A selective gut bacterial bile salt hydrolase alters host metabolism
- Harvard Medical School, United States
- Brigham and Women's Hospital, 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-b-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.
Data availability
RNA-Seq data are deposited in the Gene Expression Omnibus (GEO) database (accession GSE112571, Go to https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE112571).All other data generated or analyzed during this study are included in the manuscript and supporting files.
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A selective gut bacterial bile salt hydrolase alters host metabolismPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE112571).
Article and author information
Author details
Funding
The Center for Microbiome Informatics and Therapeutics at MIT (Innovation Award)
- Arijit A Adhikari
- A Sloan Devlin
The Harvard Digestive Diseases Center (NIH grant P30DK034854)
- Lina Yao
- Sarah Craven Seaton
- Sula Ndousse-Fetter
- Arijit A Adhikari
- Nicholas DiBenedetto
- Lynn Bry
- A Sloan Devlin
Karin Grunebaum Cancer Research Foundation (Junior Faculty Award)
- A Sloan Devlin
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All experiments involving mice were performed using IACUC approved protocols (Protocol # 2017N000053) at the Brigham and Women's Hospital Center for Comparative Medicine.
Copyright
© 2018, Yao et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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A selective gut bacterial bile salt hydrolase alters host metabolism
eLife 7:e37182.
https://doi.org/10.7554/eLife.37182
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