Journal of Crohn's & colitis最新文献

{"title":"Genome-wide DNA Methylome and Transcriptome Profiling Reveals Key Genes Involved in the Dysregulation of Adipose Stem Cells in Crohn's Disease.","authors":"Diandra Monfort-Ferré, Albert Boronat-Toscano, José-Francisco Sánchez-Herrero, Aleidis Caro, Margarita Menacho, Irene Vañó-Segarra, Marc Martí, Beatriz Espina, Raquel Pluvinet, Lidia Cabrinety, Carme Abadia, Miriam Ejarque, Cati Nuñez-Roa, Elsa Maymo-Masip, Lauro Sumoy, Joan Vendrell, Sonia Fernández-Veledo, Carolina Serena","doi":"10.1093/ecco-jcc/jjae072","DOIUrl":"10.1093/ecco-jcc/jjae072","url":null,"abstract":"<p><strong>Background and aims: </strong>Crohn's disease [CD] is characterised by the expansion of mesenteric adipose tissue [MAT], named creeping fat [CF], which seems to be directly related to disease activity. Adipose-stem cells [ASCs] isolated from the CF of patients with CD are extremely pro-inflammatory, which persists during disease remission. We hypothesised that the dysfunctional ASCs in CD accumulate epigenetic modifications triggered by the inflammatory environment, that could serve as molecular markers.</p><p><strong>Methods: </strong>Genome-wide DNA methylome and transcriptome profiling were performed in ASCs isolated from MAT biopsies of patients with active and inactive disease and from non-Crohn's disease patients [non-CD]. A validation cohort was used to test the main candidate genes via quantitative polymerase chain reaction in other fat depots and immune cells.</p><p><strong>Results: </strong>We found differences in DNA methylation and gene expression between ASCs isolated from patients with CD and from non-CD subjects, but we found no differences related to disease activity. Pathway enrichment analysis revealed that oxidative stress and immune response were significantly enriched in active CD, and integration analysis identified MAB21L2, a cell fate-determining gene, as the most affected gene in CD. Validation analysis confirmed the elevated gene expression of MAB21L2 in MAT and in adipose tissue macrophages in active CD. We also found a strong association between expression of the calcium channel subunit gene CACNA1H and disease remission, as CACNA1H expression was higher in ASCs and MAT from patients with inactive CD, and correlates negatively with C-reactive protein in peripheral blood mononuclear cells.</p><p><strong>Conclusion: </strong>We identified a potential gene signature of CD in ASCs obtained from MAT. Integration analysis highlighted two novel genes demonstrating a negative correlation between promoter DNA methylation and transcription: one linked to ASCs in CD [MAB21L2] and the other [CACNA1H] related to disease remission.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140924211","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":"Measurement Is Necessary But Not Sufficient to Improve Quality of Care for Patients With Inflammatory Bowel Disease.","authors":"Corey A Siegel, Gil Y Melmed","doi":"10.1093/ecco-jcc/jjae119","DOIUrl":"10.1093/ecco-jcc/jjae119","url":null,"abstract":"","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142044273","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":"Influence of Vitamin D Receptor Signalling and Vitamin D on Colonic Epithelial Cell Fate Decisions in Ulcerative Colitis.","authors":"Lauge Kellermann, Stine Lind Hansen, Grzegorz Maciag, Agnete Marie Granau, Jens Vilstrup Johansen, Joji Marie Teves, Raul Bardini Bressan, Marianne Terndrup Pedersen, Christoffer Soendergaard, Astrid Moeller Baattrup, Alexander Hammerhøj, Lene Buhl Riis, John Gubatan, Kim Bak Jensen, Ole Haagen Nielsen","doi":"10.1093/ecco-jcc/jjae074","DOIUrl":"10.1093/ecco-jcc/jjae074","url":null,"abstract":"<p><strong>Background and aims: </strong>Epidemiological studies have shown that subnormal levels of vitamin D (25[OH]D) are associated with a more aggravated clinical course of ulcerative colitis [UC]. Despite an increased focus on the therapeutic importance of vitamin D and vitamin D receptor [VDR] signalling, the mechanisms underlying the effects of the vitamin D-VDR axis on UC remain elusive. Therefore, we aimed to investigate whether exposure to active vitamin D (1,25[OH]2D3/VDR) signalling in human organoids could influence the maintenance of the colonic epithelium.