Journal of Crohn's & colitis最新文献

{"title":"Experience-based reappraisal of the IBD-DCA histopathological scoring system.","authors":"David Egong, Glen Doherty, Kieran Sheahan","doi":"10.1093/ecco-jcc/jjag131","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjag131","url":null,"abstract":"","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":"20 8","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148883057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal transcriptomic analysis of mucosa in ulcerative colitis after anti-tumor necrosis factor withdrawal compared to continued treatment.","authors":"Emma Rapp, Ingrid Prytz Berset, Sinan U Umu, Espen Sønderaal Bækkevold, Karen Sivertsen Utheim, Alexander Dietrich, Markus List, Kjersti Thorvaldsen Hagen, Frode Lerang, Dag Arne Lihaug Hoff, Knut E A Lundin, Frode Lars Jahnsen, Diana Domanska","doi":"10.1093/ecco-jcc/jjag121","DOIUrl":"10.1093/ecco-jcc/jjag121","url":null,"abstract":"<p><strong>Background and aims: </strong>Monoclonal antibodies against tumor necrosis factor (anti-TNF) are effective agents in the treatment of moderate-to-severe ulcerative colitis (UC). It is unclear whether such treatment can safely be discontinued without relapse. This study aimed to identify biomarkers to predict which patients can successfully stop anti-TNF treatment, and to increase our understanding of the pathogenesis of relapse after withdrawal and flare on continued therapy.</p><p><strong>Methods: </strong>We analyzed longitudinal bulk RNA-sequencing data derived from rectal mucosal biopsies from 163 patients in the BIOSTOP study collected at baseline, after 2 years (end of study), and at flares or relapse points.</p><p><strong>Results: </strong>In this cohort, pre-withdrawal transcriptomic profiles did not distinguish patients who later relapsed from those who remained in long-term remission. Longitudinal analysis of patients who relapsed or flared were both characterized by inflammatory gene expression profiles (eg, CXCL9, CXCL10, OSMR, SELE) and changes in cell-type composition typical for active UC (eg, monocytes/macrophages and THY1+ FAP+ PDPN+ activated fibroblasts). Both groups showed enrichment of T-cell-associated transcriptional signatures, including CD8 T-cell-related genes and IL-17-associated pathways. Additionally, both patient groups showed increased expression of targets of alternative therapeutic agents, suggesting potential treatment options for specific patient subgroups.</p><p><strong>Conclusions: </strong>Our findings provide insights into the inflammatory mechanisms driving relapse after anti-TNF withdrawal and flare on continued treatment. The dataset offers a valuable resource for future research to improve personalized treatment strategies in UC.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":"20 8","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13467011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148722870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"2'-Fucosyllactose modulates gut microbiota and systemic metabolism in mild-to-moderate ulcerative colitis: a randomized crossover trial.","authors":"James M Kennedy, Aminda N De Silva, Patricia Sanz Morales, Carlos G Poveda Turrado, Gemma E Walton, Glenn R Gibson","doi":"10.1093/ecco-jcc/jjag120","DOIUrl":"10.1093/ecco-jcc/jjag120","url":null,"abstract":"<p><strong>Background and aims: </strong>The gut microbiota in active ulcerative colitis (UC) differs from that of healthy individuals. Human milk oligosaccharides (HMOs) are prebiotics found in human breastmilk which promote infant health, but are lesser studied in adults. The objective of this study was to assess the impact of the HMO 2'-fucosyllactose (2'-FL) on symptoms, inflammation, gut microbiota, and systemic metabolism in mild-to-moderate UC.</p><p><strong>Methods: </strong>In this randomized, double-blind, placebo-controlled crossover clinical trial, 38 patients with mild-to-moderate UC were randomized to receive 28 days of 2'-FL or 28 days of maltodextrin placebo, followed by washout and crossover. Patient-reported outcome measures, feces, urine, and serum samples were collected before and after each intervention, and after a final washout period.</p><p><strong>Results: </strong>Although no clear treatment effect was observed on conventional clinical indices, 2'-FL exposure was associated with improved patient-reported disease control. 2'-FL significantly modulated the gut microbiota, markedly increasing Bifidobacterium abundance (effect size 4.4%, 95% CI 2.33%-6.47%, P = 6.5 × 10-5). Fecal metabolite profiles showed changes consistent with altered microbial carbohydrate metabolism. Exploratory analyses suggested that age and baseline microbiota may influence clinical and biological responsiveness to 2'-FL.</p><p><strong>Conclusions: </strong>2'-FL exposure was associated with improvement in patient-reported disease control, gut microbiota modulation, and cross-compartmental host-microbial metabolic profile modifications; Clinicaltrials.gov number, NCT06050811.