Format

Send to

Choose Destination
Cell. 2019 May 16;177(5):1217-1231.e18. doi: 10.1016/j.cell.2019.03.036. Epub 2019 Apr 18.

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

Author information

1
Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.
2
Chemical Biology Institute and Department of Chemistry, Yale University, West Haven and New Haven, CT, USA.
3
Yale University School of Medicine, New Haven, CT, USA.
4
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA.
5
Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
6
Chemical Biology Institute and Department of Chemistry, Yale University, West Haven and New Haven, CT, USA; Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT, USA.
7
Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA. Electronic address: noah.palm@yale.edu.

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.

PMID:
31006530
PMCID:
PMC6536006
[Available on 2020-05-16]
DOI:
10.1016/j.cell.2019.03.036

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center