Commensal bacteria make GPCR ligands that mimic human signalling molecules

Cohen, Louis J.; Esterhazy, Daria; Kim, Seong-Hwan; Lemetre, Christophe; Aguilar, Rhiannon R.; Gordon, Emma A.; Pickard, Amanda J.; Cross, Justin R.; Emiliano, Ana B.; Han, Sun M.; Chu, John; Vila-Farres, Xavier; Kaplitt, Jeremy; Rogoz, Aneta; Calle, Paula Y.; Hunter, Craig; Bitok, J. Kipchirchir; Brady, Sean F.

doi:10.1038/nature23874

Cited by 500Gut microbiota and healthMicrobial Natural Products and BiosynthesisGastrointestinal motility and disorders

Commensal bacteria make GPCR ligands that mimic human signalling molecules

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Cohen, Louis J., Esterhazy, Daria, Kim, Seong-Hwan, Lemetre, Christophe, Aguilar, Rhiannon R., Gordon, Emma A., Pickard, Amanda J., Cross, Justin R. +10 more·2017·Nature

DOI 10.1038/nature23874PMC PMC5777231

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Abstract

Commensal bacteria are believed to have important roles in human health. The mechanisms by which they affect mammalian physiology remain poorly understood, but bacterial metabolites are likely to be key components of host interactions. Here we use bioinformatics and synthetic biology to mine the human microbiota for N-acyl amides that interact with G-protein-coupled receptors (GPCRs). We found that N-acyl amide synthase genes are enriched in gastrointestinal bacteria and the lipids that they encode interact with GPCRs that regulate gastrointestinal tract physiology. Mouse and cell-based models demonstrate that commensal GPR119 agonists regulate metabolic hormones and glucose homeostasis as efficiently as human ligands, although future studies are needed to define their potential physiological role in humans. Our results suggest that chemical mimicry of eukaryotic signalling molecules may be common among commensal bacteria and that manipulation of microbiota genes encoding metabolites that elicit host cellular responses represents a possible small-molecule therapeutic modality (microbiome-biosynthetic gene therapy).

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Commensal bacteria are able to produce G-protein-coupled receptor agonists to regulate GI tract physiology, including metabolic hormones and glucose homeostasis.
“Moreover, a recent paper described that commensal bacteria are able to produce G-protein-coupled receptor agonists to regulate the GI tract physiology, including metabolic hormones and glucose homeostasis [4].”
From Anxiety, depression, and the microbiome: A role for gut peptides (2018) · cites this paper as [4]
Microbes secrete eCBs.
“Although microbes secrete eCBs, their role in host physiology remains unclear (255).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [255]

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A review about commensal bacteria making GPCR ligands that mimic human signaling molecules
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Authors: Cohen, L. J., Esterhazy, D., Kim, S.-H., Lemetre, C., Aguilar, R. R., Gordon, E. A., Pickard, A. J., Cross, J. R., Emiliano, A. B., Han, S. M., Chu, J., Vila-Farres, X., Kaplitt, J., Rogoz, A., Calle, P. Y., Hunter, C., Bitok, J. K., & Brady, S. F.
Affiliations: Rockefeller University (US)
Memorial Sloan Kettering Cancer Center (US)
Corresponding author: Brady, Sean F.
ORCID: Cohen, Louis J.
Kim, Seong-Hwan
Aguilar, Rhiannon R.
Gordon, Emma A.
Pickard, Amanda J.
Cross, Justin R.
Emiliano, Ana B.
Brady, Sean F.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2017-08-30
Volume: 549
Issue: 7670
Pages: 48-53
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature23874
PMC: PMC5777231
OpenAlex: W2753100975
Cited by: 500
References: 45
Citations by year: 2026: 44 · 2025: 47 · 2024: 60 · 2023: 53 · 2022: 52 · 2021: 44 · 2020: 64 · 2019: 62 · 2018: 55 · 2017: 18
FWCI: 22.22
Type: journal article
Language: en
Update notices: erratum (2018-04-05)
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Funders: Crohn's and Colitis Foundation (370629)
National Institute of General Medical Sciences (U01GM110714, R35GM122559)
National Institute of Diabetes and Digestive and Kidney Diseases (T32DK007792, K08DK109287)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Health Sciences › Medicine › Pharmacology › Microbial Natural Products and Biosynthesis
Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
Keywords: commensal bacteria, G protein-coupled receptors, GPR119, gut microbiota metabolites, glucose homeostasis, metabolic hormones, gastrointestinal tract physiology
MeSH terms: Biological Mimicry, Gastrointestinal Microbiome, Amides, Animals, Bacteria, Blood Glucose, Female, Homeostasis, Humans, Ligands, Male, Symbiosis, Signal Transduction, Gastrointestinal Tract, Receptors, G-Protein-Coupled, Mice, HEK293 Cells

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