.Systematic review Nutrients | 2026-04-02
Background/Objectives: Dietary treatment may play a complimentary part alongside established medical treatment pathways for children with Crohn’s disease. The aim of this review was to explore the impact of a range of dietary treatments, including the capability of preserving the mucosal barrier, during the maintenance phase of Crohn’s disease. Methods: Randomised controlled trials and cohort studies were retrieved from five databases (Cochrane library, MEDLINE, EMBASE, ScienceDirect, and Web of Science) and through hand searching (last search: June 2025). In the inclusion criteria, this review only included studies that directly assessed children with Crohn’s disease who achieved clinical remission after the induced phase but simultaneously appeared to have signs of inflammation. Results: Six studies were identified, three of which reported outcomes directly associated with the mucosal barrier, while the other studies reported intestinal inflammation and nutritional status. A range of dietary approaches were investigated, with mixed outcomes. A carbohydrate-based diet had a mixed-effect influence on the mucosal barrier, whereas an exclusion diet significantly reduced intestinal inflammation (p = 0.01). One study reported that bovine colostrum (BC) milk (a novel approach) demonstrated mucosal integrity improvement, while the timing of partial enteral nutrition (PEN) also improved nutritional status. Importantly, compliance with all these strict regimes is complex and difficult to implement, even with the support of a dietitian. Conclusions: Consideration of the most appropriate dietary approach within CD management including remission has reported mixed effects to date. Further research is needed, especially to establish the benefits and any negative consequences of dietary intervention more clearly, and especially regarding mucosal integrity.
Marind EC, McCullough F
Fungal colonization and ASCA/p-ANCA positivity in inflammatory bowel disease: a cross-sectional study from Turkey. Journal of infection in developing countries | 2026-03-31
Recent research indicates that individuals with inflammatory bowel disease (IBD) exhibit distinct intestinal fungal communities compared with healthy individuals. This study examined the relationship among anti-Saccharomyces cerevisiae antibodies (ASCA), perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA), and Candida spp. colonization to assess their utility in diagnosing IBD, differentiating subtypes, and predicting disease localization. Serum samples from 240 patients with IBD and 61 healthy controls were tested for ASCA and p-ANCA using indirect immunofluorescence assay (IIFA). Fecal samples were cultured to identify Candida species. ASCA positivity was significantly higher in Crohn’s disease (CD) (61.7%), whereas p-ANCA positivity was more frequent in ulcerative colitis (UC) (51.6%) (p = 0.005 and p = 0.002, respectively). Fluorescence intensity showed stronger ASCA reactivity in CD and higher p-ANCA intensity in UC. Candida colonization (≥ 5 CFU) was detected in 64.2% of IBD patients, with Candida albicans the most common species. Saccharomyces cerevisiae was detected exclusively in IBD patients (3.7%, p = 0.038). Higher colonization rates were observed in UC with pancolitis (78.9%) and in CD with colonic involvement (80%). ASCA intensity inversely correlated with Candida load in CD (p = 0.021), whereas p-ANCA intensity positively correlated with Candida load in UC (p = 0.038). No significant differences in Candida species diversity were observed between subtypes. These findings support the diagnostic value of ASCA and p-ANCA in distinguishing IBD subtypes and highlight their association with Candida colonization. Further studies are warranted to elucidate fungal antigen-antibody interactions and to refine subtype-specific diagnostic and therapeutic strategies.
Toraman ZA, Öner P, Erdoğan M, Afşar Karatepe B, Şahin A, Üstündağ Y, Akbulut H
Extraintestinal Manifestations (5 papers)
Shared Genetics Implicate Gut Microbiota and Immunity in Anterior Uveitis and Inflammatory Bowel Disease. Ocular immunology and inflammation | 2026-04-17
Anterior uveitis (AU) is a common extraintestinal manifestation of inflammatory bowel disease (IBD). This study investigates the shared genetic architecture and pleiotropic loci between AU and IBD. Using large-scale GWAS data from European-ancestry cohorts, we performed LD score regression to assess genetic correlations, two-sample Mendelian randomization for causal inference, and PLACO analysis to identify pleiotropic loci. Multi-trait colocalization integrating 412 gut microbiome features was conducted using HyPrColoc. Functional annotation employed FUMA and ANNOVAR, gene-based analysis used MAGMA, and drug-gene interactions were explored via DrugBank. AU showed significant genetic correlations with IBD (rg = 0.44, p = 2.0 × 10-4), ulcerative colitis (rg = 0.52, p = 6.0 × 10-4), and Crohn’s disease (rg = 0.24, p = 0.029). Mendelian randomization supported causal effects of genetically predicted IBD and its subtypes on AU risk. We identified 62 pleiotropic risk loci, including 18 with strong colocalization evidence. Functional and pathway analyses revealed enrichment of these loci in immune and inflammatory pathways, mainly the IL-17/IL-23 axis and NOD2 signaling. Multi-trait colocalization further linked a shared AU-IBD risk locus to the gut microbial MEP pathway. Several pleiotropic genes (e.g. JAK2, STAT3) represent potential drug targets. AU and IBD share pleiotropic genetic loci involved in immune regulatory pathways and gut microbiome-associated metabolic processes, revealing a potential molecular basis for their comorbidity and highlighting actionable therapeutic targets.
Li G, Wang Y, Zeng S, Li S
Differentiating IgG4-related Sclerosing Cholangitis from Primary Sclerosing Cholangitis: A Comprehensive Systematic Review and Meta-analysis of Diagnostic Features.★ The American journal of gastroenterology | 2026-04-16
Immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) and primary sclerosing cholangitis (PSC) are cholestatic disorders which may be difficult to differentiate. Importantly, PSC is an untreatable progressive fibroinflammatory disease, whereas IgG4-SC responds to immunosuppression if recognized in a timely manner. This systematic review and meta-analysis aimed to identify and define the performance of clinical, biochemical, radiographic, and histologic features to differentiate between these two diseases. A systematic search for comparative studies of IgG4-SC and PSC through November 2023 (with repeat evaluation for interval literature in December 2024) was performed and data extraction performed in duplicate. Pooled proportions, odds ratios (OR), means, and standardized mean differences of pertinent diagnostic features were calculated using random-effects inverse-variance models. We identified thirty-eight studies comparing patients with IgG4-SC and PSC. IgG4-SC patients were more likely to have pancreatic disease (p <0.001) but less likely to have inflammatory bowel disease (p<0.001) than those with PSC. Serum IgG4 was significantly higher in IgG4-SC (p<0.001), as anticipated. Radiographically, IgG4-SC demonstrated long distal strictures (p=0.02) and symmetric ductal thickening (p<0.001), whereas PSC showed a beaded appearance (p=0.038). With the exception of IgG4 staining, histologic features including periductal fibrosis were similar between these entities, though sample size was limited for these features. Our meta-analysis shows that IgG4-SC and PSC present with similar clinical and radiographic features and possibly comparable histology. A history of unusual pancreatitis and elevated IgG4 (serum or tissue) prompt assessment for more specific radiographic features which if present warrant a therapeutic treatment trial.
