Early-Life Microbial Restitution Reduces Colitis Risk Promoted by Antibiotic-Induced Gut Dysbiosis in Interleukin 10 -/- Mice

Gastroenterology. 2021 Sep;161(3):940-952.e15. doi: 10.1053/j.gastro.2021.05.054. Epub 2021 Jun 7.

Abstract

Background & aims: Perturbations in the early-life gut microbiome are associated with increased risk for complex immune disorders like inflammatory bowel diseases. We previously showed that maternal antibiotic-induced gut dysbiosis vertically transmitted to offspring increases experimental colitis risk in interleukin (IL) 10 gene deficient (IL10-/-) mice, a finding that may result from the loss/lack of essential microbes needed for appropriate immunologic education early in life. Here, we aimed to identify key microbes required for proper development of the early-life gut microbiome that decrease colitis risk in genetically susceptible animals.

Methods: Metagenomic sequencing followed by reconstruction of metagenome-assembled genomes was performed on fecal samples of IL10-/- mice with and without antibiotic-induced dysbiosis to identify potential missing microbial members needed for immunologic education. One high-value target strain was then engrafted early and/or late into the gut microbiomes of IL10-/- mice with antibiotic-induced dysbiosis.

Results: Early-, but not late-, life engraftment of a single dominant Bacteroides strain of non-antibiotic-treated IL10-/- mice was sufficient to restore the development of the gut microbiome, promote immune tolerance, and prevent colitis in IL10-/- mice that had antibiotic-induced dysbiosis.

Conclusions: Restitution of a keystone microbial strain missing in the early-life antibiotic-induced gut dysbiosis results in recovery of the microbiome, proper development of immune tolerance, and reduced risk for colitis in genetically prone hosts.

Keywords: Dysbiosis; Immune Tolerance; Inflammatory Bowel Diseases; Keystone Microbes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents
  • Bacteroides / growth & development*
  • Bacteroides / immunology
  • Colitis / immunology
  • Colitis / metabolism
  • Colitis / microbiology
  • Colitis / prevention & control*
  • Colon / immunology
  • Colon / metabolism
  • Colon / microbiology*
  • Colon / pathology
  • Disease Models, Animal
  • Dysbiosis
  • Feces / microbiology
  • Gastrointestinal Microbiome / drug effects*
  • Host-Pathogen Interactions
  • Immune Tolerance
  • Interleukin-10 / deficiency*
  • Interleukin-10 / genetics
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Proof of Concept Study
  • Time Factors

Substances

  • Anti-Bacterial Agents
  • IL10 protein, mouse
  • Interleukin-10