Metagenomic analysis of bile salt biotransformation in the human gut microbiome

Abstract

Background In the biochemical milieu of human colon, bile acids act as signaling mediators between the host and its gut microbiota. Biotransformation of primary to secondary bile acids have been known to be involved in the immune regulation of human physiology. Several 16S amplicon-based studies with inflammatory bowel disease (IBD) subjects were found to have an association with the level of fecal bile acids. However, a detailed investigation of all the bile salt biotransformation genes in the gut microbiome of healthy and IBD subjects has not been performed. Results Here, we report a comprehensive analysis of the bile salt biotransformation genes and their distribution at the phyla level. Based on the analysis of shotgun metagenomes, we found that the IBD subjects harbored a significantly lower abundance of these genes compared to the healthy controls. Majority of these genes originated from Firmicutes in comparison to other phyla. From metabolomics data, we found that the IBD subjects were measured with a significantly low level of secondary bile acids and high levels of primary bile acids compared to that of the healthy controls. Conclusions Our bioinformatics-driven approach of identifying bile salt biotransformation genes predicts the bile salt biotransformation potential in the gut microbiota of IBD subjects. The functional level of dysbiosis likely contributes to the variation in the bile acid pool. This study sets the stage to envisage potential solutions to modulate the gut microbiome with the objective to restore the bile acid pool in the gut. Electronic supplementary material The online version of this article (10.1186/s12864-019-5899-3) contains supplementary material, which is available to authorized users.

Dysbiosis in metabolic genes of the gut microbiomes of patients with an ileo-anal pouch resembles that observed in Crohn’s Disease

“…A reduction in secondary bile acids genes in patients with CD or UC [25, 57] as well as a reduction in DCA and LCA metabolites in highly-dysbiotic patients with UC and CD, was previously described [13], supporting our current study. The key species encoding bai clusters in our metagenomes are concordant with those identified in metagenomes of a healthy population [56].…”

Fecal Bacteria as Biomarkers for Predicting Food Intake in Healthy Adults

“…In addition, microbes in the oral cavity, gastrointestinal tract, and pancreatic tissue differed in patients with pancreatic cancer compared with healthy controls ( 46 ). Also, Das et al ( 47 ) linked microbial metabolites to inflammatory bowel disease and Turnbaugh et al ( 48 ) revealed changes in fecal microbial structure, gene expression, and subsequent metabolic pathways due to dietary changes. Although these studies are not without limitations, they reveal promise in the utility of fecal samples to fill the need for noninvasive, inexpensive, and specific markers of dietary intake and health status ( 49 ).…”

Colon Carcinogenesis: The Interplay Between Diet and Gut Microbiota

“…Increase the Firmicutes to Bacteroidetes ratio, which was linked to obesity; promote the enrichment of mucin-degrading Actinobacteria; decrease beneficial gut microbiota such as Bifidobacterium, Lactobacillus, and Akkermansia (Murphy et al, 2010;Islam et al, 2011;Kim et al, 2012;Lecomte et al, 2015;Taira et al, 2015;Cao et al, 2017;He et al, 2018) Mediate the conversion of bile acids into secondary bile acids; dysbiosis is associated with impaired bile acid metabolism and inflammatory bowel diseases (Duboc et al, 2013;Zou et al, 2018;Das et al, 2019) chromosomal damage to facilitate malignant transformation. Interestingly, the production of genotoxin is not restricted to only the typically pathogenic bacteria but also commensal bacteria.…”

“…A dysbiosis characterized by a decrease in the ratio between Faecalibacterium prausntizii and E. coli was associated with an impaired bile acid metabolism in patients with inflammatory bowel diseases (IBD), as reflected by their higher level of fecal bile acids ( Duboc et al., 2013 ). In a recent metagenomics analysis, a lower abundance of genes of bile-metabolizing Firmicutes was detected in the gut microbiota of IBD individuals, again linking microbial dysbiosis with the disease state ( Das et al., 2019 ). Of note, the interaction between bile acids and gut microbiota is bidirectional as bile acids serve as antimicrobial agents that help shape the gut microbiome structure ( Ridlon et al., 2016 ).…”