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

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2019 Apr 23

PMID 31006530

Citations 145

Authors

Haiwei Chen

Phu-Khat Nwe

Yi Yang

Connor E Rosen

Agata A Bielecka

Manik Kuchroo

Gary W Cline

Andrew C Kruse

Aaron M Ring

Jason M Crawford

Noah W Palm

Affiliations

Soon will be listed here.

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.

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