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

Abstract

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 (n = 1,605) and healthy controls (n = 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.

Diet-Related Alterations of Gut Bile Salt Hydrolases Determined Using a Metagenomic Analysis of the Human Microbiome

“…The protein sequence similarity network (SSN) of the gut BSHs was further generated with a criterion of >40% sequence identity, which separated the gut BSHs into seven clusters ( Figure 2 a and Supplementary Figure S1 ). The classification was in accordance with that of our previous study, and we named the clusters similarly to facilitate understanding [ 16 ]. The proteins from Clusters 1 and 3 were predominantly from Bacteroidetes, consisting of 136 and 71 proteins, respectively.…”

“…Our previous study suggested that the abundance of BSHs from different clusters showed distinct relationships with human diseases [ 16 ]. In this study, we mapped the gut BSH sequences in each cluster to the datasets of different diets to evaluate the relationship.…”

“…BSHs in the gut are from 12 phyla but mainly belong to the two dominant gut phyla Bacteroidetes and Firmicutes [ 11 ]. The BSHs from the bacteria of these two phyla are considerably different in sequence; the proteins from Bacteroidetes contain N-terminal signal peptides, while those from Firmicutes do not harbor these peptides [ 16 ]. This sequence difference motivated us to examine how the community structure of BSH microbes is affected by diet.…”

“…The effect of BSHs on human health is currently unclear. Recently, we demonstrated that gut BSH abundance is significantly related to human diseases, including obesity and T2D as well as cardiovascular, liver, gastrointestinal, and neurological diseases [ 16 ]. Among these diseases, the risk of obesity, T2D, and cardiovascular diseases is closely linked to dietary patterns [ 17 ].…”

An acidic-groups detection method and its application to analysis of Chinese humic acid samples

“…As the acid-insoluble fractions of humic substances, Humic acid is partially soluble in water and form micelle-like structures in neutral to acidic conditions [2]. Humic acid is polymer compound rich in active groups such as phenolic-hydroxyl, carboxyl, sulfhydryl, and carbonyl [3,4] and is widely used in agriculture, ceramics, oil extraction, and environmental protection as an organic fertilizer, binder, mining aid, water purifier, and heavy-metal remover [5][6][7][8][9][10][11]. Humic acid is mainly found naturally in peat, lignite, and weathered coal in nature [12,13], which composition can vary according to geographical origin, age, climate and biological conditions, making the precise characterization of these substances difficult [14,15].…”