</p><p><strong>Methods: </strong>Intestinal VDR expression was studied by immunohistochemistry, RNA expression arrays, and single-cell RNA sequencing of colonic biopsy specimens obtained from patients with UC and healthy individuals. To characterise the functional and transcriptional effects of 1,25[OH]2D3, we used patient-derived colonic organoids. The dependency of VDR was assessed by knocking out the receptor with CRISPR/Cas9.</p><p><strong>Results: </strong>Our results suggest that 1,25[OH]2D3/VDR stimulation supports differentiation of the colonic epithelium and that impaired 1,25[OH]2D3/VDR signalling thereby may compromise the structure of the intestinal epithelial barrier, leading to flares of UC. Furthermore, a transcriptional response to VDR activity was observed primarily in fully differentiated cells at the top of the colonic crypt, and this response was reduced during flares of UC.</p><p><strong>Conclusions: </strong>We identified an important role of vitamin D signalling in supporting differentiated cell states in the human colonic epithelium, and thereby maintenance of the intestinal barrier integrity. This makes the vitamin D-VDR signalling axis an interesting target for therapeutic efforts to achieve and maintain remission in patients with UC.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11479711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140924214","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":"ECCO Guidelines on Therapeutics in Crohn's Disease: Medical Treatment.","authors":"Hannah Gordon, Silvia Minozzi, Uri Kopylov, Bram Verstockt, María Chaparro, Christianne Buskens, Janindra Warusavitarne, Manasi Agrawal, Mariangela Allocca, Raja Atreya, Robert Battat, Dominik Bettenworth, Gabriele Bislenghi, Steven Ross Brown, Johan Burisch, María José Casanova, Wladyslawa Czuber-Dochan, Joline de Groof, Alaa El-Hussuna, Pierre Ellul, Catarina Fidalgo, Gionata Fiorino, Javier P Gisbert, João Guedelha Sabino, Jurij Hanzel, Stefan Holubar, Marietta Iacucci, Nusrat Iqbal, Christina Kapizioni, Konstantinos Karmiris, Taku Kobayashi, Paulo Gustavo Kotze, Gaetano Luglio, Christian Maaser, Gordon Moran, Nurulamin Noor, Konstantinos Papamichael, Georgios Peros, Catherine Reenaers, Giuseppe Sica, Rotem Sigall-Boneh, Stephan R Vavricka, Henit Yanai, Pär Myrelid, Michel Adamina, Tim Raine","doi":"10.1093/ecco-jcc/jjae091","DOIUrl":"10.1093/ecco-jcc/jjae091","url":null,"abstract":"","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141328249","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":"Faecal Transplantation for Ulcerative Colitis From Diet Conditioned Donors Followed by Dietary Intervention Results in Favourable Gut Microbial Profile Compared to Faecal Transplantation Alone.","authors":"Haim Leibovitzh, Chen Sarbagili Shabat, Ayal Hirsch, Eran Zittan, Maria Chiara Mentella, Valentina Petito, Nathaniel Aviv Cohen, Yulia Ron, Naomi Fliss Isakov, Jorge Pfeffer, Michal Yaakov, Caterina Fanali, Laura Turchini, Luca Masucci, Gianluca Quaranta, Nitzan Kolonimos, Anastasia Godneva, Adina Weinberger, Franco Scaldaferri, Nitsan Maharshak","doi":"10.1093/ecco-jcc/jjae062","DOIUrl":"10.1093/ecco-jcc/jjae062","url":null,"abstract":"<p><strong>Background and aims: </strong>Several faecal microbial transplantation [FMT] approaches for ulcerative colitis [UC] have been investigated with conflicting results. We have recently published the clinical outcomes from the CRAFT UC Trial using FMT with the UC Exclusion Diet [UCED], compared with FMT alone. Here we aimed to compare the two FMT strategies in terms of microbial profile and function.</p><p><strong>Methods: </strong>Subjects recruited to the CRAFT UC study with available pre- and post-intervention faecal samples were included. Donors received diet conditioning for 14 days based on the UCED principles. Group 1 received single FMT by colonoscopy [Day 1] and enemas [Days 2 and 14] without donors' dietary conditioning [N = 11]. Group 2 received FMT but with donors' dietary pre-conditioning and UCED for the patients [N = 10]. Faecal samples were assessed by DNA shotgun metagenomic sequencing.</p><p><strong>Results: </strong>Following diet conditioning, donors showed depletion in metabolic pathways involved in biosynthesis of sulphur-containing amino acids. Only Group 2 showed significant shifts towards the donors' microbial composition [ADONIS: R2 = 0.15, p = 0.008] and significantly increased Eubacterium_sp_AF228LB post-intervention [β-coefficient 2.66, 95% confidence interval 2.1-3.3, q < 0.05] which was inversely correlated with faecal calprotectin [rho = -0.52, p = 0.035]. Moreover, pathways involved in gut inflammation and barrier function including branched chain amino acids were enriched post-intervention in Group 2 and were significantly inversely correlated with faecal calprotectin.