Mucosal Single-Cell Profiling of Crohn's-Like Disease of the Pouch Reveals Unique Pathogenesis and Therapeutic Targets
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE246987 | GEO | 2024/08/02
REPOSITORIES: GEO
Similar Datasets
Project description:Pouchitis is a common complication for ulcerative colitis (UC) patients with ileal pouch-anal anastomosis (IPAA) surgery. Similarly to IBD, both innate host factors such as genetics, and environmental stimuli including the tissue-associated microbiome have been implicated in the pathogenesis. In this study, we make use of the IPAA model of inflammatory bowel disease (IBD) to carry out a study associating mucosal host gene expression with the microbiome and corresponding clinical outcomes.
2015-01-27 | GSE65270 | GEO
Project description:A total proctocolectomy with ileal pouch-anal anastomosis (IPAA) is considered the surgery of choice for definitive management of familial adenomatous polyposis (FAP) and selected patients with ulcerative colitis (UC). However, this surgical treatment often associates with a long-term complication, pouchitis, which occurs mostly in UC patients. To better define the molecular background of pouchitis, the microarray-based survey was performed using pouch mucosal samples collected from 28 and 8 patients operated for UC and FAP, respectively. A number of 4771 genes was significantly differentiating uninflamed from inflamed mucosal samples, and their functional features were represented mostly by alerted metabolic and cell proliferation pathways. In contrast, functional analyses of aberrantly expressed probe sets between UC and FAP samples, irrespectively of mucosal inflammation status, revealed multiple pathways and terms which were linked to changes in immune response. Noteworthy, the comparison of uninflamed UC and FAP samples distinguished a set of 26 altered mRNAs including inflammation-related transcript encoding a Charcot-Leyden crystal (CLC) protein. The most discrete changes in gene expression profiles differentiating uninflamed UC and FAP mucosal samples were attributed to a Gene Ontology category innate immune response. Our study confirmed alterations of the immune responses as dominant in UC pouchitis which were earlier found in the studies using analyses of singular molecular elements. This observation may be important when managing IPAA patients. Each sample represents three biopsies taken from single patient, from the same areas of the lower part of the pouch mucosa (above the rectal cuff) during endoscopic examination. 28 patients underwent surgery for UC and 8 patients for FAP.
2014-05-01 | E-GEOD-50788 | biostudies-arrayexpress
Project description:Restorative proctocolectomy with ileal pouch-anal anastomosis is a surgical procedure in patients with ulcerative colitis refractory to medical therapies. Pouchitis, the most common complication, is inflammation of the pouch of unknown etiology. To define how the intestinal immune system is distinctly organized in response to inflammation and to develop mechanistic hypotheses of pouchitis, we analyzed tissues from patients with and without pouchitis and from patients with ulcerative colitis using single-cell RNA sequencing. We examined pouch lamina propria CD45+ hematopoietic cells from intestinal tissues of ulcerative colitis patients with (n=15) and without an ileal pouch-anal anastomosis (n=11). Further in silico meta-analysis was performed to generate transcriptional interaction networks and identify drug targets for patients with inflamed pouches. We identified a population of IL1B+ antimicrobial macrophages and FOXP3+/BATF+ T cells that are expanded in inflamed tissues, which we further validated in other single cell RNA-seq datasets from IBD patients. Cell type specific markers obtained from single-cell RNA-sequencing was used to infer representation from bulk RNA sequencing datasets, which further implicated antimicrobial macrophages expressing IL1B with S100A8/A9 calprotectin as being associated with inflammation, and Bacteroidiales and Clostridiales bacterial taxa. We found that non-responsiveness to anti-integrin biologic therapies in ulcerative colitis patients was associated with the signature of this antimicrobial macrophage population in a subset of patients. This study identified conserved and distinct features of intestinal inflammation between parts of the small and large intestine undergoing similar inflammation conditions. Specifically, we relate inflammation of the pouch, a surgically constructed organ, to other inflammatory contexts throughout the gastrointestinal tract.
2020-12-01 | GSE162335 | GEO
Project description:Total proctocolectomy with ileal pouch anal anastomosis (IPAA) is the standard treatment for patients with severe treatment resistant ulcerative colitis (UC). Despite significant improvements in patient outcomes, up to 50% of patients will develop inflammation of the pouch (pouchitis) within 1-2 years following surgery. The pathogenesis of pouchitis is not well understood. Functionalization of UC pouches is associated with histological changes, whether these reflect changes in cellular identity and metaplasia remains unclear. To address this question, we generated cellular atlases of single-cell transcriptomes and accessible chromatin to assess the cellular composition, transcriptomic and epigenetic profiles in UC pouches.
