Taxonomic profiling and populational patterns of bacterial bile salt hydrolase (BSH) genes based on worldwide human gut microbiome

Abstract

BackgroundBile salt hydrolase plays an important role in bile acid-mediated signaling pathways, which regulate lipid absorption, glucose metabolism, and energy homeostasis. Several reports suggest that changes in the composition of bile acids are found in many diseases caused by dysbacteriosis.ResultsHere, we present the taxonomic identification of bile salt hydrolase (BSH) in human microbiota and elucidate the abundance and activity differences of various bacterial BSH among 11 different populations from six continents. For the first time, we revealed that bile salt hydrolase protein sequences (BSHs) are distributed in 591 intestinal bacterial strains within 117 genera in human microbiota, and 27.52% of these bacterial strains containing BSH paralogs. Significant variations are observed in BSH distribution patterns among different populations. Based on phylogenetic analysis, we reclassified these BSHs into eight phylotypes and investigated the abundance patterns of these phylotypes among different populations. From the inspection of enzyme activity among different BSH phylotypes, BSH-T3 showed the highest enzyme activity and is only found in Lactobaclillus. The phylotypes of BSH-T5 and BSH-T6 mainly from Bacteroides with high percentage of paralogs exhibit different enzyme activity and deconjugation activity. Furthermore, we found that there were significant differences between healthy individuals and patients with atherosclerosis and diabetes in some phylotypes of BSHs though the correlations were pleiotropic.ConclusionThis study revealed the taxonomic and abundance profiling of BSH in human gut microbiome and provided a phylogenetic-based system to assess BSHs activity by classifying the target sequence into specific phylotype. Furthermore, the present work disclosed the variation patterns of BSHs among different populations of geographical regions and health/disease cohorts, which is essential to understand the role of BSH in the development and progression of related diseases.Electronic supplementary materialThe online version of this article (10.1186/s40168-019-0628-3) contains supplementary material, which is available to authorized users.

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

“…25,26 In case of BSHs, previous studies have classified BSHs into three, four, or eight clusters based on phylogenetic analysis; however, these analyses were based on <400 protein sequences. [15][16][17] Song et al grouped BSHs into eight clusters using phylogenetic analysis, but the classification separated several BSHs with high sequence identity into different clusters, 17 which led to overclassification. In this study, we collected the experimentally characterized enzymes from previous studies and further extended the amount to 5,790 protein sequences.…”

“…Two enzymes in this cluster (UniProt ID: R6GBZ3 and A0A380KNN4) have shown 8-fold differences in the specific activity compared to that of GCA even though they share only 60% identity. 17 On the other hand, enzymes from Cluster 2 (R6GBZ3) and Cluster 7 (E2YQS1) have shown specific activity similar to that of GCA even though they share only 20% identity. 17 The experimentally characterized enzymes from the 7 clusters can hydrolyze both tauro-and glyco-conjugated bile salts.…”

“…17 On the other hand, enzymes from Cluster 2 (R6GBZ3) and Cluster 7 (E2YQS1) have shown specific activity similar to that of GCA even though they share only 20% identity. 17 The experimentally characterized enzymes from the 7 clusters can hydrolyze both tauro-and glyco-conjugated bile salts. BSH is closely related to penicillin V amidase, and the substrate specificities of the two enzymes cannot be distinguished on the basis of protein sequence or phylogenetic tree analysis.…”

“…We reviewed the experimentally characterized BSHs in previously published papers. [15][16][17] A total of 44 enzymes that had been previously characterized were selected (Supplementary Table S1). These proteins were used as query sequences to search the UniProt protein database.…”

Gut microbes from the phylogenetically diverse genusEubacteriumand their various contributions to gut health

“…along with other genera such as Roseburia and Clostridium constitute a major reservoir of BSHs in the gut. 172 Deconjugation increases the pK a of BAs to ~5, thereby making them less soluble which in turn leads to inefficient absorption and replenishment of the lost BA by de novo synthesis from cholesterol. 173 Additionally, BSH activity can disrupt micelle formation and absorption, resulting in a significant reduction of cholesterol levels.…”