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
Autor: | Gideon M. Hirschfield, Andrew D Beggs, Julian R.F. Walters, Tariq Iqbal, Richard D. Horniblow, Nicholas J. Loman, David R. Withers, Subrata Ghosh, Chris Tselepis, Georgios V. Gkoutos, Animesh Acharjee, Willem van Schaik, Mohammed Nabil Quraishi, Amanda E. Rossiter |
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Rok vydání: | 2020 |
Předmět: |
Male
LIVER endocrine system diseases colitis Gut flora Gastroenterology Inflammatory bowel disease Transcriptome ACTIVATION RNA Ribosomal 16S Homeostasis TH17 Intestinal Mucosa Bile acid biology digestive oral and skin physiology Interleukin-17 General Medicine dysbiosis bioinformatics Middle Aged Ulcerative colitis Up-Regulation Autoimmune liver disease Female Life Sciences & Biomedicine Signal Transduction Adult medicine.medical_specialty medicine.drug_class Colon Cholangitis Sclerosing digestive system Primary sclerosing cholangitis Immunophenotyping Bile Acids and Salts Internal medicine medicine Humans Colitis GENOME-WIDE ASSOCIATION AcademicSubjects/MED00260 Science & Technology Gastroenterology & Hepatology business.industry Sequence Analysis RNA Immunity Computational Biology 1103 Clinical Sciences Original Articles medicine.disease biology.organism_classification RISK LOCI digestive system diseases Eccojc/1000 Gastrointestinal Microbiome Case-Control Studies CELLS Th17 Cells Colitis Ulcerative business Dysbiosis |
Zdroj: | Journal of Crohn's & Colitis |
ISSN: | 1876-4479 |
Popis: | 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 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. |
Databáze: | OpenAIRE |
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