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Elife. 2018 Jul 17;7. pii: e37182. doi: 10.7554/eLife.37182.

A selective gut bacterial bile salt hydrolase alters host metabolism.

Author information

1
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, United States.
2
Department of Pathology, Massachusetts Host-Microbiome Center, Brigham and Women's Hospital, Boston, United States.
3
Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Boston, United States.

Abstract

The human gut microbiota impacts host metabolism and has been implicated in the pathophysiology of obesity and metabolic syndromes. However, defining the roles of specific microbial activities and metabolites on host phenotypes has proven challenging due to the complexity of the microbiome-host ecosystem. Here, we identify strains from the abundant gut bacterial phylum Bacteroidetes that display selective bile salt hydrolase (BSH) activity. Using isogenic strains of wild-type and BSH-deleted Bacteroides thetaiotaomicron, we selectively modulated the levels of the bile acid tauro-β-muricholic acid in monocolonized gnotobiotic mice. B. thetaiotaomicron BSH mutant-colonized mice displayed altered metabolism, including reduced weight gain and respiratory exchange ratios, as well as transcriptional changes in metabolic, circadian rhythm, and immune pathways in the gut and liver. Our results demonstrate that metabolites generated by a single microbial gene and enzymatic activity can profoundly alter host metabolism and gene expression at local and organism-level scales.

KEYWORDS:

bacteroides thetaiotaomicron; bile salt hydrolase; biochemistry; chemical biology; human microbiome; infectious disease; metabolism; microbiology; mouse

Conflict of interest statement

LY, SN, AA, ND, AM, AB, LB No competing interests declared, SS is currently affiliated with Indigo Agriculture, but the research was conducted when she was a Research Associate at Harvard Medical School. The author has no other competing interests to declare, AD is a consultant for Kintai Therapeutics

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