Project description:Patients with both primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) run a 10-fold increased risk of developing colorectal carcinoma (CRC) compared to patients with IBD only. It is unknown which mucosal defects are causing this increased risk. The aim of this study was to investigate which molecular changes give rise to CRC in patients with PSC-IBD, and whether changes occur already in non-dysplastic mucosa.
Project description:Mucosal-luminal interface (MLI) samples were collected from a cohort of children with new-onset IBD and microbial cells were harvested and processed for metaproteomic analysis. Deep metaproteomics data analysis was then performed for better understanding the MLI microbiota functions in the development of pediatric IBD.
Project description:Approximately 80% of patients with Primary Sclerosing Cholangitis (PSC) also have an underlying Inflammatory Bowel Disease (IBD). Notably, PSC-IBD presents a unique phenotype compared to Ulcerative Colitis or Crohn’s Disease alone , which may increase the risk of colitis-associated neoplasia. This case-control study comprises a cohort of 15 patients in the PSC-IBD group, 30 patients in the IBD-alone group, and 19 patients in the control group. Through the analysis of patient serum and colon tissue proteomics, colon gene expression, fecal gut microbiota, and in vitro data with human monocytes, we identified a specific interplay between systemic circulation and gut microbiota dysbiosis that may predispose PSC-IBD patients to neoplasia development. Our study revealed that PSC-IBD patients show a shift in gut microbiota towards an increase in Intestinibacter, a bacterium known to exacerbate IBD conditions.Interestingly, when comparing the PSC-IBD group to the IBD-alone group, we observed elevated miR-21 expression levels in fasting serum and stool samples. Finally, we partially reproduce the inflammatory PSC-IBD profile using miR-21 and bile acid GCDCA stimulus in human-derived monocytes. Our findings suggest that circulating miR-21, along with bile acid GCDCA, tissue macrophage recruitment, and distinct microbiota profiles, may contribute to the unique phenotype of IBD in PSC patients.
Project description:We used microarrays to identify mucosal gene signatures predictive of response to infliximab (IFX) in patients with inflammatory bowel disease (IBD) and to gain more insight into the pathogenesis of IBD. Keywords: drug response and treatment effect Mucosal biopsies were obtained at endoscopy in actively inflamed mucosa from 61 IBD patients (24 ulcerative colitis (UC), 19 Crohnâs colitis (CDc) and 18 Crohnâs ileitis (CDi)), refractory to corticosteroids and/or immunosuppression, before and 4-6 weeks after (except for 1 CDc patient) their first infliximab infusion and in normal mucosa from 12 control patients (6 colon and 6 ileum). The patients were classified for response to infliximab based on endoscopic and histologic findings at 4-6 weeks after first infliximab treatment. Total RNA was isolated from intestinal mucosal biopsies, labelled and hybridized to Affymetrix Human Genome U133 Plus 2.0 Arrays.
