Peripheral neuronal activation shapes the microbiome and alters gut physiology

Jessica A. Griffiths, Bryan B. Yoo, Peter Thuy-Boun, Victor J. Cantu, Kelly C. Weldon, Collin Challis, Michael J. Sweredoski, Ken Y. Chan, Taren M. Thron, Gil Sharon, Annie Moradian, Gregory Humphrey, Qiyun Zhu, Justin P. Shaffer, Dennis W. Wolan, Pieter C. Dorrestein, Rob Knight, Viviana Gradinaru, Sarkis K. Mazmanian

Research output: Contribution to journalArticlepeer-review


The gastrointestinal (GI) tract is innervated by intrinsic neurons of the enteric nervous system (ENS) and extrinsic neurons of the central nervous system and peripheral ganglia. The GI tract also harbors a diverse microbiome, but interactions between the ENS and the microbiome remain poorly understood. Here, we activate choline acetyltransferase (ChAT)-expressing or tyrosine hydroxylase (TH)-expressing gut-associated neurons in mice to determine effects on intestinal microbial communities and their metabolites as well as on host physiology. The resulting multi-omics datasets support broad roles for discrete peripheral neuronal subtypes in shaping microbiome structure, including modulating bile acid profiles and fungal colonization. Physiologically, activation of either ChAT+ or TH+ neurons increases fecal output, while only ChAT+ activation results in increased colonic contractility and diarrhea-like fluid secretion. These findings suggest that specific subsets of peripherally activated neurons differentially regulate the gut microbiome and GI physiology in mice without involvement of signals from the brain.

Original languageEnglish
Article number113953
JournalCell Reports
Issue number4
StatePublished - 23 Apr 2024
Externally publishedYes


  • Akkermansia muciniphila
  • CP: Microbiology
  • CP: Neuroscience
  • cholinergic
  • dopaminergic
  • enteric nervous system
  • gut microbiome
  • gut motility
  • noradrenergic
  • peripheral nervous system


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