Lactobacillus acidophilusdisrupts collaborative multispecies bile acid metabolism

ABSTRACTBile acids are metabolic links between hosts and their gut microbiomes, yet little is known about the roles they play in microbe-to-microbe interactions. Here we present a study designed to investigate the effect that a common probiotic,Lactobacillus acidophilus, has on microbial interactions that lead to formation of secondary bile acids. A model microbial consortium was built from three human gut isolates,Clostridium scindens, Collinsella aerofaciens,andBlautia obeum, and cultured under different bile acid and probiotic treatments. A multi-omics platform that included mass spectrometry-based metabolomics and activity-based proteomic probes was used to produce two major results. The first, was that an uncommon secondary bile acid – ursocholate – was produced by a multi-species chemical synthesis pathway. This result highlights a new microbe-to-microbe interaction mediated by bile acids. The second finding was that the probiotic strain,L. acidophilus,quenched the observed interactions and effectively halted consortial synthesis of ursocholate. Little is known about the role that ursocholate plays in human health and development. However, we did discover that a decrease in ursocholate abundance corresponded with successful weight loss in patients after gastric bypass surgery versus those who did not lose weight after surgery. Hence, this study uncovered basic knowledge that may aid future designs of custom probiotic therapies to combat obesity.