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, Gkoutus, Georgios, Ghosh, Subrata, Rossiter, Amanda, Loman, Nicholas, van Schaik, Willem, Withers, David, Walters, Julian R F, Hirschfield, Gideon M and Iqbal, Tariq H (2020) 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. Journal of Crohn's & colitis. ISSN 1876-4479.

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Official URL: https://academic.oup.com/ecco-jcc/advance-article/...

Abstract

BACKGROUND

Although majority of patients with PSC have colitis (PSC-IBD) this is phenotypically different from UC. We sought to define further the pathophysiologic differences in PSC-IBD and UC, by applying a comparative and integrative approach in this pilot study.

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 to HC. Imputed pathways were predominantly associated with upregulation of immune response and microbial defence in both disease cohorts compared to HC. There were 1692 DEGs between PSC-IBD and UC. Bile acid signalling pathways were upregulated in PSC-IBD compared to 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 to 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 points toward dysregulation of colonic bile acid homeostasis compared to UC. This highlights important mechanisms and suggests the possibility of novel approaches in treating PSC-IBD.

Item Type: Article
Subjects: QW Microbiology. Immunology
WI Digestive system. Gastroenterology
Divisions: Clinical Support > Infection Control
Planned IP Care > Gastroentrology
Related URLs:
Depositing User: Mr Muneeb Liaquat
Date Deposited: 07 Feb 2020 13:59
Last Modified: 07 Feb 2020 13:59
URI: http://www.repository.uhblibrary.co.uk/id/eprint/2836

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