Mapping Interactions of Microbial Metabolites with Human G-Protein-Coupled Receptors.

Autor:	Colosimo DA; Laboratory of Genetically Encoded Small Molecules, the Rockefeller University, 1230 York Avenue, New York City, NY 10065, USA., Kohn JA; Laboratory of Genetically Encoded Small Molecules, the Rockefeller University, 1230 York Avenue, New York City, NY 10065, USA., Luo PM; Laboratory of Genetically Encoded Small Molecules, the Rockefeller University, 1230 York Avenue, New York City, NY 10065, USA., Piscotta FJ; Laboratory of Genetically Encoded Small Molecules, the Rockefeller University, 1230 York Avenue, New York City, NY 10065, USA., Han SM; Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York City, NY 10029, USA., Pickard AJ; Donald B. and Catherine C. Marron Cancer Metabolism Center, Memorial Sloan Kettering Cancer Center, New York City, NY 10065, USA., Rao A; Donald B. and Catherine C. Marron Cancer Metabolism Center, Memorial Sloan Kettering Cancer Center, New York City, NY 10065, USA., Cross JR; Donald B. and Catherine C. Marron Cancer Metabolism Center, Memorial Sloan Kettering Cancer Center, New York City, NY 10065, USA., Cohen LJ; Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York City, NY 10029, USA., Brady SF; Laboratory of Genetically Encoded Small Molecules, the Rockefeller University, 1230 York Avenue, New York City, NY 10065, USA. Electronic address: sbrady@rockefeller.edu.
Jazyk:	angličtina
Zdroj:	Cell host & microbe [Cell Host Microbe] 2019 Aug 14; Vol. 26 (2), pp. 273-282.e7. Date of Electronic Publication: 2019 Aug 01.
DOI:	10.1016/j.chom.2019.07.002
Abstrakt:	Despite evidence linking the human microbiome to health and disease, how the microbiota affects human physiology remains largely unknown. Microbiota-encoded metabolites are expected to play an integral role in human health. Therefore, assigning function to these metabolites is critical to understanding these complex interactions and developing microbiota-inspired therapies. Here, we use large-scale functional screening of molecules produced by individual members of a simplified human microbiota to identify bacterial metabolites that agonize G-protein-coupled receptors (GPCRs). Multiple metabolites, including phenylpropanoic acid, cadaverine, 9-10-methylenehexadecanoic acid, and 12-methyltetradecanoic acid, were found to interact with GPCRs associated with diverse functions within the nervous and immune systems, among others. Collectively, these metabolite-receptor pairs indicate that diverse aspects of human health are potentially modulated by structurally simple metabolites arising from primary bacterial metabolism. (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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