Inflammatory Bowel Diseases最新文献

{"title":"Branched-Chain Amino Acids Exacerbate Colitis Progression by Lowering Colonic Fumarate Levels.","authors":"Ana Mendes-Frias, Maria C Vieira, Marta Araújo, Cláudio Duarte-Oliveira, Simon Feys, Consuelo Micheli, Joana Gaifem, Luís Gafeira Gonçalves, Nuno S Osório, Adhemar Longatto-Filho, António Gil Castro, Egídio Torrado, Cristina Cunha, Agostinho Carvalho, Iola F Duarte, Nuno A Silva, Fernando Rodrigues, Ricardo Silvestre","doi":"10.1093/ibd/izaf125","DOIUrl":"https://doi.org/10.1093/ibd/izaf125","url":null,"abstract":"<p><strong>Background: </strong>Ulcerative colitis (UC) is a gastrointestinal inflammatory condition with an unclear etiology. Recent findings suggest that metabolites play a pivotal role in promoting intestinal health. We have previously observed a significant enrichment in colonic branched-chain amino acids (BCAAs) in resistant mice to colitis suggesting the potential role of these metabolites in UC development.</p><p><strong>Methods: </strong>C57BL6/J mice underwent a 20-day BCAA supplementation regimen, followed by induction of colitis using dextran sulfate sodium (DSS). Disease activity index (DAI), immune cell profiling, and histological and transcriptomic analysis were evaluated. 16S rRNA sequencing and metabolomic profiling of stool extracts were performed. Additionally, mice were treated with dimethyl fumarate (DMF) post-supplementation to explore therapeutic interventions.</p><p><strong>Results: </strong>BCAA supplementation exacerbated colitis severity in mice, as evidenced by worsened DAI, increased histological damage, and significant alterations in immune cell populations, including decreased type 3 innate lymphoid cells and increased Th17 and regulatory T cells. Microbiota analysis showed a shift toward a decreased abundance of Lactobacillus spp. and an increase in pathobionts. Metabolomic profiling indicated significantly reduced colonic fumarate levels and increased pro-inflammatory metabolites. DMF treatment attenuated BCAA-induced pro-inflammatory phenotype, improved disease outcomes, and modulated the immune response in a microbiome-dependent manner.</p><p><strong>Conclusions: </strong>BCAA supplementation exacerbates DSS-induced colitis in mice. This effect is mediated by detrimental changes in gut microbiota composition and metabolome. DMF treatment shows promise to mitigate these adverse effects, suggesting potential therapeutic avenues to manage BCAA-induced colitis exacerbation and reinforcing the role of microbiome in UC. These findings underscore the caution needed with the use of BCAAs during inflammatory conditions.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient-Specific Regulatory Network Rewiring in Inflammatory Bowel Disease: How Genetic Polymorphisms Divert Incoming Signals and Contribute to Disease Pathogenesis.","authors":"Balazs Bohar, John P Thomas, Yufan Liu, Johanne Brooks-Warburton, Bram Verstockt, Nick Powell, Tamas Korcsmaros, Dezso Modos","doi":"10.1093/ibd/izaf173","DOIUrl":"https://doi.org/10.1093/ibd/izaf173","url":null,"abstract":"<p><strong>Background: </strong>Intestinal cells receive incoming signals from neighboring cells and microbial communities. Upstream signaling pathways transduce these signals to reach transcription factors (TFs) that regulate gene expression. In inflammatory bowel disease (IBD), most single nucleotide polymorphisms (SNPs) are in non-coding genomic regions containing TF binding sites. These SNPs can alter TF binding affinity, leading to regulatory shifts: TFs may lose or gain binding sites, causing a significant rewiring of the incoming signals regulating gene expression. Understanding this rewiring offers critical insights into the cellular mechanisms driving IBD pathogenesis.</p><p><strong>Methods: </strong>To investigate this rewiring, we developed a systems genomics pipeline and analyzed individual genotype data from 2636 IBD patients to infer the incoming signals affecting patient-specific gene regulatory networks. Our in silico approach predicted changes in the repertoire of TFs binding to genomic loci due to IBD-associated non-coding SNPs in each patient compared to healthy controls. By functionally annotating the TFs in disease and healthy states, we highlighted the rewiring of upstream signaling pathways that may arise due to IBD-associated SNPs.