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

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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., 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.·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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Fu, J., Gaetani, S., Oveisi, F., Verme, J., Serrano, A., de Fonseca, F. D., Rosengarth, A., Luecke, H., Giacomo, B. D., Tarzia, G., et al. (2003) · Nature · doi:10.1038/nature01921 · Cited by 1,113
Relating the metatranscriptome and metagenome of the human gut
Franzosa, E. A., Morgan, X. C., Segata, N., Waldron, L., Reyes, J. A., Earl, A. M., Giannoukos, G., Boylan, M. R., Ciulla, D., Gevers, D., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1319284111 · Cited by 731
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Overton, H. A., Babbs, A. J., Doel, S. M., Fyfe, M. C. T., Gardner, L. S., Griffin, G., Jackson, H. C., Procter, M. J., Rasamison, C. M., Tang‐Christensen, M., et al. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.02.004 · Cited by 670
The prostaglandin receptor EP4 suppresses colitis, mucosal damage and CD4 cell activation in the gut
Kabashima, K., Saji, T., Murata, T., Nagamachi, M., Matsuoka, T., Segi‐Nishida, E., Tsuboi, K., Sugimoto, Y., Kobayashi, T., Miyachi, Y., et al. (2002) · Journal of Clinical Investigation · doi:10.1172/jci14459 · Cited by 443
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Pacher, P., & Kunos, G. (2013) · FEBS Journal · doi:10.1111/febs.12260 · Cited by 418
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Kabashima, K., Saji, T., Murata, T., Nagamachi, M., Matsuoka, T., Segi‐Nishida, E., Tsuboi, K., Sugimoto, Y., Kobayashi, T., Miyachi, Y., et al. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0214459 · Cited by 418
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Lauffer, L. M., Iakoubov, R., & Brubaker, P. L. (2009) · Diabetes · doi:10.2337/db08-1237 · Cited by 405
A Role for Intestinal Endocrine Cell-Expressed G Protein-Coupled Receptor 119 in Glycemic Control by Enhancing Glucagon-Like Peptide-1 and Glucose-Dependent Insulinotropic Peptide Release
Chu, Z., Carroll, C., Alfonso, J., Gutierrez, V., He, H., Lucman, A., Pedraza, M., Mondala, H., Gao, H., Bagnol, D., et al. (2008) · Endocrinology · doi:10.1210/en.2007-0966 · Cited by 387
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“In fact, bacteria-derived N -acyl amides interact with host G-protein coupled receptors (GPCRs), including N -palmitoyl serinol with GPR119, N -3-hydroxypalmitoyl ornithine with S1PR4, and N -myristoyl alanine with G2A, leading to regulation of glucose (102).”
Isolation and Structure Determination of a New Lumichrome Glycoside Isolated from a Soil Streptomyces sp. KCB16C001
Son, S., Kim, E. Y., Kim, J., Ko, S., Lee, B., Lee, J., Hong, Y., Jang, J., & Ahn, J. S. (2018) · Natural Product Communications · doi:10.1177/1934578x1801300211 · Cited by 3
Gut Homeostasis; Microbial Cross Talks in Health and Disease Management
Khatri, G. S., Kurian, C., Anand, A., & Paari, K. A. (2021) · Current Research in Nutrition and Food Science Journal · doi:10.12944/crnfsj.9.3.28 · Cited by 3
Molecular networking in infectious disease models
Harris, M. B., Lesani, M., Liu, Z., & McCall, L. (2022) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/bs.mie.2021.09.018 · Cited by 4
Healthy plant-based diet might be inversely associated with gastric precancerous lesions: new evidence from a case-control study based on dietary pattern and fecal metabolic profiling
Cheng, W., Lin, X., Wang, T., Zhang, X., Xu, F., Wang, L., Wang, M., Zhang, M., Xia, T., Zhang, D., et al. (2023) · International Journal of Food Sciences and Nutrition · doi:10.1080/09637486.2023.2279916 · Cited by 3
“N-acyl amides have also been shown to play a role in cell migration, inflammation, and certain pathological conditions, such as diabetes, cancer, neuro-degenerative disease, and obesity (Grapov et al. 2012; Raboune et al. 2014; Cohen et al. 2017).”