Wang MC, Chong AC, Grave EC, Tarakji A, Rahal K, Nastaskin L, Kunitsky A, Saric KJ, Lee H, Sahakian A
Microbial monotherapy with Leuconostoc sp. LB-P8 improves inflammation and fibrosis in mouse primary sclerosing cholangitis by inhibiting TGFβ/SMAD signaling.★ Cellular and molecular gastroenterology and hepatology | 2026-04-15
Primary sclerosing cholangitis (PSC) is a prototypical disease with an impaired gut-liver axis, frequently associated with inflammatory bowel disease, and linked to microbial dysbiosis. However, how microbes influence PSC progression remains unclear. We identified a novel Leuconostoc sp. (LB-P8) with potential anti-fibrotic properties via inhibition of TGF-β/SMAD signaling and investigated its therapeutic efficacy and mechanisms in mouse PSC models. Human intestinal cells were cultured with or without LB-P8 to assess metabolite profiles (untargeted UPLC-MS/MS) and gene expression in co-cultured myofibroblasts and macrophages (RT-qPCR). LB-P8 was orally gavaged following disease onset in three cholestatic models: bile duct ligation (BDL), 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) feeding, and the Mdr2-/- mouse. Hepatic injury, inflammation, and fibrosis were assessed by serum ALT & ALP, histology, immunofluorescence, Picrosirius red staining, and RT-qPCR. Nanostring GeoMX spatial transcriptomic analysis was performed on DDC-fed liver. LB-P8 was also tested in dextran sodium sulfate (DSS)-induced colitis. Metabolomic profiling of LB-P8 cultures revealed increased detection of 10 metabolites involved in anti-fibrosis and anti-inflammation. RNA seq analysis of hepatic stellate cells showed downregulation of TGF-β, EMT, and integrin signaling pathways. LB-P8 reduced liver fibrosis in BDL, DDC-fed, and Mdr2-/- mouse models as evident by ∼50% lower Picrosirius red staining and decreased expression of Col1a1 and Timp1. In Mdr2-/- and DDC-fed mice, LB-P8 reduced periportal macrophage number (F4/80; ∼30%). GeoMX spatial transcriptomics revealed reduced TGF-β1 in cholangiocyte and myofibroblast regions. Finally, LB-P8 suppressed expression of colonic markers of inflammation and fibrosis in the DSS model of bowel injury. LB-P8 ameliorates cholestatic liver disease progression by reducing TGF-β-mediated fibroblast activation, and periportal accumulation of macrophages. Targeting the gut-liver axis with LB-P8 may represent a novel therapeutic strategy for PSC.
Park K, Kim JY, Roh SW, Savaliya BP, Turner CA, Pirius NE, LaRusso NF, Song K, O’Hara SP
Cholangiocyte Biology in Primary Sclerosing Cholangitis and Other Cholangiopathies: Pathogenesis, Clinical Insights, and Experimental Tools.Review Physiological reviews | 2026-04-13
Cholangiocytes are specialized epithelial cells that line the intrahepatic and extrahepatic biliary tree and play a critical role in bile modification, liver homeostasis, and response to injury. Cholangiocytes exhibit notable heterogeneity and plasticity, and their dysfunction is central to a spectrum of diseases targeting the bile ducts, collectively called cholangiopathies. These disorders include genetic, infectious, immune-mediated, and malignant diseases, with Primary Sclerosing Cholangitis (PSC) representing one of the most complex and enigmatic of these disorders. PSC is a progressive, fibro-inflammatory disease of the bile ducts that is closely linked to inflammatory bowel disease, carries a heightened risk of cancer, and lacks any approved therapies. This review explores the biology of cholangiocytes, including their development, functional plasticity, and roles in secretion, absorption, and cellular signaling. We provide a detailed examination of cholangiopathies, particularly PSC, a complex cholangiopathy characterized by a paradoxical state of cholangiocyte senescence and hyperproliferation. We describe how immune cell dysfunction, the gut microbiome, genetic predispositions, and environmental factors converge to mediate PSC pathogenesis. We revisit the foundational technologies that empowered early discoveries and shaped the field as we know it today. We also explore how newer techniques such as organoid cultures, single-cell transcriptomics, epigenomics, and spatialomics have transformed our modern understanding of biliary pathophysiology. Lastly, we provide an overview of existing rodent models of cholangiopathies and discuss their relevance to human disease. PSC remains therapeutically unaddressed, and thus ongoing multidisciplinary efforts are essential to developing targeted interventions. This review serves as a comprehensive resource for researchers and clinicians navigating the rapidly evolving landscape of cholangiocyte-centered liver disease research.
Jalan-Sakrikar N, Anwar AA, Ali A, Nasser-Ghodsi N, Felzen A, Huebert RC, LaRusso NF, O’Hara SP
A Case Study and Review of the Literature on IgA Nephropathy in Crohn’s Disease. Clinical case reports | 2026-04-01
IgA nephropathy (IgAN) is the most frequently reported glomerular disease associated with inflammatory bowel disease (IBD), particularly Crohn’s disease (CD), although pediatric cases remain rare. We report IgAN in a 16-year-old male with CD following intestinal surgery and during long-term infliximab therapy, with renal impairment occurring independently of bowel disease activity. The patient presented with recurrent macroscopic hematuria, proteinuria, and acute kidney injury despite sustained intestinal remission. Renal biopsy confirmed IgAN (MEST-C: M0, E0, S1, T0, C1). Treatment with renin-angiotensin system (RAS) blockade and corticosteroids resulted in complete renal remission. Infliximab was discontinued, and a subsequent intestinal flare was successfully treated with ustekinumab. This case highlights the importance of vigilant renal monitoring in pediatric CD, particularly in patients with prior intestinal surgery or long-term biologic therapy.
