論文 - 詳細
| RRC ID | 70312 |
|---|---|
| 著者 | Ye L, Bae M, Cassilly CD, Jabba SV, Thorpe DW, Martin AM, Lu HY, Wang J, Thompson JD, Lickwar CR, Poss KD, Keating DJ, Jordt SE, Clardy J, Liddle RA, Rawls JF. |
| タイトル | Enteroendocrine cells sense bacterial tryptophan catabolites to activate enteric and vagal neuronal pathways. |
| ジャーナル | Cell Host Microbe |
| Abstract |
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. |
| 巻・号 | 29(2) |
| ページ | 179-196.e9 |
| 公開日 | 2021-2-10 |
| DOI | 10.1016/j.chom.2020.11.011 |
| PII | S1931-3128(20)30633-8 |
| PMID | 33352109 |
| PMC | PMC7997396 |
| MeSH | Animals Animals, Genetically Modified Cholinergic Neurons / metabolism Edwardsiella tarda / metabolism* Enteric Nervous System / cytology Enteric Nervous System / metabolism* Enteroendocrine Cells / physiology* Gastrointestinal Motility / physiology Intestinal Mucosa / cytology Intestinal Mucosa / innervation Intestinal Mucosa / metabolism* Proto-Oncogene Proteins c-ret / genetics Serotonin / metabolism Signal Transduction TRPA1 Cation Channel / metabolism* Tryptophan / metabolism Zebrafish Zebrafish Proteins / genetics |
| IF | 15.923 |
| リソース情報 | |
| ゼブラフィッシュ | Tg(CM-isl1:GFP)rw0 |