Neonatal gut microbiota succession in mice mapped over time, site, injury and single immunoglobulin interleukin-1 related receptor genotype

Microbial succession during postnatal gut development in mice is likely impacted by site of sampling, time, intestinal injury, and host genetics. We investigated this in wild-type and <i>Sigirr</i> transgenic mice that encode the p.Y168X mutation identified in a neonate with necrotizing enterocolitis (NEC). Temporal profiling of the ileal and colonic microbiome after birth to weaning revealed a clear pattern of progression from a less diverse, Proteobacteria/Escherichia_Shigella dominant community to a more diverse, Firmicutes/Bacteroidetes dominant community. Formula milk feeding, a risk factor for necrotizing enterocolitis, decreased Firmicutes and increased Proteobacteria leading to enrichment of bacterial genes denoting exaggerated glycolysis and increased production of acetate and lactate. <i>Sigirr</i> transgenic mice exhibited modest baseline differences in microbiota composition but exaggerated formula feeding-induced dysbiosis, mucosal inflammation, and villus injury. Postnatal intestinal microbiota succession in mice resembles human neonates and is shaped by developmental maturity, ileal vs. colonic sampling, formula feeding, and <i>Sigirr</i> genotype.