Vazzana GF, Romano A, Casuscelli C, La Spada A, Santoro D, Chimenz R, Romano C
IBD-associated Neoplasia (4 papers)
Comparison of methylene blue dye-based chromoendoscopy and Fujifilm virtual chromoendoscopy (blue light imaging and linked color imaging) for dysplasia detection in inflammatory bowel disease: a prospective single-center randomized study. BMC gastroenterology | 2026-04-14
Abstract not available.
Alshatti Y, Alshammari S, Alenezi M, Alqattan A, Alshammari S, Altwala Y, Alenezi O, Ibrahim H, Alhamadi M, Alkanderi W
The Evolution of the Management of Dysplasia in Ulcerative Colitis.Review Cancers | 2026-04-04
With modern medicine and a better understanding of the ulcerative colitis disease process, there have been many changes in how we manage ulcerative colitis-related dysplasia over the past 20 years. One of the biggest concerns for these patients, given the inflammatory nature of their disease, is the progression from chronic inflammation to cancer. Patients with ulcerative colitis have about a 2.4-fold increased risk of developing colorectal cancer compared to the general population, which is concerning since colorectal cancer is the 2nd leading cause of cancer-related deaths in the United States. Traditionally, surgery was the preferred treatment for ulcerative colitis patients with dysplasia, but now, with advances in surveillance such as high-definition colonoscopy and chromoendoscopy, the management approach is more nuanced. Understanding the risk for different individuals within this patient population is key to comprehensive and personalized care management. In this review article, we will explore risk factors, surveillance methods, and classification.
Vickers AL, Fichera A
The role of extracellular vesicles in the transport and regulation of novel inflammatory mediators in IBD and its associated CRC.Review Frontiers in cell and developmental biology | 2026-03-31
Inflammatory bowel disease (IBD), comprising ulcerative colitis (UC) and Crohn’s disease (CD), is a chronic inflammation of the gut characterized by an imbalance in the intestinal microbiome and ecology. IBD raises the risk of developing colorectal cancer (CRC). CRC is one of the most commonly diagnosed cancers in the world, with high incidence rates. Extracellular vesicles (EVs) play a crucial role in intercellular communication and are vital for maintaining intestinal homeostasis. Recent research highlights novel inflammatory mediators, such as specialized pro-resolving mediators (SPMs), damage-associated molecular patterns (DAMPs), alarmins, non-coding RNAs (ncRNAs), and metabolic intermediates, as crucial in the pathophysiology of IBD and CRC. These novel inflammatory mediators are transported by EVs, influencing the pathogenesis of IBD and associated CRC. Therefore, this article examines the role of novel inflammatory mediators transported by EVs in the pathogenesis of IBD and related CRC, as well as the interaction between EVs and the tumor microenvironment. We also review new research on EV use as a diagnostic indicator and on the potential of EVs, such as mesenchymal stem cell-derived EVs (MSC-EVs), as therapeutic delivery channels for cancer treatment targeting unique inflammatory mediators.
Zhang C, Tang X, Chen S, Akanyibah FA, Mao F
Enterococcus-driven metabolite-host gene networks in IBD-associated colorectal carcinogenesis: integrative multi-omics and experimental validation. Frontiers in cell and developmental biology | 2026-03-30
This study aims to elucidate the role of Enterococcusin the progression from inflammatory bowel disease to colorectal cancer (CRC), with a focus on identifying key metabolites and host genes regulated by Enterococcusand their influence on CRC development. Using the database gutMGene, gutMDisorder and MACdb, we mined the key metabolites and human genes. We acquired the activated genes (panel 1) and inhibited genes (panel 2), and metabolite associated genes (MAGs, panel 3). Subsequent analyses included protein-protein interaction (PPI) network construction, functional enrichment, differential expression and survival analysis in CRC, and immune infiltration assessment. In vitro experiments validated the regulatory effects of E. faecalisand its key metabolites on candidate genes. Single-cell RNA sequencing (scRNA-seq) was used to dissect cell-type-specific expression patterns within the tumor microenvironment. We screened 12 activated genes (Panel1: IL11, IL24, IFNG, IL10, IL12B, IL1B, IL6, TNF, ANGPTL4, CXCL10, PLIN2, and PPARG) and four inhibited genes (Panel 2: CXCL8, IL6, TNF, and PDCD6IP). Three metabolites were found important in CRC development: agmatine, formate, and levodopa, linking with 28 MAGs. In particular, IL10, IL11, CXCL10, IL1B, and IFNG are protective genes in CRC; and there are four MAGs associated with CRC PFS, and they are all survival-risk genes: COMT, PRL, EDNRA, and MAPK3. Experimental validation showed that E. faecalis significantly upregulated the level of IL-10 and IL-1B in CRC, while its metabolites agmatine and levodopa markedly induced the expression of the survival-risk gene MAPK3. scRNA-seq revealed cell-type-specific expression patterns, where IL1B was significantly upregulated in both tumor epithelial and myeloid cells, and IL10 was specifically elevated in tumor epithelial cells. In contrast, MAPK3 exhibited divergent trends, showing downregulation in tumor epithelial cells but significant upregulation in myeloid cells. Enterococcus exhibits a dual role in colitis-associated CRC, correlating with both tumor-suppressing and tumor-promoting effects. It may activate protective immune genes while its metabolites, agmatine and levodopa, alter the expression of oncogenic MAGs. The findings highlight the complex metabolite-host gene networks driven by Enterococcusand suggest estradiol and sodium arsenite as potential adjuvant therapies, offering new insights into precision intervention for CRC.