Background
Distinctive Lipid Characteristics of Colorectal Cancer Revealed through Non-targeted Lipidomics Analysis of Tongue Coating
Chen, Q., Lin, F., Li, W., Gu, X., Chen, Y., Su, H., Zhang, L., Zheng, W. L., Zeng, X., Lu, X., et al. (2024) · Journal of Proteome Research · doi:10.1021/acs.jproteome.4c00063 · Cited by 3
Identifying and Filling the Chemobiological Gaps of Gut Microbial Metabolites
Orgaz, C., Sánchez-Ruiz, A., & Colmenarejo, G. (2024) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.4c00903 · Cited by 3
Topical applications of a novel formulation improve epidermal permeability barrier in chronologically aged humans
Zhao, J., Zhang, Y., Li, Y., Zhang, G., & Man, M. (2021) · Journal of Cosmetic Dermatology · doi:10.1111/jocd.14571 · Cited by 3
Behavioral Risk Factors
Thiriet, M. (2018) · Biomathematical and biomechanical modeling of the circulatory and ventilatory systems · doi:10.1007/978-3-319-89315-0_6 · Cited by 3
Emerging clinical pharmacology topics in drug development and precision medicine
Liu, Q., Gilbert, J. A., Zhu, H., Huang, S. M., Kunkoski, E., Das, P., Bergman, K. L., Buschmann, M. M., & ElZarrad, M. K. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-819869-8.00028-8 · Cited by 3
Gnotobiotic experimentation helps define symbiogenesis in vertebrate evolution
Tannock, G. W. (2023) · New Zealand Journal of Zoology · doi:10.1080/03014223.2023.2169943 · Cited by 3
“Some of these receptors are located in the intestinal epithelium and several bind small-molecule therapeutic agents (Cohen et al. 2017).”
Screening for bacterial enzymes synthesizing GPR119 agonist in cAMP-responsive cells
Jia, J., Chen, Y., Xu, L., Yang, Y., Xu, X., Ding, H., Jia, C., Gao, H., Guo, P., & Hu, R. (2020) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gmaa144 · Cited by 3
Host interactions of bioactive molecules produced by Klebsiella spp
McCartney, A. L., & Hoyles, L. (2025) · Microbiota and Host · doi:10.1530/mah-24-0011 · Cited by 3
Design of a Continuous GAA-Producing Probiotic as a Potential Mitigator of the Effects of Sleep Deprivation
Fields, B. D., Pascal, D. G., Rando, O. K., Huddleston, M., Ingram, K., Hopton, R., Grogg, M. W., Nelson, M., & Voigt, C. A. (2025) · ACS Synthetic Biology · doi:10.1021/acssynbio.4c00690 · Cited by 2
Abnormal Gut Microbiota is Associated with Depressive-like Behavior in the Rat Model of Autoimmune Prostatitis
Wang, Y., Zhu, X., He, Y., Lu, W., Wang, Z., & Liu, F. (2025) · Applied Biochemistry and Biotechnology · doi:10.1007/s12010-025-05294-1 · Cited by 2
“Recent studies suggested that gut dysbiosis may contribute to the pathological progression of prostatitis through the "gut-prostate axis” [35, 41].”
Lipidomics, Microbiota, and Intestinal Clostridioides difficile Infection Outcome
Branković, M., Kraišnik, M., Zdravković, D., Kraišnik, N., Jelić, F., Nikolić, N., Djurasevic, S. F., Tosti, T. B., Gmizić, T., & Todorović, Z. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26178214 · Cited by 2
Microbial-derived immunostimulatory small molecule augments anti-PD-1 therapy in lung cancer
Newsome, R. C., Liu, H., Agbodzi, B., Gharaibeh, R. Z., Zhou, L., & Jobin, C. (2025) · Cell Reports Medicine · doi:10.1016/j.xcrm.2025.102519 · Cited by 3
Significance of neuroendocrine systems and the gut-brain axis (GBA) in the regulation of obesity
Zhao, H., Li, Y., Cheng, R., Wang, Y., Ma, L., & Chen, W. (2026) · PeerJ · doi:10.7717/peerj.20400 · Cited by 3
Identification of the cannabinoid receptor 1 antagonist, ibipinabant, as a potent inhibitor of Neisseria gonorrhoeae
Dove, A. S., Abdelsattar, A. S., Abutaleb, N. S., & Seleem, M. N. (2026) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01231-25 · Cited by 2
“It has been shown that some bacteria that comprise the gut microbiota can produce small molecules that act as ligands for GPCRs, thus modulating human-microbe interactions (14, 15).”
