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Author Notes:

John F. Rawls, Email: john.rawls@duke.edu

Conceptualization: L.Y., R.L., J.R.; Formal Analysis: L.Y., S.J., M.B., C.C., C.L.; Funding acquisition: K.P., D.J., S.-E.J., R.L., J.R.; Investigation: L.Y., S.J., M.B., C.C., D.T., A.M., H.L., J. C., D.K.; Methodology: L.Y., S.J., M.B., C.C., D.T., A.M., D.K.; Resources: L.Y., J. W., J.T., K.P.; Supervision: J.C., R.L., J.R.; Visualization: L.Y., S.J., M.B.; Writing – original draft: L.Y.; Writing – review & editing: L.Y., R.L., J.R., K.P., C.L..

The authors declare no competing interests.


Research Funding:

This work was supported by NIH R01-DK093399, R01-DK109368, VA-BX002230, and a Pew Scholars Innovation Award from the Pew Charitable Trusts. S.V.J. and S.-E.J. were supported by cooperative agreement U01ES030672 of the NIH CounterACT Program. K.D.P. was supported by R01 GM074057 and R35 HL150713. L.Y. was supported by NIH T32-DK007568. C. D.C. was supported by NIH F32AT010415. D.J.K. was supported by the Australian Research Council, DP190103525. We are grateful to Cecelia Kelly for assistance in mouse experiments, and other members of the Rawls and Liddle labs for feedback and support. The content is solely the responsibility of the authors and does not necessarily represent the views of the NIH.


  • Science & Technology
  • Life Sciences & Biomedicine
  • Microbiology
  • Parasitology
  • Virology
  • GUT

Enteroendocrine cells sense bacterial tryptophan catabolites to activate enteric and vagal neuronal pathways

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Journal Title:



Volume 29, Number 2


, Pages 179-+

Type of Work:

Article | Post-print: After Peer Review


The intestinal epithelium senses nutritional and microbial stimuli using epithelial sensory enteroendocrine cells (EEC). EECs communicate nutritional information to the nervous system, but whether they also relay signals from intestinal microbes remains unknown. Using in vivo real-time measurements of EEC and nervous system activity in zebrafish, we discovered that the bacteria Edwardsiella tarda activate EECs through the receptor transient receptor potential ankyrin A1 (Trpa1) and increase intestinal motility. Microbial, pharmacological, or optogenetic activation of Trpa1+EECs directly stimulates vagal sensory ganglia and activates cholinergic enteric neurons by secreting the neurotransmitter 5-hydroxytryptamine (5-HT). A subset of indole derivatives of tryptophan catabolism produced by E. tarda and other gut microbes activates zebrafish EEC Trpa1 signaling. These catabolites also directly stimulate human and mouse Trpa1 and intestinal 5-HT secretion. These results establish a molecular pathway by which EECs regulate enteric and vagal neuronal pathways in response to microbial signals.

Copyright information:

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/rdf).
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