A pilot integrative analysis of colonic gene expression, gut microbiota, and immune infiltration in primary sclerosing cholangitis-inflammatory bowel disease: association of disease with bile acid pathways.
Quraishi, Mohammed Nabil Acharjee, Animesh Beggs, Andrew D Horniblow, Richard Tselepis, Chris Gkoutos, Georgios Rossiter, A E Loman, Nicholas van Schaik, Willem
Quraishi, Mohammed Nabil
Acharjee, Animesh
Beggs, Andrew D
Horniblow, Richard
Tselepis, Chris
Gkoutos, Georgios
Rossiter, A E
Loman, Nicholas
van Schaik, Willem
Abstract
Background: Although a majority of patients with PSC have colitis [PSC-IBD; primary sclerosing cholangitis-inflammatory bowel disease], this is phenotypically different from ulcerative colitis [UC]. We sought to define further the pathophysiological differences between PSC-IBD and UC, by applying a comparative and integrative approach to colonic gene expression, gut microbiota and immune infiltration data.
Methods: Colonic biopsies were collected from patients with PSC-IBD [n = 10], UC [n = 10], and healthy controls [HC; n = 10]. Shotgun RNA-sequencing for differentially expressed colonic mucosal genes [DEGs], 16S rRNA analysis for microbial profiling, and immunophenotyping were performed followed by multi-omic integration.
Results: The colonic transcriptome differed significantly between groups [p = 0.01]. Colonic transcriptomes from HC were different from both UC [1343 DEGs] and PSC-IBD [4312 DEGs]. Of these genes, only 939 had shared differential gene expression in both UC and PSC-IBD compared with HC. Imputed pathways were predominantly associated with upregulation of immune response and microbial defense in both disease cohorts compared with HC. There were 1692 DEGs between PSC-IBD and UC. Bile acid signalling pathways were upregulated in PSC-IBD compared with UC [p = 0.02]. Microbiota profiles were different between the three groups [p = 0.01]; with inferred function in PSC-IBD also being consistent with dysregulation of bile acid metabolism. Th17 cells and IL17-producing CD4 cells were increased in both PSC-IBD and UC when compared with HC [p < 0.05]. Multi-omic integration revealed networks involved in bile acid homeostasis and cancer regulation in PSC-IBD.
Conclusions: Colonic transcriptomic and microbiota analysis in PSC-IBD point toward dysregulation of colonic bile acid homeostasis compared with UC. This highlights important mechanisms and suggests the possibility of novel approaches in treating PSC-IBD.
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Date
2020-07-30
Type
Article
Subject
Oncology. Pathology., Genetics, Microbiology. Immunology
Citation
Quraishi MN, Acharjee A, Beggs AD, Horniblow R, Tselepis C, Gkoutos G, Ghosh S, Rossiter AE, Loman N, van Schaik W, Withers D, Walters JRF, Hirschfield GM, Iqbal TH. A Pilot Integrative Analysis of Colonic Gene Expression, Gut Microbiota, and Immune Infiltration in Primary Sclerosing Cholangitis-Inflammatory Bowel Disease: Association of Disease With Bile Acid Pathways. J Crohns Colitis. 2020 Jul 30;14(7):935-947. doi: 10.1093/ecco-jcc/jjaa021
Journal / Source Title
Journal of Crohn's & Colitis
DOI
10.1093/ecco-jcc/jjaa021
PMID
32016358
Publisher
Oxford University Press
Publisher’s URL
https://academic.oup.com/ecco-jcc