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

Cell Host & Microbe
Dominic A ColosimoSean F Brady

Abstract

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.

References

Dec 1, 1979·Food and Cosmetics Toxicology·H Y Paik Jung, L F Bjeldanes
Apr 10, 2003·Chemical Reviews·Ludger A WessjohannThies Thiemann
Mar 31, 2004·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Ying-Jie LuCharles O Rock
Jun 1, 2004·Pharmacological Reviews·Paul J BrightonGary B Willars
Mar 16, 2007·Assay and Drug Development Technologies·Keith R Olson, Richard M Eglen
Mar 16, 2007·Journal of Medicinal Chemistry·Jae-Kyu JungGraeme Semple
Jul 4, 2008·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Melissa M Wagenaar
Dec 2, 2008·Nature·Peter J TurnbaughJeffrey I Gordon
Feb 25, 2009·Proceedings of the National Academy of Sciences of the United States of America·Yoko Irukayama-TomobeTakeshi Sakurai
May 22, 2009·Nature·Daniel M RosenbaumBrian K Kobilka
Oct 9, 2009·The Journal of Nutrition·Wai Mun LokeKevin D Croft
Jan 20, 2011·Proceedings of the National Academy of Sciences of the United States of America·Soumita DasJames E Casanova
Jun 16, 2012·Nature·UNKNOWN Human Microbiome Project Consortium
Jun 16, 2012·Nature·UNKNOWN Human Microbiome Project Consortium
Jan 26, 2013·Molecular Nutrition & Food Research·Wendy R RussellHarry J Flint
Sep 10, 2013·Journal of Agricultural and Food Chemistry·Irene Muñoz-GonzálezM Victoria Moreno-Arribas
Feb 11, 2014·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Soumita DasPeter B Ernst
May 13, 2014·Cell·Nicola GaglianiRichard A Flavell
Jun 5, 2014·Nature·Sathish SubramanianJeffrey I Gordon
Jun 21, 2014·Immunity·Pieter C DorresteinRob Knight
Nov 21, 2014·Nature Communications·Gautham V SridharanArul Jayaraman
Jan 24, 2015·Science·Mathias UhlénFredrik Pontén
May 28, 2016·Nature Reviews. Immunology·Michelle G Rooks, Wendy S Garrett
Aug 12, 2016·Journal of Cellular Physiology·Rahul MittalXue Zhong Liu
Oct 30, 2016·The American Journal of Medicine·Aakash GargEkaterina Sikorskaya
Nov 5, 2016·Cell·Gil SharonSarkis K Mazmanian
Dec 3, 2016·Nature Reviews. Drug Discovery·Rita SantosJohn P Overington
Jan 15, 2017·Trends in Endocrinology and Metabolism : TEM·Stefan Offermanns
Apr 5, 2017·Annual Review of Genomics and Human Genetics·Rob KnightMitchell L Sogin
Apr 9, 2017·The Journal of Biological Chemistry·J Mark Brown, Stanley L Hazen
Apr 11, 2017·European Journal of Nutrition·Ian RowlandKieran Tuohy
Nov 11, 2017·Cellular and Molecular Life Sciences : CMLS·Floor Hugenholtz, Willem M de Vos
Jan 5, 2018·Molecular Pharmacology·Krishna Sriram, Paul A Insel

❮ Previous
Next ❯

Citations

Feb 29, 2020·International Journal of Molecular Sciences·Nicola ForteLuigia Cristino
Apr 12, 2020·European Journal of Mass Spectrometry·Biswapriya B Misra
Sep 24, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Cristina Torres-FuentesHarriet Schellekens
Jun 6, 2020·Khirurgiia·D V IsakovG Yu Knorring
Aug 28, 2019·International Journal of Molecular Sciences·Romy AarnoutseMarjolein L Smidt
May 28, 2020·Frontiers in Physiology·Conor J BloxhamWalter G Thomas
Nov 27, 2019·Nature Reviews. Immunology·Wendy S Garrett
Sep 19, 2020·Science·Fyza Y Shaikh, Cynthia L Sears
Nov 16, 2019·Chembiochem : a European Journal of Chemical Biology·Zhenrun J ZhangHoward C Hang
Oct 7, 2020·Nature Communications·Aravind Natarajan, Ami S Bhatt
Nov 6, 2020·British Journal of Pharmacology·Farha Naz, Mohd Arish
Dec 30, 2020·Endocrinology·William Massey, J Mark Brown
Jan 7, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Hani Choudhry
Jan 23, 2021·Current Opinion in Endocrinology, Diabetes, and Obesity·Natasha K LeeuwendaalHarriët Schellekens
Mar 7, 2021·Communications Biology·Andrea NuzzoJames R Brown
Jan 26, 2021·Gastroenterology·Kara G MargolisEmeran A Mayer
Feb 19, 2021·Pharmacological Reviews·Mariana Angoa-Pérez, Donald M Kuhn
Mar 19, 2021·Molecular Systems Biology·Michael ZimmermannLisa Maier
Mar 23, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Aitak FarziHerbert Herzog
Mar 25, 2021·Nature Reviews. Nephrology·Jonathan D RavidVipul C Chitalia
Sep 12, 2020·Molecular Metabolism·Annick V HartstraMax Nieuwdorp
Sep 17, 2020·Immunity·Alexander LercherAndreas Bergthaler
May 18, 2021·The Journal of Clinical Investigation·Kristie B Yu, Elaine Y Hsiao
May 18, 2021·The Journal of Clinical Investigation·Alyssa SchledwitzJean-Pierre Raufman
Jun 27, 2021·Experimental Dermatology·Abigail E EliasCatherine A O'Neill
Aug 20, 2020·Immunity·Margaret Alexander, Peter J Turnbaugh
Sep 22, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jason D Bishai, Noah W Palm
Oct 8, 2021·Nature Communications·Yuki FujiwaraYuwen Zhu
Aug 5, 2021·Annual Review of Microbiology·Graham J Britton, Jeremiah J Faith

❮ Previous
Next ❯

Methods Mentioned

BETA
NMR
PCR
reverse phase chromatography

Software Mentioned

MassHunter Quantitative Analysis
MassHunter Profinder
PathHunter
Eurofins DiscoverX
GraphPad Prizm
TraceFinder

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.