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
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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