Taxonomic identification of bile salt hydrolase-encoding lactobacilli: Modulation of the enterohepatic bile acid profile

Bile salt hydrolases (BSHs) are enzymes that are essential for the enterohepatic metabolism of bile acids (BAs). BSHs catalyze the production of unconjugated BAs and regulate the homeostasis of BA pool. This study identified Lactobacillus as a crucial BSH-encoding genus, and 16 main species were obtained using metagenomic data from publicly available human gut microbiome databases. Then, the 16 species of lactobacilli were classified into four typical categories by BSH phylotypes, including five species encoding BSH-T0, six species encoding BSH-T2, four species encoding BSH-T3, and Ligilactobacillus salivarius encoding both BSH-T0 and BSH-T3. The lactobacilli with the highest in vitro deconjugation activities against seven conjugated BAs were the BSH-T3-encoding strains. Furthermore, in vivo studies in mice administered four representative lactobacilli strains encoding different BSH phylotypes showed that treatment with BSH-T3-encoding Limosilactobacillus reuteri altered the structure of the gut microbiome and metabolome and significantly increased the levels of unconjugated BAs and total BA excretion. Our findings facilitated the taxonomic identification of crucial BSH-encoding lactobacilli in human gut microbiota and shed light on their contributions toward modulation of the enterohepatic circulation of BAs, which will contribute to future therapeutic applications of BSH-encoding probiotics to improve human health.