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":"20 8","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13501536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148809707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BRD4 contributes to the cytokine-induced acquisition of an IL-13RA2-positive inflammatory fibroblast phenotype.","authors":"Rachele Frascatani, Mattia Alberto Serra, Andrea Iannucci, Marco Colella, Claudia Maresca, Irene Marafini, Elisabetta Lolli, Giorgia Sena, Andrea Divizia, Andrea Martina Guida, Giuseppe Sigismondo Sica, Giovanni Monteleone","doi":"10.1093/ecco-jcc/jjag128","DOIUrl":"10.1093/ecco-jcc/jjag128","url":null,"abstract":"<p><strong>Background and aims: </strong>Inflammatory bowel diseases (IBDs) are characterized by chronic intestinal inflammation, in which inflammatory fibroblasts contribute to epithelial damage and amplification of mucosal inflammation. However, the molecular mechanisms regulating their pathogenic activity remain incompletely understood. This study investigated the role of the epigenetic reader BRD4 in the differentiation and function of IL-13RA2-expressing inflammatory fibroblasts in IBD.</p><p><strong>Methods: </strong>Single-cell RNA sequencing datasets from IBD patients and controls were analyzed to define BRD4 expression across stromal populations. Protein expression was validated by immunofluorescence and flow cytometry in intestinal tissues and primary fibroblasts. Primary fibroblasts from IBD patients were stimulated with interleukin (IL)-4, IL-13, and tumor necrosis factor-alpha (TNF-α) to induce an inflammatory phenotype, and BRD4 function was assessed using the BRD4-targeting PROTAC AT1. Cytokine and chemokine expression was evaluated by RNA sequencing, real-time polymerase chain reaction (PCR), and ELISA, while neutrophil chemotaxis assays assessed the functional effects of fibroblast-derived mediators.</p><p><strong>Results: </strong>BRD4 was significantly upregulated in inflammatory fibroblasts from IBD patients compared with other stromal subsets and controls. Inflamed tissues showed enrichment of BRD4⁺ and IL-13RA2⁺ fibroblasts. In vitro, cytokine stimulation induced IL-13RA2 expression in the majority of fibroblasts, all of which co-expressed BRD4. BRD4 degradation significantly reduced the proportion of IL-13RA2⁺ fibroblasts. BRD4⁺ fibroblasts exhibited a pro-inflammatory transcriptional profile, including CCL2, CXCL1, CXCL2, IL-11, IL-24, IL-32, and CSF3. Degradation of BRD4 markedly decreased the expression of these mediators and reduced neutrophil migration.</p><p><strong>Conclusions: </strong>BRD4 contributes to cytokine-induced inflammatory activation and pro-inflammatory functions of intestinal fibroblasts in IBD. Targeting BRD4 may represent a potential strategy to modulate stromal cell-driven inflammation.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":"20 8","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13501532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148809756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intestinal cancer risk in Crohn's disease: authors' reply on methods, data integrity, and clinical implications.","authors":"Enrico Altiero Giusto, Paolo Pinton, Carlotta Giorgi, Grazia Serino, Gianluigi Giannelli, Rossella Donghia, Francesco Fiorica","doi":"10.1093/ecco-jcc/jjag097","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjag097","url":null,"abstract":"","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":"20 7","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148427767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid resolution of colon inflammation and microbiome remodeling with vancomycin therapy in a patient with primary sclerosing cholangitis.","authors":"Andre J Sommer, Erica Loon, Alexander Khoruts, Elizabeth S Aby","doi":"10.1093/ecco-jcc/jjag099","DOIUrl":"10.1093/ecco-jcc/jjag099","url":null,"abstract":"","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":"20 7","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148581973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A spatially organized immune-stromal program drives the fissure-to-fistula continuum in Crohn's disease.","authors":"Luca Massimino, Sabrina Nicolò, Tommaso Lorenzo Parigi, Sara Mino, Mattia Bugatti, Francesca Nicola, Nicola Ivan Lorè, Vincenzo Villanacci, Paola Parente, Fabrizio Bossa, Orazio Palmieri, Pierpaolo Sileri, Silvio Danese, Federica Ungaro","doi":"10.1093/ecco-jcc/jjag107","DOIUrl":"10.1093/ecco-jcc/jjag107","url":null,"abstract":"<p><strong>Background & aims: </strong>Fistulizing Crohn's disease represents a severe and disabling complication characterized by transmural inflammation and aberrant tissue remodeling. Although fissures are considered precursors of fistulas, the cellular and molecular mechanisms driving this transition remain poorly defined. We aimed to characterize the spatial immune-stromal interactions underlying fissure formation and progression toward fistula.</p><p><strong>Methods: </strong>Spatial transcriptomics was performed on intestinal surgical specimens from Crohn's disease patients with inflamed tissue, fissures of increasing depth, and entero-enteric fistulas. Spatial data were integrated with single-cell reference and ligand-receptor analysis to define cellular programs and signaling networks across tissue niches.