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

Cell Reports (Apr 2024)

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

Affiliations

Jessica A. Griffiths: Division of Biology & Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA; Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA
Bryan B. Yoo: Division of Biology & Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA
Peter Thuy-Boun: Departments of Molecular Medicine and Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Victor J. Cantu: Department of Pediatrics, University of California, San Diego, San Diego, CA, USA
Kelly C. Weldon: Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, San Diego, CA, USA; UCSD Center for Microbiome Innovation, University of California, San Diego, San Diego, CA, USA
Collin Challis: Division of Biology & Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA
Michael J. Sweredoski: Division of Biology & Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA
Ken Y. Chan: Division of Biology & Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA
Taren M. Thron: Division of Biology & Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA
Gil Sharon: Division of Biology & Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA
Annie Moradian: Division of Biology & Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA
Gregory Humphrey: Department of Pediatrics, University of California, San Diego, San Diego, CA, USA
Qiyun Zhu: Department of Pediatrics, University of California, San Diego, San Diego, CA, USA
Justin P. Shaffer: Department of Pediatrics, University of California, San Diego, San Diego, CA, USA
Dennis W. Wolan: Departments of Molecular Medicine and Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Pieter C. Dorrestein: Department of Pediatrics, University of California, San Diego, San Diego, CA, USA; Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, San Diego, CA, USA; UCSD Center for Microbiome Innovation, University of California, San Diego, San Diego, CA, USA
Rob Knight: Department of Pediatrics, University of California, San Diego, San Diego, CA, USA; UCSD Center for Microbiome Innovation, University of California, San Diego, San Diego, CA, USA; Department of Computer Science and Engineering, University of California, San Diego, San Diego, CA, USA; Shu Chien-Gene Lay Department of Engineering, University of California, San Diego, San Diego, CA, USA; Halıcıoğlu Data Science Institute, University of California, San Diego, San Diego, CA, USA
Viviana Gradinaru: Division of Biology & Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA; Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA
Sarkis K. Mazmanian: Division of Biology & Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA; Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA; Corresponding author

Journal volume & issue: Vol. 43, no. 4
p. 113953

Abstract

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Summary: 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.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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