</p><p><strong>Conclusion: </strong>FMT from diet conditioned donors followed by the UCED led to microbial alterations associated with favourable microbial profiles which correlated with decreased faecal calprotectin. Our findings support further exploration of the additive benefit of dietary intervention for both donors and patients undergoing FMT as a potential treatment of UC.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140891565","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":"Real-World Comparison of the Effectiveness between Ustekinumab and Vedolizumab in Patients with Ulcerative Colitis Exposed to at least One Anti-TNF Agent.","authors":"Mathurin Fumery, Mélanie Serrero, Guillaume Bouguen, Aurélien Amiot, Romain Altwegg, Maria Nachury, Lucine Vuitton, Xavier Treton, Ludovic Caillo, Bruno Pereira, Antony Buisson","doi":"10.1093/ecco-jcc/jjae063","DOIUrl":"10.1093/ecco-jcc/jjae063","url":null,"abstract":"<p><strong>Background: </strong>Both vedolizumab and ustekinumab can be considered for the treatment of ulcerative colitis [UC], but head-to-head trials are lacking.</p><p><strong>Aim: </strong>We aimed to compare the effectiveness of vedolizumab and ustekinumab after anti-tumour necrosis factor [anti-TNF] failure in UC patients.</p><p><strong>Patients and methods: </strong>In this multicentre study, we included consecutive adult patients with UC, with partial Mayo score >2 and prior anti-TNF exposure, treated with vedolizumab or ustekinumab between January 2019 and August 2022. Comparisons were performed using propensity score analyses [inverse probability of treatment weighting].</p><p><strong>Results: </strong>Among a total of 293 patients included, 151 and 142 received vedolizumab and ustekinumab, respectively. After propensity score analysis, steroid-free clinical remission [SFCR] [partial Mayo score ≤2] was achieved at week 16 in 38.0% and 40.3% of patients treated with vedolizumab and ustekinumab, respectively (adjusted odds ratio [aOR] = 1.11, 95% confidence interval [0.39-3.13], p = 0.85). Rates of SFCR in patients exposed to one, two, and three lines of biologics/small molecules among patients treated with vedolizumab and ustekinumab were respectively 53.3% vs 62.1% [p = 0.52], 44.4% vs 33.8% [p = 0.52], and 2.6% vs 19.1% [p = 0.027]. Endoscopic remission [SFCR and endoscopic Mayo score ≤1] and histological remission [SFCR, endoscopic remission, and Nancy histological index ≤1] at week 16 were achieved in respectively 5.3% vs 17.5% (aOR = 3.77 [1.25-11.36], p = 0.018) and 2.1% vs 11.1% (aOR = 5.85 [1.47-23.30], p = 0.012) in the vedolizumab and ustekinumab groups. No difference regarding the risk of drug discontinuation between the two groups (aHR = 1.03 [0.51-2.08], p = 0.92) was observed. While no factor was identified for vedolizumab, primary failure to at least one biologic/small molecule (OR = 0.31 [0.11-0.82], p = 0.018) was significantly associated with a decreased rate of SFCR among patients treated with ustekinumab.</p><p><strong>Conclusion: </strong>While no difference in terms of short-term clinical remission was observed, ustekinumab appears to be more effective than vedolizumab in inducing endoscopic and histological remission at week 16 after failure of anti-TNFs in UC.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140924199","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 Core Outcome Set for Inflammatory Bowel Diseases: Development and Recommendations for Implementation in Clinical Practice Through an International Multi-stakeholder Consensus Process.","authors":"Liselotte Fierens, Nicholas Carney, Gottfried Novacek, C Janneke van der Woude, Britta Siegmund, Francesc Casellas, Natalia Borruel, Anouk S Huberts, Elena Sonnenberg, Nathalie Gerold, Christian Primas, Charlotte R H Hedin, Tanja Stamm, Mette Julsgaard, Gionata Fiorino, Simona Radice, Michela Luciana Luisa Zini, Evelyn Gross, Cornelia Sander, Ingrid Arijs, Vasiliki-Rafaela Vakouftsi, Tunde Koltai, Health Outcomes Observatory H O Patient Advisory Board For Inflammatory Bowel Diseases, Health Outcomes Observatory H O Steering Committee, Iliàs Charlafti, Marc Ferrante","doi":"10.1093/ecco-jcc/jjad195","DOIUrl":"10.1093/ecco-jcc/jjad195","url":null,"abstract":"<p><strong>Background and aims: </strong>Standardising health outcome measurements supports delivery of care and enables data-driven learning systems and secondary data use for research. As part of the Health Outcomes Observatory [H2O] initiative, and building on existing knowledge, a core outcome set [COS] for inflammatory bowel diseases [IBD] was defined through an international modified Delphi method.