Huang G, Liu J, Cheng Z, Chen Y, Chen K, Liu W, Liu H, Xia X, Lu M, Cui W
Intestinal Ultrasound (IUS) (4 papers)
Letter: Beyond the Mucosa-Strengthening the Case for Transmural Healing as a Monitoring Target in Crohn’s Disease.Letter★ Alimentary pharmacology & therapeutics | 2026-04-17
Use of Intestinal Ultrasound in a Tight monitoring approach in Crohn’s disease: a multicentre prospective study.★ Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association | 2026-04-15
Intestinal ultrasound (IUS) is increasingly used to monitor Crohn’s disease (CD) activity, yet its optimal role in tight monitoring strategies remains unclear. We aimed to assess the predictive role of ultrasonographic parameters in determining endoscopic remission (ER) after one year of anti-TNFα, and the correlation of IUS parameters with other outcomes longitudinally. Multicentric prospective longitudinal study enrolling adult patients with active CD starting anti-TNFα. Biomarkers and IUS were performed at baseline, week (W)14, W30 and W54; ileocolonoscopy and magnetic resonance enterography (MRE) were performed at baseline and W54. The primary outcome was the predictive value of IUS remission (normalization of bowel wall thickness (BWT), stratification, vascularization and mesenteric fat) for ER at W54 (segmental SES-CD=0). The International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) optimal cut-point to detect ER was identified using ROC analysis. Sixty-three patients were included, of whom 57 were followed until W54. After one year of therapy, 40%, 42% and 33% achieved endoscopic, IUS and MRE remission, respectively. Patients with ER had a significantly lower median BWT and IBUS-SAS score at all timepoints. The best predictors for ER were IBUS-SAS <56.6 (AUC 0.861) and BWT <2.9mm (AUC 0.802) at W14. On multivariable analysis, IBUS-SAS<56.6 at W14 was the only independent predictor for ER (OR 19.0; 95%CI 1.91-189.6; p=0.012). Early IUS evaluation can non-invasively predict treatment outcomes, supporting its integration into tight monitoring protocols for CD. IUS offers a real-time, cost-effective alternative to endoscopy and imaging, potentially enabling timely therapy optimization to improve patient management.
Palmela C, Revés J, Frias-Gomes C, Morão B, Neto C, Bargas A, Glória L, Cravo M, Manso M, Dias de Castro F
High-end intestinal ultrasound versus mid-end systems benchmarked against tandem ileocolonoscopy in inflammatory bowel disease (HUMID): a paired prospective, validating confirmatory study.★ EClinicalMedicine | 2026-04-01
Intestinal ultrasound (IUS) is redefining inflammatory bowel disease (IBD) monitoring, but global adoption remains limited by the cost of high-end systems. This study evaluated whether widely available mid-range equipment provides comparable diagnostic accuracy without additional cost. We conducted a prospective, cross-sectional, paired diagnostic accuracy study at a single IBD centre in India from September 2024 to October 2025. We included patients aged 18-75 years with confirmed ulcerative colitis (UC) or Crohn’s disease (CD). Trained operators performed same-day blinded assessments using a mid-end (Siemens ACUSON S2000) and a high-end system (Samsung RS80 EVO). Blinded ileocolonoscopy with central review served as the reference. Endoscopic remission was defined as Ulcerative Colitis Endoscopic Index of Severity (UCEIS) ≤ 1 for UC and Simple Endoscopic Score for Crohn’s Disease (SES-CD) ≤ 2 for CD. Sonographic activity was assessed using the Milan Ultrasound Criteria (MUC) for UC and the International Bowel Ultrasound Simplified Activity Score (IBUS-SAS) for CD. Diagnostic accuracy, segment-wise performance, and reclassification impact were evaluated. Paired comparisons used McNemar testing for proportions, receiver operating characteristic (ROC) analysis with area-under-the-curve (AUC) comparison, and agreement analyses using Bland-Altman and concordance methods. This study is registered with ClinicalTrials.gov, NCT06938295. 450 patients underwent paired IUS and ileocolonoscopy (239 UC, 211 CD; median age 36 years; 32% female). In UC, sensitivity was 94.2% with the mid-end and 97.1% with the high-end system (Δ +2.9%; 95% CI -3.8 to 9.6), with identical specificity (54.5%). In CD, sensitivity was 85.1% versus 87.6% (Δ +2.5%; 95% CI -8.2 to 13.0) and specificity 62.0% versus 60.0% (95% CI -28.0 to 24.2); accuracies differed by <3%. Segment-wise performance showed no significant differences across any bowel regions. ROC analyses showed good-excellent discrimination [AUC: 0.75-0.93 (UC); 0.83-0.94 (CD) in various segments], with overlapping curves and strong score correlation. Reclassification analysis showed a net gain of +6 patients (diagnostic odds ratio 1.8, 95% CI: 0.9-3.5) for high end machine. Bland-Altman and concordance analyses demonstrated minimal bias and high agreement. Decision-curve analysis confirmed equivalent net clinical benefit. High-end IUS conferred no measurable diagnostic or clinical advantage over mid-range equipment when examinations were performed by trained operators using standardised scoring systems, supporting mid-range systems as scalable and cost-effective tools for IBD monitoring. No external funding.
Pal P, Mateen MA, Naaz SM, Pooja K, Nittala R, Singh A, Reddy BK, Reddy Vasepally PK, Najbuddin SM, Maharshi TS
The predictive value of intestinal ultrasound for treatment response in inflammatory bowel disease: a systematic review and pooled data analysis.Systematic review★ Journal of Crohn’s & colitis | 2026-04
Intestinal ultrasound (IUS) is a promising tool for predicting treatment response in inflammatory bowel disease (IBD). We aimed to systematically review existing literature on the predictive value of IUS for treatment response. A literature search was performed until May 2025. We included articles assessing treatment response in IBD using IUS. Data were analyzed separately for Crohn’s Disease (CD), ulcerative colitis (UC) and acute severe ulcerative colitis (ASUC). Pooled data analysis was performed for bowel wall thickness (BWT) in CD patients starting anti-TNF (tumor necrosis factor). In total, 31 articles were included (18 CD, 9 UC, and 4 ASUC). In 8/10 CD studies, IUS at week 4-8 could distinguish future responders, with BWT change ranging from -43% to -14.6% in responders vs. -14% to + 2% in nonresponders. In the pooled data analysis of anti-TNF-treated CD patients (n = 236) a 23% decrease from baseline at week 4-8 (area under the receiver operating characteristic curve [AUROC] 0.82) and 27% decrease at week 12-16 (AUROC 0.78) could predict future response. In 2/2 UC studies, IUS after 4-8 weeks could predict future endoscopic remission vs. non-remission with a decrease in BWT ranging from -55% to -49% vs. -38% to -17% respectively. In ASUC, change in BWT after 1-3 days could predict need for salvage therapy (-34% vs. -10%). Intestinal ultrasound predicts response at an early stage after treatment initiation, both in CD as well as in UC. In anti-TNF-treated CD patients, 23% and 27% decrease in BWT after 4-8 weeks and 12-16 weeks of treatment initiation predicts outcomes.