Cranberry extract-supplemented microbiota effluents enhance intestinal barrier integrity via mucin production and antimicrobial activity in murine organoids
Cattero, V., Mayer, T., Veilleux, A., Roussel, C., & Desjardins, Y. (2026) · Scientific Reports · doi:10.1038/s41598-026-39008-2 · Cited by 2
“Indeed, GPR109 has been shown to be activated by endocannabinoidome-like lipids produced by the gut microbiota 52,99–102 and to be involved in crosstalk with GPR55 signaling pathways 103 .”
Metabotherapy for intestinal disease: using metabolites to prevent and treat disorders of the gut
Liu, S., Domingo‐Vidal, M., Madhu, B., Binyamin, D., Thaiss, C. A., & Levy, M. (2026) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-026-01178-9 · Cited by 5
“These bioactive molecules highlight a promising therapeutic strategy for IBD by harnessing microbial production of host receptor agonists 26 .”
Diet and Childhood Obesity: The Mediating Role of the Gut Microbiota
Zhang, S., Wang, B., Chen, Z., Lyu, J., Fan, F., & Han, F. (2026) · International Journal for Vitamin and Nutrition Research · doi:10.31083/ijvnr41881 · Cited by 2
Commensal-derived acetylcholine enhances mucosal immune education
Song, D., Lowey, B., Khetrapal, V., Hamchand, R., Deng, T., Brown, H. M., Wu, A., Martin, A. L., Bauer, K. M., Zhao, Y., et al. (2026) · Nature · doi:10.1038/s41586-026-10592-7 · Cited by 3
The Xenorhabdus nematophila LrhA transcriptional regulator modulates production of γ-keto- N -acyl amides with inhibitory activity against mutualistic host nematode egg hatching
Lam, Y. C., Hamchand, R., Mucci, N. C., Kauffman, S., Dudkina, N., Reagle, E. V., Casanova‐Torres, Á. M., DeCuyper, J., Chen, H., Song, D., et al. (2024) · Applied and Environmental Microbiology · doi:10.1128/aem.00528-24 · Cited by 2
Characterization of a new lyso-ornithine lipid from the shipworm symbiont Teredinibacter turnerae
Pineda, E. G. S., Peran, J. E., Batucan, J. D., Acyatan, Z. G., Susana-Guevarra, S. R., & Salvador‐Reyes, L. A. (2025) · Phytochemistry Letters · doi:10.1016/j.phytol.2025.102960 · Cited by 2
Microbiome and Early Life
Hornef, M. W. (2018) · Springer eBooks · doi:10.1007/978-3-319-90545-7_3 · Cited by 3
The microbiome and cardiovascular disease: Implications in Precision Medicine
Wang, Z., & Osborn, L. J. (2023) · Elsevier eBooks · doi:10.1016/b978-0-12-824010-6.00022-8 · Cited by 2
Copy-catting host signalling molecules
York, A. (2017) · Nature Reviews Microbiology · doi:10.1038/nrmicro.2017.115 · Cited by 2
Next-generation microbial drugs developed from microbiome's natural products
Bhattarai, K., Bhattarai, K., & Baral, B. (2021) · Advances in genetics · doi:10.1016/bs.adgen.2021.08.007 · Cited by 2
Anti‐Diabetic Intestinal Mechanisms: Foods, Herbs, and Western Medicines
Feng, Y., Cao, H., Hua, J., & Zhang, F. (2022) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.202200106 · Cited by 2
Characterization of the role of glycine lipids in Bacteroides thetaiotaomicronPreprint
Lynch, A., Tammireddy, S. R., Doherty, M. K., Whitfield, P. D., & Clarke, D. J. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/371807 · Cited by 2
The Kidney in Liver Disease
Levi, M., Takahashi, S., Wang, X. X., & Levi, M. E. (2020) · doi:10.1002/9781119436812.ch49 · Cited by 2
A fluorescent fingerprint recording strategy for complex chemical solution
Duan, Q., Lee, J., Zheng, C., Zheng, Y., & Chen, H. (2019) · Analytical Methods · doi:10.1039/c8ay02702a · Cited by 1
Host-microbial interactions in the esophagus
Ebigbo, N., & Souza, R. F. (2025) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00079.2025 · Cited by 1
Dietary Manganese Modulates Microbiota and Intestinal N ‐Acylethanolamines in a Sex‐Specific Manner in Mice With Diet‐Induced Obesity
Agudelo, F. A. G., Leblanc, N., Bourdeau‐Julien, I., St‐Arnaud, G., Dahhani, F., Flamand, N., Veilleux, A., Marzo, V. D., & Raymond, F. (2025) · The FASEB Journal · doi:10.1096/fj.202500934r · Cited by 1

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
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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