Vasoactive Intestinal Polypeptide Plays a Key Role in the Microbial-Neuroimmune Control of Intestinal MotilitySummary

Xiaopeng Bai; Giada De Palma; Elisa Boschetti; Yuichiro Nishiharo; Jun Lu; Chiko Shimbori; Anna Costanzini; Zarwa Saqib; Narjis Kraimi; Sacha Sidani; Siegfried Hapfelmeier; Andrew J. Macpherson; Elena F. Verdu; Roberto De Giorgio; Stephen M. Collins; Premysl Bercik

Cellular and Molecular Gastroenterology and Hepatology (Jan 2024)

Vasoactive Intestinal Polypeptide Plays a Key Role in the Microbial-Neuroimmune Control of Intestinal MotilitySummary

Xiaopeng Bai,
Giada De Palma,
Elisa Boschetti,
Yuichiro Nishiharo,
Jun Lu,
Chiko Shimbori,
Anna Costanzini,
Zarwa Saqib,
Narjis Kraimi,
Sacha Sidani,
Siegfried Hapfelmeier,
Andrew J. Macpherson,
Elena F. Verdu,
Roberto De Giorgio,
Stephen M. Collins,
Premysl Bercik

Affiliations

Xiaopeng Bai: Farncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada; Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Giada De Palma: Farncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada
Elisa Boschetti: Department of Biomedical and NeuroMotor Sciences, University of Bologna, Bologna, Italy
Yuichiro Nishiharo: Farncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada
Jun Lu: Farncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada
Chiko Shimbori: Farncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada
Anna Costanzini: IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
Zarwa Saqib: Farncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada
Narjis Kraimi: Farncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada
Sacha Sidani: Farncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada
Siegfried Hapfelmeier: Institute for Infectious Diseases, University of Bern, Bern, Switzerland
Andrew J. Macpherson: Department of Biomedical Research, University Hospital of Bern, Bern, Switzerland
Elena F. Verdu: Farncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada
Roberto De Giorgio: Department of Translational Medicine, University of Ferrara, Ferrara, Italy
Stephen M. Collins: Farncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada
Premysl Bercik: Farncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada; Correspondence Address correspondence to: Premysl Bercik, MD, Farncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, HSC 3N9, Hamilton, Ontario, Canada.

Journal volume & issue: Vol. 17, no. 3
pp. 383 – 398

Abstract

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Background & Aims: Although chronic diarrhea and constipation are common, the treatment is symptomatic because their pathophysiology is poorly understood. Accumulating evidence suggests that the microbiota modulates gut function, but the underlying mechanisms are unknown. We therefore investigated the pathways by which microbiota modulates gastrointestinal motility in different sections of the alimentary tract. Methods: Gastric emptying, intestinal transit, muscle contractility, acetylcholine release, gene expression, and vasoactive intestinal polypeptide (VIP) immunoreactivity were assessed in wild-type and Myd88-/-Trif-/- mice in germ-free, gnotobiotic, and specific pathogen-free conditions. Effects of transient colonization and antimicrobials as well as immune cell blockade were investigated. VIP levels were assessed in human full-thickness biopsies by Western blot. Results: Germ-free mice had similar gastric emptying but slower intestinal transit compared with specific pathogen-free mice or mice monocolonized with Lactobacillus rhamnosus or Escherichia coli, the latter having stronger effects. Although muscle contractility was unaffected, its neural control was modulated by microbiota by up-regulating jejunal VIP, which co-localized with and controlled cholinergic nerve function. This process was responsive to changes in the microbial composition and load and mediated through toll-like receptor signaling, with enteric glia cells playing a key role. Jejunal VIP was lower in patients with chronic intestinal pseudo-obstruction compared with control subjects. Conclusions: Microbial control of gastrointestinal motility is both region- and bacteria-specific; it reacts to environmental changes and is mediated by innate immunity-neural system interactions. By regulating cholinergic nerves, small intestinal VIP plays a key role in this process, thus providing a new therapeutic target for patients with motility disorders.

Published in Cellular and Molecular Gastroenterology and Hepatology

ISSN: 2352-345X (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the digestive system. Gastroenterology
Website: https://www.journals.elsevier.com/cellular-and-molecular-gastroenterology-and-hepatology/

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