</p><p><strong>Results: </strong>We revealed that diverse non-coding SNP combinations in IBD patients lead to functional switches from healthy signals to disease-associated signals, capturing patient heterogeneity while uncovering common upstream regulators driving disease pathogenesis. Notably, rewired incoming signals belonged to key functional processes such as pro-inflammatory immune responses, epithelial barrier dysfunction, stress responses, wound healing, and antimicrobial defense pathways.</p><p><strong>Conclusions: </strong>In summary, this work highlights the importance of personalized investigation of signaling processes upstream of genetic polymorphisms to gain a more comprehensive understanding of IBD pathogenesis.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"When to Switch to Subcutaneous Infliximab? The RE-WATCH Multicenter Study.","authors":"Lorenzo Bertani, Davide Giuseppe Ribaldone, Fabrizio Bossa, Maria Guerra, Monica Annese, Raffaele Manta, Angelo Armandi, Gian Paolo Caviglia, Alessia Todeschini, Angela Variola","doi":"10.1093/ibd/izaf172","DOIUrl":"https://doi.org/10.1093/ibd/izaf172","url":null,"abstract":"<p><strong>Background: </strong>The infliximab (IFX) biosimilar, CT-P13, is available as an intravenous (IV) and subcutaneous (SC) formulation. Although current indications allow the transition from IV CT-P13 to SC CT-P13 after two IV administrations, some clinicians prefer to postpone switching until stable clinical remission has been achieved.</p><p><strong>Methods: </strong>We evaluate the endoscopic response, treatment persistence, clinical remission, endoscopic remission, and safety profile after one year of treatment with IFX in patients switched from IV to SC after 6 weeks (early switch group) or after 6 months (late switch group).</p><p><strong>Results: </strong>There were no statistical differences between the two groups after one year in terms of endoscopic response (71.4% vs 70.8%, P = .95), steroid-free clinical remission (62.5% vs 68.7%, P = .51), or IFX retention rate (75.0% vs 66.7%, P = .35). We observed higher endoscopic remission rates in early switch patients as compared to late switch patients; however, this trend was not significant (69.6% vs 52.1%, P = .07). A return to IV-IFX was required in 1 of 43 early switch patients and in 3 of 44 late switch patients (2.3% vs 6.8%, P = .31). Clinical indexes, fecal calprotectin and C-reactive protein (CRP) levels significantly decreased after one year regardless of group. Adverse events were also comparable between groups (4.5% vs 8.3%, P = .46).</p><p><strong>Conclusions: </strong>Our study has shown that early switch from IV-IFX to SC-IFX at 6 weeks is effective in terms of clinical and endoscopic remission at one year yielding similar results to late switch at 6 months.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Research: Disparities in Outcomes for Patients With Inflammatory Bowel Disease at a Private vs Public Hospital in New York City.","authors":"Sharon Klein, Barathi Sivasailam, Madeline Alizadeh, Lisa Malter, Jordan E Axelrad","doi":"10.1093/ibd/izaf174","DOIUrl":"https://doi.org/10.1093/ibd/izaf174","url":null,"abstract":"<p><strong>Background: </strong>In patients with inflammatory bowel disease (IBD), social determinants of health contribute to health inequalities. We aimed to compare patients with IBD treated at a private nonprofit vs public hospital in New York City.</p><p><strong>Methods: </strong>We performed a retrospective study of adult patients with Crohn's disease or ulcerative colitis with established IBD care. Patient demographics, disease characteristics, healthcare utilization, treatment modalities, and clinical outcomes were collected. Using a series of linear mixed and logistic models, the differences between care at a private nonprofit vs public hospital were assessed while controlling for factors that differed between them.</p><p><strong>Results: </strong>Our study included 418 patients with IBD, 209 from each hospital. Compared with public hospital patients, private hospital patients were more likely to be White, be non-Hispanic, and have private insurance (all P = .0005) and less likely to face housing instability (P < .0001), face unemployment (P = .0004), be current smokers (P = .03), or be foreign born (P < .0001). Patients at the private hospital were more likely to have multiple anti-tumor necrosis factor (P = .0001) and biologic use (P < .0001). Public hospital patients were less likely to be considered endoscopically adherent (odds ratio [OR], 0.377; P = .001) and more likely to visit the emergency department (OR, 5.01; P < .0001) and be hospitalized (OR, 1.92; P = .05).