Vos JMBW, Teichert C, De Voogd FAE, Pruijt MJ, Jamaludin FS, D’Haens GRAM, Benninga MA, Koot BGP, Gecse KB
Pregnancy & Reproductive Health (4 papers)
Clinical utility of blood-based biomarkers in pregnant women with inflammatory bowel disease. Expert review of molecular diagnostics | 2026-04-16
Pregnancy in women with inflammatory bowel disease (IBD) is common, and active disease remains a key driver of adverse maternal and fetal outcomes. Maintaining remission throughout pregnancy is therefore essential, however clinicians lack reliable, minimally invasive tools to monitor disease activity and stratify pregnancy-related risk. This expert review critically addresses the current evidence on blood-based biomarkers for pregnancy in women with IBD. We discuss the impact of maternal disease activity on pregnancy outcomes, the bidirectional relationship between pregnancy and IBD disease course, and the potential contribution of placental dysfunction and oxidative stress to adverse outcomes. Established and emerging biomarkers, including fecal calprotectin, inflammatory, angiogenesis-, and oxidative stress-related biomarkers, are evaluated. We further outline methodological challenges, limitations of single biomarkers, and unmet needs in validation and clinical translation. We emphasize that the persistent focus on isolated biomarkers is unlikely to meet the complexity of pregnancy in patients with IBD. Instead, we propose that integrative multi-omics approaches capturing interacting biological processes represent a more conceptually sensible path forward. While rigorous prospective validation and standardization are essential before clinical implementation, such strategies hold promise for more personalized risk stratification and monitoring of pregnant patients with IBD.
Holstein HJ, Bouwknegt DG, Gordijn SJ, Dijkstra G, Cantineau AEP, Mian P, van Goor H, Visschedijk MC, Bourgonje AR
Quality of healthcare delivery in inflammatory bowel disease pregnancy: a scoping review.★ Inflammatory bowel diseases | 2026-04-15
Inflammatory bowel disease (IBD) is associated with an increased risk of adverse pregnancy outcomes. The number of individuals affected by IBD during their reproductive years is expected to increase in parallel with rising disease prevalence. Increasing disease burden and costs of care threaten access to quality health care delivery. Quality of healthcare describes how healthcare delivery services achieve desired evidence-based patient-reported and clinical outcomes. Given that IBD has implications for patients during pregnancy, a dedicated exploration of how quality of care may be optimized for this patient group is warranted. In this scoping review, we apply a framework assessing structural, process, and outcome indicators to examine the current quality of healthcare in IBD pregnancy, identify and discuss barriers to achieving quality care, and systematically appraise the existing models used to provide care for IBD patients during their pregnancies. This review explores quality of healthcare delivery for patients with IBD during pregnancy by assessing structural, process, and outcome indicators. We discuss barriers to achieving quality care, appraise existing models, and identify future targets for optimization of care delivery in this population.
Chin S, Demase K, Corte C, Wong D, Prentice R, De Cruz P
Gasdermin D-Mediated Release of IL-33 Results in Fetal Brain Developmental Abnormalities During Maternal Colitis.★ Advanced science (Weinheim, Baden-Wurttemberg, Germany) | 2026-04-13
Maternal inflammatory bowel disease (IBD) is associated with an increased incidence of autism spectrum disorder in offspring. The mechanism behind this phenomenon remains largely unknown. Here, we found that offspring from colitic dams exhibit increased brain weight. These offspring also show excessive neural stem cell (NSC) proliferation and behavioral deficits. Furthermore, Gsdmd cleavage is elevated in the colonic epithelium of colitic dams. This increase is associated with developmental abnormalities in the fetal brain. Mechanistically, excessive NSC proliferation is driven by increased IL-33 release from the maternal colonic epithelium in a Gsdmd-dependent manner. In contrast, we found no evidence that maternal luminal LPS leakage or increased fetal microglia accounts for this phenotype. Our study demonstrates that excessive pyroptosis in the maternal colonic epithelium leads to neurodevelopmental defects and disrupts neuroimmune homeostasis in the offspring.
Jia H, Zhang S, Ma K, Zhou J, Jiao J
Disseminated amoebiasis in pregnancy: A maternal near-miss. Obstetric medicine | 2026-04-10
Disseminated amoebiasis in pregnancy, though rare, can be life-threatening and mimic bacterial sepsis or inflammatory bowel disease (IBD). We report a case of maternal near-miss at 18 weeks of gestation due to amoebic colitis and liver abscess. The woman presented with fever, bloody diarrhoea, and abdominal pain, initially suspected to be bacterial sepsis, and treated with ceftriaxone. Ultrasound revealed hepatic abscesses and caecal thickening. Following massive rectal bleeding and hypovolemic shock, colonoscopy confirmed Entamoeba histolytica infection. Liver abscess drainage yielded anchovy-sauce pus, and stool, blood, and aspirate cultures were negative. Metronidazole therapy led to clinical improvement. This case highlights the importance of considering disseminated amoebiasis in pregnant women with haemorrhagic diarrhoea and sepsis. Early histopathological confirmation and targeted anti-amoebic therapy are essential for effective management, preventing severe complications such as haemorrhagic shock and liver abscess.
