Early-Life Microbial Restitution Reduces Colitis Risk Promoted by Antibiotic-Induced Gut Dysbiosis in Interleukin 10-/- Mice.
Gastroenterology
; 161(3): 940-952.e15, 2021 09.
Article
in En
| MEDLINE
| ID: mdl-34111469
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.Key words
Full text:
1
Database:
MEDLINE
Main subject:
Bacteroides
/
Interleukin-10
/
Colitis
/
Colon
/
Gastrointestinal Microbiome
Type of study:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Animals
Language:
En
Journal:
Gastroenterology
Year:
2021
Type:
Article
Affiliation country:
Japan