Integrative analysis of colonic biopsies from inflammatory bowel disease patients identifies an interaction between microbial bile-acid inducible gene abundance and human Angiopoietin-like 4 gene expression.

Abstract

BACKGROUND AND AIMS\nMicrobial derived-bile acids can modulate host gene expression, and their fecal abundance is decreased in active inflammatory bowel disease (IBD). We analyzed the impact of endoscopic inflammation on microbial genes involved in bile acid biotransformation, and their interaction with host transcriptome in the intestinal mucosa of IBD patients.\n\n\nMETHODS\nEndoscopic mucosal biopsies were collected from non-inflamed and inflamed terminal ileum, ascending and sigmoid colon of IBD patients. Prediction of imputed metagenome functional content from 16S rRNA profile and real-time qPCR were utilized to assess microbial bile acid biotransformation gene abundance, and RNA-seq was used for host transcriptome analysis. Linear regression and partial Spearman correlation accounting for age, sex and IBD type were used to assess the association between microbial genes, inflammation and host transcriptomics in each biopsy location. A Bayesian network (BN) analysis was fitted to infer the direction of interactions between IBD traits, microbial and host genes.\n\n\nRESULTS\nInferred microbial gene pathway involved in secondary bile acid biosynthesis (ko00121 pathway) was depleted in inflamed terminal ileum of IBD patients compared to non-inflamed tissue. In non-inflamed sigmoid colon, the relative abundance of bile acid-inducible (baiCD) microbial genes was positively correlated with the host Angiopoietin-like 4 (Angptl4) gene expression. The BN analysis suggests that the microbial baiCD gene abundance could affect Angptl4 expression, and this interaction appears to be lost in the presence of inflammation.\n\n\nCONCLUSIONS\nEndoscopic inflammation affects the abundance of crucial microbial bile acid-metabolizing genes and their interaction with Angptl4 in intestinal mucosa of IBD patients.