Gupta A, Choudhury S, Pathak P, Singla D, Phulwani AK, Sharma T
AI & Machine Learning (3 papers)
Inflammatory bowel disease burden in China and the United States from 1990-2023 and prediction to 2050. Internal and emergency medicine | 2026-04-16
Inflammatory bowel disease (IBD) shows divergent epidemiological trends in China and the United States, necessitating country-specific forecasting approaches. This study compares IBD burden between both countries from 1990 to 2023 and projects future trends to 2050 using a multi-algorithm forecasting framework. We analyzed data from the Global Burden of Disease Study 2023 (GBD 2023) for IBD incidence, prevalence, mortality, and disability-adjusted life years (DALYs). Joinpoint regression was used to characterize temporal trends, and the intrinsic estimator method was applied for age-period-cohort (APC) analysis. Future projections employed ten forecasting algorithms spanning traditional time series models, machine learning, and deep learning architectures, with optimal model selection for each country-measure combination based on cross-validation mean absolute percentage error (MAPE). Between 1990 and 2023, China experienced a rise in age-standardized incidence from 0.75 to 1.41 per 100,000 (average annual percentage change [AAPC] = 1.93%) alongside declining mortality (AAPC = - 2.55%). In contrast, the United States maintained relatively stable incidence (AAPC = 0.32%) but saw increasing death rates (AAPC = 1.71%). APC analysis revealed declining cohort effects in both countries, with steeper declines observed in China. The optimal forecasting model varied by country and measure: ElasticNet was most frequently selected for age-standardized rate projections, while Prophet and Holt’s damped trend models performed best for absolute case number projections. By 2050, China’s age-standardized incidence and prevalence rates are projected to increase (1.69 and 11.50 per 100,000, respectively), while death and DALY rates are projected to decline (0.22 and 4.12 per 100,000). For the United States, age-standardized rates are projected to remain relatively stable or decline modestly, while absolute case numbers are projected to increase substantially (prevalent cases: 1,208,253; deaths: 10,328), driven by population growth and aging. China’s IBD burden is characterized by rising incidence and prevalence alongside declining mortality, while the United States faces increasing absolute disease burden driven primarily by demographic change. The multi-algorithm forecasting approach, with country- and measure-specific model selection, accommodates the heterogeneous epidemiological patterns observed between these two countries.
Cheng B, Yan J, Huang Y, Fang J, Zhou X, Chen X
Identification and Validation of Transcriptomic Signatures in Inflammatory Bowel Disease with Metabolic Syndrome via Bioinformatics and Machine Learning. Genetic testing and molecular biomarkers | 2026-04-14
Inflammatory bowel disease (IBD) is a chronic, nonspecific inflammatory disorder affecting the gastrointestinal tract. The condition’s pathology not only involves the digestive system but also can impact various organs and tissues throughout the body. Metabolic syndrome is a clinical syndrome characterized by obesity, insulin resistance, hypertension, and hyperlipidemia. Extensive research suggests a potential association between IBD and metabolic syndrome. To seek biomarkers related to the diagnosis and treatment of IBD and metabolic syndrome. In this study, we utilized bioinformatics, integrated transcriptome analysis, and machine learning to develop a diagnostic model for the co-occurrence of IBD and metabolic syndrome. We applied two machine learning algorithms to select relevant features Least Absolute Shrinkage and Selection Operator and Random Forest (RF). Moreover, through external datasets and quantitative real-time polymerase chain reaction (qRT-PCR) experiments, we validated our findings. We identified nine candidate gene-expression-based biomarkers (CCR6, CST7, LIMK2, TCF4, THBS3, CARS2, IFI27, LETM1, LOXL1) associated with immune and metabolic regulation that exhibited discriminatory potential for IBD complicated by metabolic syndrome. Furthermore, a column chart for diagnosing IBD in metabolic syndrome patients is provided. Our study demonstrates that integrated bioinformatics and machine learning approaches can identify transcriptomic signatures associated with IBD and metabolic syndrome, providing candidate biomarkers for further validation.
Yin YZ, Yan CS, Wu L, Li GQ, Pei XY, Xue YZ, Ren YL, Sun HW, Sheng YY
The food additive 4-hexylresorcinol impairs intestinal stem cell function and exacerbates inflammatory bowel disease in Drosophila melanogaster via suppression of mapk signaling pathway. Cellular and molecular life sciences : CMLS | 2026-04-14
Abstract not available.
Fan X, Yan J, Yuan Y, Chen Y, Chen H
Nutrition & Lifestyle (3 papers)
Dietary total antioxidant capacity alleviates inflammatory bowel disease-related surgery, gastrointestinal cancer, and mortality risks among middle-aged and older individuals. The journal of nutrition, health & aging | 2026-04-17
This study aimed to investigate the association between dietary total antioxidant capacity (TAC) and the risks of clinical outcomes, including surgery, gastrointestinal cancer, and mortality, among middle-aged and older individuals with IBD. Nationwide prospective cohort study. We included middle-aged and older participants with IBD when recruited in the UK Biobank. Dietary TAC was calculated by the oxygen radical absorbance capacity from the food by repeated dietary recalls. The outcomes representing IBD prognosis include IBD-related surgery, gastrointestinal cancer, and death events. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazard models. Polymorphism of antioxidant-related enzymes genes was ascertained via genotype data. With a median follow-up period of 10.9 years, we documented 174 cases of IBD-related surgery, 52 gastrointestinal cancer, and 189 death events among 2487 IBD participants. Compared to the lowest quartile of dietary TAC, participants in the highest quartile presented lower risks of IBD-related surgery (HR 0.53; 95% CI 0.34-0.84; P-trend = 0.005) and all-cause mortality (HR 0.61; 95% CI 0.39-0.96; P-trend = 0.014). Compared to the lowest decile, participants in the higher deciles of dietary TAC had a lower risk of gastrointestinal cancer (HR 0.39; 95% CI 0.19-0.83; P = 0.014). We also found genetic variants in catalase gene CAT and antioxidant transporter gene SLC2A14 modified the association between dietary TAC and IBD prognosis. Higher dietary TAC was associated with better prognosis of middle-aged and older individuals with IBD, including lower risk of related surgery, gastrointestinal cancer, and all-cause mortality, suggesting the importance of adherence to high-TAC diet in IBD management.