</p><p><strong>Results: </strong>Fissure-associated regions were enriched in inflammatory fibroblasts and inflammatory monocytes, identifying fissures as active immune-stromal niches rather than passive structural defects. Integration with independent single-cell datasets confirmed the association of these signatures with Crohn's disease fistulae, while comparison with non-Crohn's fistulas and ulcerative colitis supported disease specificity. Single-cell-informed pseudotime analysis identified coordinated stromal and myeloid remodeling programs associated with inflammatory fibroblast enrichment and macrophage/LAMP3 + dendritic cell states. Ligand-receptor analysis demonstrated a progressive shift from CXCL12-CXCR4-mediated immune recruitment toward Complement activation and adhesion-mediated retention circuits involving ADGRE5-CD55 and THY1-integrin pathways, defining a spatially organized fistula-associated immune-stromal niche.</p><p><strong>Conclusions: </strong>Fissures represent active immune-stromal niches in which coordinated remodeling programs support the development of the fistula microenvironment. These findings identify early fissure-associated remodeling as a potential therapeutic window and highlight CXCR4, complement, and immune-stromal adhesion pathways as candidate targets to intercept fistula progression in Crohn's disease.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":"20 7","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148611435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative performance of intestinal ultrasound activity indices in pediatric ulcerative colitis: a prospective study.","authors":"Sara Massironi, Giacomo Mulinacci, Giovanna Zuin, Fortunata Civitelli, Lorena Pirola, Elena Tassistro, Viola Carzaniga, Noemi Pistola, Salvatore Oliva, Federica Ferrari, Adriana Balduzzi, Pietro Invernizzi, Marco Emilio Dinelli, Silvio Danese, Marta Maino","doi":"10.1093/ecco-jcc/jjag106","DOIUrl":"10.1093/ecco-jcc/jjag106","url":null,"abstract":"<p><strong>Background & aims: </strong>Endoscopic assessment of disease activity in pediatric ulcerative colitis (UC) is invasive and burdensome. Intestinal ultrasound (IUS) represents a promising noninvasive alternative, but comparative data on IUS-based activity indices in children remain limited. This study evaluated the accuracy of 3 IUS activity indices, the Milan Ultrasound Criteria (MUC), the Ulcerative Colitis-Intestinal Ultrasound (UC-IUS) index, and the Civitelli index, for detecting moderate-to-severe endoscopic activity in pediatric UC and explored the added value of fecal calprotectin (FC) and the Pediatric Ulcerative Colitis Activity Index (PUCAI).</p><p><strong>Methods: </strong>In this prospective bicentric study, 75 pediatric patients with UC underwent IUS within 7 days of colonoscopy. Moderate-to-severe endoscopic activity was defined as Mayo Endoscopic Subscore (MES) ≥ 2. Diagnostic accuracy was assessed using receiver operating characteristic analysis.</p><p><strong>Results: </strong>Moderate-to-severe endoscopic activity was present in 73.3% of patients. All IUS indices significantly discriminated moderate-to-severe from no-to-mild disease (P < .001), with comparable performance (AUC 0.80 [0.68-0.92] for MUC, 0.79 [0.66-0.93] for UC-IUS, and 0.76 [0.62-0.90] for Civitelli). Bowel wall thickness (BWT) alone showed similar accuracy (AUC 0.80 [0.68-0.91]). Models combining IUS indices with FC or PUCAI yielded higher AUC (0.83 and 0.87, respectively), although differences were not statistically significant. Accuracy was highest in severe disease (MES = 3).</p><p><strong>Conclusions: </strong>MUC, UC-IUS, and Civitelli demonstrated comparable accuracy for detecting moderate-to-severe endoscopic activity in pediatric UC. BWT alone performed similarly to composite indices. Combining IUS with FC or PUCAI may provide modest additional diagnostic value, supporting a multimodal, noninvasive approach for disease monitoring and treat-to-target strategies.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":"20 7","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148474962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"\"Magnetic resonance imaging-based simplified MaRIA scores are associated with future surgery in Crohn's disease, but modest correlation with ileo-colonoscopic inflammation limits their utility in clinical trials\" by Bhandari et al.","authors":"Jordi Rimola, Agnès Fernàndez-Clotet, Ingrid Ordás","doi":"10.1093/ecco-jcc/jjag108","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjag108","url":null,"abstract":"","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":"20 7","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148586526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to 5 papers to correct the issue number.","authors":"","doi":"10.1093/ecco-jcc/jjag093","DOIUrl":"10.1093/ecco-jcc/jjag093","url":null,"abstract":"","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":"20 7","pages":""},"PeriodicalIF":8.7,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13385341/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148537898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}