The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.
Commensal bacteria make GPCR ligands that mimic human signalling molecules
Open accessAbstract
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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“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]
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“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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The prostaglandin receptor EP4 suppresses colitis, mucosal damage and CD4 cell activation in the gut
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Trends in GPCR drug discovery: new agents, targets and indications
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Metadata
- 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
- Venue
- Nature
- Published
- 2017-08-30
- Volume
- 549
- Issue
- 7670
- Pages
- 48-53
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- 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
- 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
- Life Sciences › Immunology and Microbiology › Applied Microbiology and Biotechnology › 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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