RT Journal Article SR Electronic T1 Lactobacillus acidophilus disrupts collaborative multispecies bile acid metabolism JF bioRxiv FD Cold Spring Harbor Laboratory SP 296020 DO 10.1101/296020 A1 Sydney Dautel A1 Nymul Khan A1 Kristoffer R. Brandvold A1 Colin J. Brislawn A1 Janine Hutchison A1 Karl K. Weitz A1 Heino M. Heyman A1 Hyun-Seob Song A1 Zehra Esra Ilhan A1 Eric A. Hill A1 Joshua R. Hansen A1 Xueyun Zheng A1 Erin S. Baker A1 John R. Cort A1 Young-Mo Kim A1 Nancy G. Isern A1 John K. DiBaise A1 Rosa Krajmalnik-Brown A1 Janet K. Jansson A1 Aaron T. Wright A1 Thomas O. Metz A1 Hans C. Bernstein YR 2018 UL http://biorxiv.org/content/early/2018/04/11/296020.2.abstract AB Bile 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, and Blautia 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.