Fu T, Dan L, Wang S, Wu X, Sun J, Yuan S, Wolk A, Ludvigsson JF, Wang X, Larsson SC
[Advances in clinical management of acute severe ulcerative colitis]. Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences | 2026-04-09
Acute severe ulcerative colitis (ASUC) is a critical emergency in inflam-matory bowel disease. Some patients do not respond to first-line intravenous corticosteroid therapy and require timely salvage treatment. Previously, guidelines recommended infliximab and cyclosporine as the main salvage therapies; however, recent years have witnessed clinical advances. Accelerated and intensified dosing regimens of infliximab, compared with standard dosing, may help patients with high inflammatory burden and hypoalbuminemia achieve earlier clinical and biochemical remission. Among small-molecule Janus kinase inhibitors, tofacitinib as an adjunct to intravenous corticosteroids improves short-term response rates, while upadacitinib shows promise as a salvage therapy when intravenous corticosteroids, conventional or intensified infliximab are ineffective. For patients unresponsive to monotherapy or those with extraintestinal manifestations, dual targeted therapy, through multi-pathway synergistic blockade, achieves superior clinical, endoscopic, and biochemical outcomes compared with monotherapy, providing new evidence-based support for treatment optimization. In addition, exclusive enteral nutrition and hyperbaric oxygen therapy play important roles in the comprehensive management of ASUC by modulating gut microbiota and promoting mucosal healing, respectively. This article reviews the therapeutic outcomes and limitations of these emerging pharmacological agents or regimens in the clinical treatment of ASUC, aiming to provide a reference for optimizing clinical management strategies for ASUC. 急性重症溃疡性结肠炎（ASUC）是炎症性肠病中的危急重症之一，部分患者对一线静脉激素治疗无应答，须及时启动挽救治疗。以往指南推荐的挽救治疗药物主要包括英夫利西单抗（IFX）和环孢素，近年来有临床治疗新进展。IFX加速和强化给药方案相比标准给药方案可能有助于高炎症负荷及低白蛋白血症患者更早实现临床和生化缓解。小分子Janus激酶抑制剂中托法替尼辅助静脉激素可提高短期应答率，乌帕替尼在静脉激素、传统或强化剂量IFX疗效不佳时展现出良好的挽救治疗价值。对于单药治疗无效或合并肠外表现者，双重靶向治疗通过多通路协同阻断，在临床应答、内镜及生化指标的改善情况均优于单药治疗，为治疗优化提供了新的循证依据。此外，全肠内营养和高压氧治疗分别通过调节肠道菌群和促进黏膜愈合，在ASUC的综合管理中发挥了重要作用。本文回顾并综述了上述治疗药物或方案在ASUC临床治疗中的应用成果及局限性，旨在为优化ASUC临床治疗策略提供参考。.
Shao W, Zhou Y, Xu F
Risk of avoidant/restrictive food intake disorders in patients with inflammatory bowel disease: a matched cross-sectional case-control study.★ Journal of Crohn’s & colitis | 2026-04
Individuals with inflammatory bowel disease (IBD) often modify their diet to manage symptoms; however, these behaviors may evolve into eating disorders, including avoidant/restrictive food intake disorder (ARFID). We assessed the risk of eating disorders and ARFID in patients with IBD compared with healthy controls (HC), explored differences by age at diagnosis, and examined associations with malnutrition and disability. In this cross-sectional study, adult patients with confirmed IBD, stratified by pediatric- vs adult-onset, were matched with HC. ARFID risk was assessed using the Nine-Item ARFID Screen (NIAS-9) and eating disorders risk with the Eating Attitudes Test-26 (EAT-26). Nutritional status was evaluated with the Patient-Generated Subjective Global Assessment (PG-SGA) and disability with the IBD-Disk and modified IBD-Disk. A total of 706 participants completed questionnaires (355 IBD, 351 HC). Eating disorder risk did not differ between groups (11.3% vs 10.8%, P = .91). ARFID risk was higher in IBD (13.5% vs 5.7%, P < .001), with more fear-driven eating (P < .001) and lower picky eating (P < .001) and appetite scores (P = .033). ARFID risk did not differ by age at onset (P = .39). Independent associated factors included active disease (odds ratio [OR] 2.34, 95% confidence interval [CI] 1.10-5.01), malnutrition (OR 2.31, 95% CI 1.04-5.13), dietary changes (OR 4.32, 95% CI 1.92-9.74), and eating disorder risk (OR 7.47, 95% CI 2.95-18.90). Even in remission, ARFID risk remained elevated compared to HC (10.1% vs 5.7%, P = .03). ARFID risk in IBD is nearly twice that of HC and strongly associated with disease activity, malnutrition, and disability, supporting the importance of ARFID screening in routine IBD care.
Nardone OM, D’Amico F, Calabrese G, Parigi TL, Gargiulo AM, Bencardino S, Palumbo F, Petolicchio M, Guarino AD, Rispo A
Drug Safety & Pharmacovigilance (2 papers)
Refractory ulcerative colitis patient keeping complete remission with drug-free after hematopoietic stem cell transplantation for ileocecal diffuse large B-cell lymphoma. Clinical journal of gastroenterology | 2026-04-19
Abstract not available.
Kawaguchi E, Minami N, Nishida K, Fujii M, Umeda M, Watanabe M, Matsumura T
Impaired Macrophage Efferocytosis: Shared Mechanisms and Therapeutic Implications in Immune-Mediated Inflammatory Diseases.Review Journal of inflammation research | 2026-04-08
Efferocytosis, the specialized phagocytic clearance of apoptotic cells, is a fundamental mechanism for maintaining tissue homeostasis and immune tolerance. Among professional phagocytes, macrophages play a central role due to their high plasticity and tissue-resident properties. By recognizing and engulfing apoptotic cells through a repertoire of receptors and bridging molecules, macrophages prevent secondary necrosis and inflammation and actively shape the local immune microenvironment via metabolic and epigenetic reprogramming. Defective efferocytosis has been increasingly implicated in the pathogenesis of immune-mediated inflammatory diseases (IMIDs), including systemic lupus erythematosus, rheumatoid arthritis, Sjögren’s syndrome, inflammatory bowel disease, psoriasis, atopic dermatitis, and autoimmune liver diseases. Impairments in efferocytosis trigger persistent inflammation, autoantigen exposure, and tissue damage, thereby fueling chronic disease progression. Recent mechanistic studies highlight the dysregulation of TAM receptors, bridging molecules, and intracellular signaling pathways as critical determinants of efferocytosis dysfunction in IMIDs. In this review, we propose defective macrophage efferocytosis as a shared pathogenic mechanism across diverse IMIDs and integrate emerging evidence linking efferocytosis to immunometabolic and epigenetic rewiring in chronic inflammation. We further discuss therapeutic strategies targeting efferocytosis pathways and highlight key translational challenges and opportunities. By positioning efferocytosis as a central pathogenic node and a readily targetable mechanism across the spectrum of IMIDs, this review offers a conceptual framework that links fundamental mechanistic insights with clinical translation, thereby laying the groundwork for precision immunomodulatory strategies that aim to restore immune homeostasis rather than merely suppress inflammation.
