Metagenomic analysis of the human microbiome reveals the association between the abundance of gut bile salt hydrolases and host health

Apr 25, 2020Gut microbes

Gut bacteria with bile salt enzymes linked to human health

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Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

A total of 5,790 bile salt hydrolase (BSH) homologs were analyzed for their association with various human diseases.

BSH homologs were classified into seven clusters based on sequence similarity.
Different clusters of BSHs occupied diverse ecological niches within the human microbiome.
Clusters containing signal peptides were found to be relatively abundant in the gut.
Analysis revealed significant associations between BSH gene abundance and 10 human diseases, including obesity and type 2 diabetes.
Findings were validated in separate cohorts with inflammatory bowel diseases and colorectal cancer.

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Bile acid metabolism by the gut microbiome exerts both beneficial and harmful effects on host health. Microbial bile salt hydrolases (BSHs), which initiate bile acid metabolism, exhibit both positive and negative effects on host physiology. In this study, 5,790 BSH homologs were collected and classified into seven clusters based on a sequence similarity network. Next, the abundance and distribution of BSH in 380 metagenomes from healthy participants were analyzed. It was observed that different clusters occupied diverse ecological niches in the human microbiome and that the clusters with signal peptides were relatively abundant in the gut. Then, the association between BSH clusters and 12 human diseases was analyzed by comparing the abundances of BSH genes in patients (= 1,605) and healthy controls (= 1,540). The analysis identified a significant association between BSH gene abundance and 10 human diseases, including gastrointestinal diseases, obesity, type 2 diabetes, liver diseases, cardiovascular diseases, and neurological diseases. The associations were further validated by separate cohorts with inflammatory bowel diseases and colorectal cancer. These large-scale studies of enzyme sequences combined with metagenomic data provide a reproducible assessment of the association between gut BSHs and human diseases. This information can contribute to future diagnostic and therapeutic applications of BSH-active bacteria for improving human health. n n

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Metagenomic analysis of the human microbiome reveals the association between the abundance of gut bile salt hydrolases and host health

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