Saccharomyces boulardii CNCM I-745 modulates the microbiota-gut-brain axis in a humanized mouse model of Irritable Bowel Syndrome

Neurogastroenterol Motil. 2021 Mar;33(3):e13985. doi: 10.1111/nmo.13985. Epub 2020 Sep 21.

Abstract

Background: Gnotobiotic mice colonized with microbiota from patients with irritable bowel syndrome (IBS) and comorbid anxiety (IBS+A) display gut dysfunction and anxiety-like behavior compared to mice colonized with microbiota from healthy volunteers. Using this model, we tested the therapeutic potential of the probiotic yeast Saccharomyces boulardii strain CNCM I-745 (S. bou) and investigated underlying mechanisms.

Methods: Germ-free Swiss Webster mice were colonized with fecal microbiota from an IBS+A patient or a healthy control (HC). Three weeks later, mice were gavaged daily with S. boulardii or placebo for two weeks. Anxiety-like behavior (light preference and step-down tests), gastrointestinal transit, and permeability were assessed. After sacrifice, samples were taken for gene expression by NanoString and qRT-PCR, microbiota 16S rRNA profiling, and indole quantification.

Key results: Mice colonized with IBS+A microbiota developed faster gastrointestinal transit and anxiety-like behavior (longer step-down latency) compared to mice with HC microbiota. S. bou administration normalized gastrointestinal transit and anxiety-like behavior in mice with IBS+A microbiota. Step-down latency correlated with colonic Trpv1 expression and was associated with altered microbiota profile and increased Indole-3-acetic acid (IAA) levels.

Conclusions & inferences: Treatment with S. bou improves gastrointestinal motility and anxiety-like behavior in mice with IBS+A microbiota. Putative mechanisms include effects on pain pathways, direct modulation of the microbiota, and indole production by commensal bacteria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anxiety / microbiology*
  • Anxiety / physiopathology
  • Brain / metabolism
  • Brain / physiopathology*
  • Case-Control Studies
  • Colon / metabolism
  • Fecal Microbiota Transplantation
  • Gastrointestinal Microbiome / physiology*
  • Gastrointestinal Transit / physiology*
  • Germ-Free Life
  • Humans
  • Indoleacetic Acids / metabolism
  • Intestinal Mucosa / metabolism*
  • Irritable Bowel Syndrome / metabolism
  • Irritable Bowel Syndrome / microbiology*
  • Irritable Bowel Syndrome / physiopathology
  • Male
  • Mice
  • Permeability
  • Saccharomyces boulardii*
  • TRPV Cation Channels / metabolism

Substances

  • Indoleacetic Acids
  • TRPV Cation Channels
  • TRPV1 protein, mouse
  • indoleacetic acid

Grants and funding