2023-11-15 | GSE242086 | GEO
Project description:Total proctocolectomy with ileal pouch anal anastomosis (IPAA) is the standard treatment for patients with severe treatment resistant ulcerative colitis (UC). Despite significant improvements in patient outcomes, up to 50% of patients will develop inflammation of the pouch (pouchitis) within 1-2 years following surgery. The pathogenesis of pouchitis is not well understood. Functionalization of UC pouches is associated with histological changes, whether these reflect changes in cellular identity and metaplasia remains unclear. To address this question, we generated cellular atlases of single-cell transcriptomes and accessible chromatin to assess the cellular composition, transcriptomic and epigenetic profiles in UC pouches.
2023-11-15 | GSE242085 | GEO
Project description:A total proctocolectomy with ileal pouch-anal anastomosis (IPAA) is considered the surgery of choice for definitive management of familial adenomatous polyposis (FAP) and selected patients with ulcerative colitis (UC). However, this surgical treatment often associates with a long-term complication, pouchitis, which occurs mostly in UC patients. To better define the molecular background of pouchitis, the microarray-based survey was performed using pouch mucosal samples collected from 28 and 8 patients operated for UC and FAP, respectively. A number of 4771 genes was significantly differentiating uninflamed from inflamed mucosal samples, and their functional features were represented mostly by alerted metabolic and cell proliferation pathways. In contrast, functional analyses of aberrantly expressed probe sets between UC and FAP samples, irrespectively of mucosal inflammation status, revealed multiple pathways and terms which were linked to changes in immune response. Noteworthy, the comparison of uninflamed UC and FAP samples distinguished a set of 26 altered mRNAs including inflammation-related transcript encoding a Charcot-Leyden crystal (CLC) protein. The most discrete changes in gene expression profiles differentiating uninflamed UC and FAP mucosal samples were attributed to a Gene Ontology category innate immune response. Our study confirmed alterations of the immune responses as dominant in UC pouchitis which were earlier found in the studies using analyses of singular molecular elements. This observation may be important when managing IPAA patients.
2014-05-01 | GSE50788 | GEO
Project description:Pouchitis is a common complication for ulcerative colitis (UC) patients with ileal pouch-anal anastomosis (IPAA) surgery. Similarly to IBD, both innate host factors such as genetics, and environmental stimuli including the tissue-associated microbiome have been implicated in the pathogenesis. In this study, we make use of the IPAA model of inflammatory bowel disease (IBD) to carry out a study associating mucosal host gene expression with the microbiome and corresponding clinical outcomes. In order to determine how host gene expression might influence, or be influenced by the tissue associated microbiome, we analyzed 205 IPAA patients with biopsies collected from the pouch and afferent limb for host transcriptomics and 16S rDNA gene sequencing. Metadata included antibiotic use, inflammation score, and clinical classification. To achieve power for a genome-wide microbiome-transcriptome association study, we used principal component analysis to reduce OTUs and host transcripts to eigengenes and eigenclades explaining 50% of observed variance. These were subsequently tested for significant covariation with one another and/or outcome using multivariate linear modeling.
2015-01-27 | E-GEOD-65270 | biostudies-arrayexpress
Project description:The goal of the study was to compare the influence of Ileal pouch-anal anastomosis (IPAA) surgical treatment on patients with ulcerative colitis (UC) vs those with familial adenomatous polyposis (FAP). Stool samples were obtained at the time of clinic visit, immediately frozen and stored at -80oC until the assay. There were no exclusion criteria.
2014-09-10 | ST000277 | MetabolomicsWorkbench
Project description:Little is known about the factors that predispose patients to complications after an ileal pouch-anal anastomosis procedure (IPAA). Our goal is to establish a registry that prospectively captures pre- and post-surgical data from participants. Retrospective studies concerning IPAA outcomes and will be conducted using these data.
| 2081764 | ecrin-mdr-crc
Project description:Gut Microbiome in Inflammatory Complications Following Ileal Pouch - Anal Anastomosis
| PRJNA217699 | ENA