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A Forward Chemical Genetic Screen Reveals Gut Microbiota Metabolites That Modulate Host Physiology.

Abstract：

: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.

journal_name

Cell

journal_title

Cell

authors

Chen H,Nwe PK,Yang Y,Rosen CE,Bielecka AA,Kuchroo M,Cline GW,Kruse AC,Ring AM,Crawford JM,Palm NW

doi

10.1016/j.cell.2019.03.036

subject

Has Abstract

pub_date

2019-05-16 00:00:00

pages

1217-1231.e18

issue

5

eissn

0092-8674

issn

1097-4172

pii

S0092-8674(19)30337-X

journal_volume

177

pub_type

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