</p><p><strong>Methods: </strong>Stakeholders rated 90 variables on a 9-point importance scale twice, allowing score modification based on feedback displayed per stakeholder group. Two consecutive consensus meetings were held to discuss results and formulate recommendations for measurement in clinical practice. Variables scoring 7 or higher by ≥80% of the participants, or based on consensus meeting agreement, were included in the final set.</p><p><strong>Results: </strong>In total, 136 stakeholders (45 IBD patients [advocates], 74 health care professionals/researchers, 13 industry representatives, and four regulators) from 20 different countries participated. The final set includes 18 case-mix variables, three biomarkers [haemoglobin to detect anaemia, C-reactive protein and faecal calprotectin to detect inflammation] for completeness, and 28 outcomes (including 16 patient-reported outcomes [PROs] and one patient-reported experience). The PRO-2 and IBD-Control questionnaires were recommended to collect disease-specific PROs at every contact with an IBD practitioner, and the Subjective Health Experience model questionnaire, PROMIS Global Health and Self-Efficacy short form, to collect generic PROs annually.</p><p><strong>Conclusions: </strong>A COS for IBD, including a recommendation for use in clinical practice, was defined. Implementation of this set will start in Vienna, Berlin, Barcelona, Leuven, and Rotterdam, empowering patients to better manage their care. Additional centres will follow worldwide.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138465232","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":"The circulating methylome in childhood-onset inflammatory bowel disease.","authors":"Alexandra Noble, Alex Adams, Jan Nowak, Guo Cheng, Komal Nayak, Aisling Quinn, Mark Kristiansen, Rahul Kalla, Nicholas T Ventham, Federica Giachero, Chamara Jayamanne, Richard Hansen, Georgina L Hold, Emad El-Omar, Nicholas M Croft, David Wilson, R Mark Beattie, James J Ashton, Matthias Zilbauer, Sarah Ennis, Holm H Uhlig, Jack Satsangi","doi":"10.1093/ecco-jcc/jjae157","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjae157","url":null,"abstract":"<p><p>The genetic contribution to inflammatory bowel disease (IBD) encompassing both Crohn's disease (CD) and ulcerative colitis (UC), accounts for around 20% of disease variance, highlighting the need to characterise environmental and epigenetic influences. Recently considerable progress has been made in characterising the adult methylome, in epigenome-wide association studies. We report detailed analysis of the circulating methylome in 86 patients with childhood-onset CD,UC and 30 controls using the Illumina Infinium Human MethylationEPIC platform. We derive and validate a 4-probe methylation biomarker (RPS6KA2, VMP1, CFI and ARHGEF3), with specificity and high diagnostic accuracy for paediatric IBD in UK and North American cohorts (AUC 0.90-0.94). Significant epigenetic age acceleration is present at diagnosis, with the greatest observed in CD patients. Cis-MeQTL analysis identifies genetic determinants underlying epigenetic alterations notably within the HLA 6p22.1-p21.33 region. Passive smoking exposure is associated with the development of UC rather than CD contrary to previous findings. These data provide new insights into epigenetic alterations in IBD and illustrate the reproducibility and translational potential of epigenome-wide association studies in complex diseases.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142373933","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":"Crohn's disease and ulcerative colitis share two molecular subtypes with different mechanisms and drug response.","authors":"Jing Wang, Heath Guay, Dan Chang","doi":"10.1093/ecco-jcc/jjae152","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjae152","url":null,"abstract":"<p><strong>Background and aims: </strong>Several therapies have been approved to treat crohn's disease (CD) and ulcerative colitis (UC), indicating that both diseases may share the same molecular subtypes. The aim of this study is to identify shared patient subtypes with common molecular drivers of disease.