He Z, Chen N, Zhang Y, Du H, Jie L
Endoscopy & Imaging (non-IUS) (1 papers)
Positioning double-balloon enteroscopy in the diagnostic algorithm for suspected small bowel Crohn’s disease: a retrospective analysis of decision-making at a tertiary referral centre. Frontiers in gastroenterology (Lausanne, Switzerland) | 2026-04-01
Small bowel capsule endoscopy (SBCE) enables non-invasive mucosal assessment of the small bowel, while double-balloon enteroscopy (DBE) allows histological confirmation and therapeutic intervention. Appropriate patient selection is essential to maximise diagnostic yield and minimise unnecessary invasive procedures. We performed a retrospective analysis of patients referred for investigation of suspected small bowel Crohn’s disease over a two-year period at a tertiary referral centre. Demographic data, prior investigations, SBCE findings, and subsequent DBE decisions were recorded. The primary outcome was the decision to proceed to DBE. Secondary outcomes included the diagnostic yields of SBCE and DBE. Multivariate logistic regression was used to identify factors associated with DBE referral. Ninety-eight patients with complete data were included. SBCE was performed as the initial investigation in 90.8%, while 5.5% proceeded directly to DBE for therapeutic or histological indications. The SBCE-to-DBE conversion rate was 30.4%. SBCE alone established or excluded inflammatory bowel disease in 70% of patients. Among those undergoing DBE, Crohn’s disease was confirmed in 21% and excluded in 79%. Increasing age (OR 1.04 per year; 95% CI 1.01-1.07) and diagnostic uncertainty on SBCE (OR 2.0; 95% CI 1.8-3.5) independently predicted DBE referral. SBCE is diagnostic in the majority of patients with suspected small bowel Crohn’s disease and functions effectively as a triage tool. DBE should be reserved for cases requiring histological confirmation, clarification of indeterminate findings, assessment of proximal disease, or therapeutic intervention.
Sheehan T, Hegarty C, Connaughton R, Hall B, Kelly OB
Genetics & Genomics (1 papers)
Mapping adaptive immune responses toward fungal antigens in inflammatory bowel disease using T cell repertoire sequencing and phage-immunoprecipitation sequencing.★ Journal of Crohn’s & colitis | 2026-04
Immune reactivity to the gut mycobiome has been implicated in inflammatory bowel disease (IBD), particularly Crohn’s disease (CD), but the systemic adaptive immune repertoire targeting the gut mycobiome remains incompletely defined. We aimed to map systemic T cell and antibody responses to fungal antigens in IBD. We quantified expansion of fungal-specific T cell receptor β (TRB) clonotypes in the SPARC IBD cohort (CD, n = 1890; ulcerative colitis [UC], n = 914). In participants with paired data (n = 637), we analyzed the gut mycobiome by ITS2 sequencing and linked prevalent amplicon sequence variants (ASVs) to TRB clonotypes using a co-occurrence framework. For humoral immune profiling, we built a Saccharomyces cerevisiae-focused PhIP-Seq library and screened sera from CD (n = 100) and healthy controls (n = 60), including anti-S. cerevisiae antibody+ (ASCA+) and ASCA- individuals. Fungal-specific TRB clonotypes showed greater expansion in CD than UC, including increased responses toward S. cerevisiae and enrichment in more aggressive CD phenotypes. Co-occurrence analysis identified a limited number of TRB-mycobiota associations, consistent with the largely private nature of the gut mycobiome at the ASV level. Antibody reactivity to S. cerevisiae peptides was low relative to common viral and bacterial antigen classes, and no single S. cerevisiae peptide was associated with anti-S. cerevisiae antibody serostatus. CD is associated with expansion of fungal-specific T cell clonotypes, but S. cerevisiae peptide-based PhIP-Seq reveals limited shared IgG reactivity. Broader antigen libraries and complementary assays capturing glycosylated and virulence-associated fungal epitopes will be needed to comprehensively define antifungal humoral immunity in IBD.
Mahdy AKH, ElAbd H, Prinzensteiner M, Jebens H, Sivickis K, Bacher P, Vogl T, Poyet M, Franke A
Guidelines & Consensus (1 papers)
Transitioning to adult care for patients with IBD: the impact of a structured IBD transition program on service engagement.★ Inflammatory bowel diseases | 2026-04-11
The British Society of Gastroenterology recommend use of structured transition programs to improve control of chronic gastrointestinal disease in adolescents. We sought to determine the impact of attending a structured transition program on engagement of patients with inflammatory bowel disease (IBD) services and disease outcomes. We performed a retrospective multicenter study of patients with IBD prior to and post-transfer to adult services. Patients were grouped into those who attended a structured transition program and those who received standard care, transferred with a referral letter. A total of 282 patients were included: 155 patients in our structured transition program cohort and 127 patients in the standard care cohort. Patients who took part in a structured transition program had significantly better engagement with adult IBD services with significantly lower rates of nonattendance at outpatient clinics 1-year post-transfer (12.3% vs 27.2%, P = .002) and significantly lower rates of disengagement with services (4.2% vs 13.1%, P = .015). There were no significant differences seen in rates of biologic failure, need for steroid/surgery or median fecal calprotectin levels between either group. Attending a structured transition program was the only factor that positively impacted engagement with IBD services in a multivariate analysis (OR 4.08, confidence interval 1.41-11.91, P = .01). Structured transition programs in IBD can improve engagement of patients with IBD services with significantly lower rates of disengagement with IBD services seen in our study. Large prospective studies are needed in this field to further investigate this and the impact of these programs on disease outcomes. Our study highlights the importance of a structured transition program for improved engagement with IBD services for patients transferring from pediatric services to adult services. Attendance at a structured transition programs reduces nonattendance at adult IBD outpatient clinics and improves overall engagement with services.
Doherty J, Hurley C, Girod P, Peacock J, Neilan L, Muldowney H, Burke A, Stallard L, Quinn S, Broderick A
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