</p><p><strong>Conclusions: </strong>Our study is the first to identify significant differences in patient demographics, disease phenotype, treatments and clinical outcomes between patients treated for IBD at a private nonprofit vs public hospital. Our data suggest that social determinants of health drive disparities in the utilization of healthcare facilities.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145006133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Impact of Sarcopenia on Clinical Outcomes in Pediatric Crohn's Disease.","authors":"Giulia D'Arcangelo, Delia De Mitri, Ludovica Busato, Lorenza Bottino, Francesca Maccioni, Andrea Verrino, Marina Aloi","doi":"10.1093/ibd/izaf193","DOIUrl":"https://doi.org/10.1093/ibd/izaf193","url":null,"abstract":"<p><strong>Background: </strong>The effect of sarcopenia on clinical outcomes in children with Crohn's disease (CD) is unknown. We investigated whether sarcopenia at the diagnosis impacts the outcomes of children with CD.</p><p><strong>Methods: </strong>This was a retrospective, single-center, case-control study of newly diagnosed children with CD undergoing magnetic resonance (MR) within 1 month from the diagnosis, from 2011 to 2022. Sarcopenia was assessed by measuring total psoas muscle area (tPMA) at L3-L4 level on the MR and defined as z-score values ≤2 SDs. Children with and without sarcopenia were compared for the risk of disease flares, CD-related hospitalization, complications, need for step-up treatment, and courses of steroids over a 2-year follow-up.</p><p><strong>Results: </strong>Seventy-eight children were included (median age 10.7 years), 46 (59%) with sarcopenia and 32 (41%) without. The risk of clinical relapse was higher in patients with sarcopenia at 6 [19.5% vs 3%, odds ratio (OR) 7.5 (95% CI, 1.5-85)] and 12 months [30% vs 6%, OR 6.5 (95% CI, 1.4-30.4)]. Kaplan-Meier analysis showed lower survival free from relapses in children with sarcopenia (log rank P = .01, hazard ratio 2.7, 95% CI, 1.4-4.5). Multivariate analysis identified sarcopenia as independent predictors of clinical relapses (OR 1.7, 95% CI, 1-3.1, P = .045). No other independent predictor of unfavorable outcome was detected.</p><p><strong>Conclusions: </strong>The presence of sarcopenia at the diagnosis increases the risk of clinical relapses in the first year of diagnosis. Magnetic resonance evaluation of the tPMA could therefore help identify children at higher risk of worse outcomes.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145006199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Fecal Microbial Community Profiling Allows Discrimination of Phenotype and Treatment Response in Pediatric Crohn's Disease and Ulcerative Colitis-An International Meta-Analysis.","authors":"","doi":"10.1093/ibd/izaf200","DOIUrl":"10.1093/ibd/izaf200","url":null,"abstract":"","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145000438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter to the Editor Regarding \"Real-World Comparison of Effectiveness, Treatment Persistence, and Safety of First-Line Advanced Therapies at 1 Year for Ulcerative Proctitis\".","authors":"Joaquín Borrás-Blasco, Alejandro Valcuende-Rosique, Silvia Cornejo-Uixeda","doi":"10.1093/ibd/izaf161","DOIUrl":"10.1093/ibd/izaf161","url":null,"abstract":"","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144952849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computer-Aided Detection Colonoscopy for Surveillance in IBD Patients: Insights from a Single-Center Experience.","authors":"Adam Goldman, Levy Idan, Shomron Ben-Horin, Uri Kopylov, Asaf Levartovsky","doi":"10.1093/ibd/izaf180","DOIUrl":"10.1093/ibd/izaf180","url":null,"abstract":"<p><strong>Objectives: </strong>The real-world efficacy of computer-aided detection (CADe) in improving surveillance colonoscopy performance for patients with inflammatory bowel disease (IBD) has not been established.