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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Ye, L; Bae, M; Cassilly, CD; Jabba, SV; Thorpe, DW; Martin, AM; Lu, H-Y; Wang, J; Thompson, JD; Lickwar, CR; Poss, KD; Keating, DJ; Jordt, S-E; Clardy, J; Liddle, RA; Rawls, JF

Published Date

  • February 10, 2021

Published In

Volume / Issue

  • 29 / 2

Start / End Page

  • 179 - 196.e9

PubMed ID

  • 33352109

Pubmed Central ID

  • 33352109

Electronic International Standard Serial Number (EISSN)

  • 1934-6069

Digital Object Identifier (DOI)

  • 10.1016/j.chom.2020.11.011

Language

  • eng

Conference Location

  • United States