• A Corrigendum to this article was published on 04 April 2018

This article has been updated


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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Change history

  • 04 April 2018

    Please see accompanying Corrigendum (http://doi.org/10.1038/nature25997).The description in the Methods of the human stool samples used for the analysis presented in Extended Data Figure 9 has been corrected, with patient age, gender and transplant indication provided in the table now added to Extended Data Fig. 9. The Reporting Summary has been updated. The original Article has been corrected online.


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We thank the High-Throughput and Spectroscopy Resource Center, Center for Clinical and Translational Science and the Comparative Bioscience Center at Rockefeller University for the use of their facilities; members of the Mangelsdorf laboratory at UT Southwestern and D. Drucker at Mount Sinai Hospital, Toronto for the use of the GLUTag cell line; A. Milshteyn, A. Estrela and J. Craig for their critical review of the manuscript. This work was supported in part by a grant from the Robertson Foundation, the Center for Basic and Translational Research on Disorders of the Digestive System, the Leona M. and Harry B. Helmsley Charitable Trust, Rainin Foundation, U01 GM110714-1A1 (S.F.B.), GM122559-01 (S.F.B.), the Crohn’s and Colitis Foundation Career Development Award (L.J.C.) and NIDDK K08 DK109287-01 (L.J.C.).

Author information


  1. Laboratory of Genetically Encoded Small Molecules, Rockefeller University, New York, New York 10065, USA

    • Louis J. Cohen
    • , Seong-Hwan Kim
    • , Christophe Lemetre
    • , Rhiannon R. Aguilar
    • , Emma A. Gordon
    • , Sun M. Han
    • , John Chu
    • , Xavier Vila-Farres
    • , Jeremy Kaplitt
    • , Paula Y. Calle
    • , J. Kipchirchir Bitok
    •  & Sean F. Brady
  2. Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA

    • Louis J. Cohen
  3. Laboratory of Mucosal Immunology, Rockefeller University, New York, New York 10065, USA

    • Daria Esterhazy
    •  & Aneta Rogoz
  4. Donald B. and Catherine C. Marron Cancer Metabolism Center, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA

    • Amanda J. Pickard
    •  & Justin R. Cross
  5. Laboratory of Molecular Genetics, Rockefeller University, New York, New York 10065, USA

    • Ana B. Emiliano
  6. Comparative Biosciences Center, Rockefeller University, New York, New York 10065, USA

    • Craig Hunter


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L.J.C. and S.F.B. designed research; L.J.C. assisted with all experiments; S.-H.K. assisted with molecule characterization; E.A.G., P.Y.C., J.K.B. and R.R.A. assisted with gene cloning; D.E., A.B.E., S.M.H., C.H. and A.R. assisted with mouse experiments; J.C., X.V.-F., J.K. assisted with molecule synthesis; A.J.P. and J.R.C. assisted with metabolite analysis in human and mouse samples; L.J.C. and C.L. analysed data; L.J.C. and S.F.B. wrote the paper.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Sean F. Brady.

Reviewer Information Nature thanks D. J. Drucker and the other anonymous reviewer(s) for their contribution to the peer review of this work.

Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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