Journal
CELL
Volume 177, Issue 5, Pages 1217-+Publisher
CELL PRESS
DOI: 10.1016/j.cell.2019.03.036
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Funding
- Yale University School of Medicine
- Kingsley Award in Biomedical Research
- Leona M. and Harry B. Helmsley Charitable Trust [3083]
- Richard and Susan Smith Family Foundation
- Rainin Foundation
- Global Probiotics Council
- National Institutes of Health [K22 AI123477, R21 AI137935, 1DP2-CA186575]
- TATA Sons Limited, India [YTP-2016-002]
- Juvenile Diabetes Research Foundation [2-SRA-2018-549-B]
- Camille and Henry Dreyfus Foundation [TC-17-011]
- Damon Runyon Cancer Research Foundation [DRR-39-16]
- Burroughs Wellcome Foundation [1016720]
- Yale University
- NIH Director's Early Independence Award [DP5-OD023088]
- Robert T. McCluskey Foundation
- Artizan Biosciences
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The intestinal microbiota produces tens of thousands of metabolites. Here, we used host sensing of small molecules by G-protein coupled receptors (GPCRs) as a lens to illuminate bioactive microbial metabolites that impact host physiology. We screened 144 human gut bacteria against the non-olfactory GPCRome and identified dozens of bacteria that activated both well-characterized and orphan GPCRs, including strains that converted dietary histidine into histamine and shaped colonic motility; a prolific producer of the essential amino acid L-Phe, which we identified as an agonist for GPR56 and GPR97; and a species that converted L-Phe into the potent psychoactive trace amine phenethylamine, which crosses the blood-brain barrier and triggers lethal phenethylamine poisoning after monoamine oxidase inhibitor administration. These studies establish an orthogonal approach for parsing the microbiota metabolome and uncover multiple biologically relevant host-microbiota metabolome interactions.
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