</p><p><strong>Methods: </strong>Five public datasets with 406 CD and 421 UC samples were integrated to identify molecular subtypes. Then, the patient labels from six independent datasets and eight treatment datasets were predicted for validating subtypes and identifying the relationship with response status of corticosteroids, infliximab, vedolizumab, and ustekimumab.</p><p><strong>Results: </strong>Two molecular subtypes were identified from the training datasets, in which CD and UC patients were relatively evenly represented in each subtype. We found six S1-specific gene modules related to innate/adaptive immune responses and tissue remodeling and nine S1-specific cell types (cycling T, Tregs, cd8+ lamina propria, follicular B, cycling B plasma, inflammatory monocytes, inflammatory fibroblast, and post-capillary venules). Subtype S2 was associated with three modules related to metabolism functions and four cell types (immature enterocytes, transit amplifying, immature goblet and WNT5B+). The subtypes can be replicated in six independent datasets based on a 20-gene classifier. Furthermore, response rates to four treatments in subtype S2 were significantly higher than those in subtype S1.</p><p><strong>Conclusions: </strong>This study discovered and validated a robust transcriptome-based molecular classification shared by CD and UC and built a 20-gene classifier. Because two subtypes have different molecular mechanisms and drug response, our classification may aid interpretation of heterogeneous molecular and clinical information in IBD patients.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142368047","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":"The intestinal mucin isoform landscape reveals region-specific biomarker panels for inflammatory bowel disease patient stratification.","authors":"Wout Arras, Tom Breugelmans, Baptiste Oosterlinck, Joris G De Man, Surbhi Malhotra-Kumar, Steven Abrams, Steven Van Laere, Elisabeth Macken, Michaël Somers, Aranzazu Jauregui-Amezaga, Benedicte Y De Winter, Annemieke Smet","doi":"10.1093/ecco-jcc/jjae155","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjae155","url":null,"abstract":"<p><strong>Background and aims: </strong>Mucosal healing is considered as a key therapeutic endpoint in inflammatory bowel diseases (IBD) and comprises endoscopic improvement of inflammation without taking barrier healing into account. Mucins are critical components of the mucosal barrier function that give rise to structurally diverse isoforms. Unraveling disease-associated mucin isoforms that could act as an indication for barrier function would greatly enhance IBD management.</p><p><strong>Methods: </strong>We present the intestinal mucin RNA isoform landscape in IBD and control patients using a targeted mucin isoform sequencing approach on a discovery cohort (n = 106). Random Forest modeling (n = 1683 samples) with external validation (n = 130 samples) identified unique mucin RNA isoform panels that accurately stratified IBD patients in multiple subpopulations based on inflammation, IBD subtype (Crohn's disease (CD), ulcerative colitis (UC)), and anatomical location of the intestinal tract (i.e. ileum, proximal colon, distal colon, rectum).</p><p><strong>Results: </strong>Particularly, the mucin RNA isoform panels obtained from the inflamed UC and CD distal colon showed high performance in distinguishing inflamed biopsies from their control counterparts (AUC of 93.3% and 91.1% in the training, 95.0% and 96.0% in the test, and 89.5% and 78.3% in the external validation datasets, respectively). Furthermore, the differentially expressed MUC4 (PB.1238.363), MUC5AC (PB.2811.15), MUC16 (ENST00000397910.8) and MUC1 (ENST00000462317.5, ENST00000620103.4) RNA isoforms frequently occurred throughout the different panels highlighting their role in IBD pathogenesis.</p><p><strong>Conclusion: </strong>We unveiled region-specific mucin RNA isoform panels capturing the heterogeneity of the IBD patient population and showing great potential to indicate barrier function in IBD patients.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142335258","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}