</p><p><strong>Methods: </strong>A retrospective, single-center study of surveillance colonoscopies in patients with IBD. Only colonoscopies indicated for surveillance, with adequate preparation and documented cecal intubation, were included. The study compared the collective adenoma detection rate (ADR) between the periods before (pre-CADe) (June 2020 to June 2021) and after (July 2021 to September 2022) the introduction of the CADe in all endoscopy units. An adjusted ADR was calculated using a multivariable logistic regression model.</p><p><strong>Results: </strong>The study included 225 eligible colonoscopies performed during the pre-CADe period and 750 during the CADe period. Neoplastic lesions or colorectal cancer were detected in 13 (5.8%) of 225 procedures in the pre-CADe period and 27 (3.6%) of 750 procedures during the CADe period. The collective ADR was 5.2% (95% confidence interval, 3.9-6.6) in the pre-CADe period and 3.8% (95% confidence interval, 1.1-6.5) -following CADe implementation (P = .315). Subgroup analyses stratified by endoscopist experience, IBD type, and procedure timing (daytime vs after hours) corroborated a similar nonsignificant declining trend in ADR after CADe introduction.</p><p><strong>Conclusions: </strong>In a real-world, single-center experience, the introduction of CADe did not improve neoplasms detection in patients with IBD and was associated with a nonsignificant decline in ADR. These findings call into question the utility of generic CADe systems in IBD surveillance and emphasize the need to foster IBD-specific CADe systems, as well as addressing challenges arising from physician-artificial intelligence interactions.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144952734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional Profiling Demonstrates That a Sulfide-Reducing Diet Achieves Microenvironmental Targets in Ulcerative Colitis.","authors":"Alice S Day, Rachael Slater, Remy B Young, Reuben Z Wheeler, Vanessa R Marcelino, Natasha K Maddigan, Samuel C Forster, Samuel P Costello, Wendy Uylaki, Chris S J Probert, Jane M Andrews, Chu K Yao, Peter R Gibson, Robert V Bryant","doi":"10.1093/ibd/izaf177","DOIUrl":"10.1093/ibd/izaf177","url":null,"abstract":"<p><strong>Background: </strong>As a dietary approach to reducing inflammation in ulcerative colitis, the 4-SURE (4 Strategies to Sulfide Reduction) diet was designed to correct pathogenic alterations of excessive protein fermentation and hydrogen sulfide (H2S) production in the distal colon. We aimed to perform a deep functional analysis (microbial and metabolomic) of the feces of 28 adults with mild-moderately active ulcerative colitis who adhered to the 4-SURE diet over 8 weeks to explore whether the 4-SURE diet could modulate the intraluminal environment as intended.</p><p><strong>Methods: </strong>Fecal samples were collected at week 0 and 8 of dietary intervention, processed and aliquoted. Metagenomic sequencing was undertaken to identify changes in H2S-metabolizing genes, while gas chromatography-mass spectrometry was used to analyze fecal volatile organic compounds and H2S production.</p><p><strong>Results: </strong>The 4-SURE diet significantly increased alpha diversity between weeks 0 and 8. By random forest plot classifier, the abundance of taxonomic groups comprising known H2S-producing genera were markedly lower at week 8, specifically Odoribacter and Peptostreptococcaceae, and were of highest importance in discriminating between before- and after-diet samples. The capacity for bacterial H2S metabolism was altered with diet, with differences in 12 of 67 analyzed sulfur-metabolizing genes identified. H2S production and indole, a specific marker of protein fermentation, were significantly decreased due to the diet.</p><p><strong>Conclusions: </strong>Here, we demonstrate that the objectives of the 4-SURE diet were fulfilled. This application of deep functional analysis to a dietary intervention study is novel and highlights an exemplar framework for including microbial and metabolomic biomarkers of pathogenic relevance in the analysis of therapeutic diet strategies. (Australian New Zealand Clinical Trials Registry, Number: ACTRN12619000063112).</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144952760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Novel mRNA Signature for Anti-TNF-α Therapy Primary Response in Patients With Ulcerative Colitis.","authors":"","doi":"10.1093/ibd/izaf140","DOIUrl":"10.1093/ibd/izaf140","url":null,"abstract":"","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":"2614"},"PeriodicalIF":4.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}