Early-life microbial restitution reduces colitis risk promoted by antibiotic-induced gut dysbiosis in IL-10-/- mice.

Abstract

BACKGROUND & AIMS\nPerturbations in the early life gut microbiome are associated with increased risk for complex immune disorders like inflammatory bowel diseases. We previously showed maternal antibiotic-induced gut dysbiosis vertically transmitted to offspring increases experimental colitis risk in IL-10 gene deficient (IL-10-/-) mice, a finding that may result from the loss/lack of essential microbes needed for appropriate immunological 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.\n\n\nMETHODS\nMetagenomic sequencing followed by reconstruction of metagenome-assembled genomes (MAGs) was performed on fecal samples of IL-10-/- mice with and without antibiotic-induced dysbiosis to identify potential missing microbial members needed for immunological education. One high value target strain was then engrafted early and/or late into the gut microbiomes of IL-10-/- mice with antibiotic-induced dysbiosis.\n\n\nRESULTS\nEarly, but not late life engraftment of a single dominant Bacteroides strain of non-antibiotic treated IL-10-/- mice was sufficient to restore the development of the gut microbiome, promote immune tolerance, and prevent colitis in IL-10-/- mice that had antibiotic-induced dysbiosis.\n\n\nCONCLUSION\nRestitution 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.