Arresting microbiome development limits immune system maturation and resistance to infection in mice

Disruptions to the intestinal microbiome during weaning lead to negative effects on host immune function. However, the critical host-microbe interactions during weaning that are required for immune system development remain poorly understood. We find that restricting microbiome maturation during weaning stunts immune system development and increases susceptibility to enteric infection. We developed a gnotobiotic mouse model of the early-life microbiome Pediatric Community (PedsCom). These mice develop fewer peripheral regulatory T cells and less IgA, hallmarks of microbiota-driven immune system development. Furthermore, adult PedsCom mice retain high susceptibility to Salmonella infection, which is characteristic of young mice and children. Altogether, our work illustrates how the post-weaning transition in microbiome composition contributes to normal immune maturation and protection from infection. Accurate modeling of the pre-weaning microbiome provides a window into the microbial requirements for healthy development and suggests an opportunity to design microbial interventions at weaning to improve immune development in human infants. [Display omitted] •A bacterial consortium is developed to model the murine pre-weaning intestinal microbiome•Restricted intestinal microbiome maturation leads to stunted immune system development•Restricted microbiome development increases susceptibility to Salmonella infection The transition from a pre-weaning intestinal microbiome to an adult-like community is a critical period in host development. Lubin et al. explore the consequences of restricting the intestinal microbiome to a pre-weaning configuration on normal immune system maturation, major microbially derived metabolite generation, and susceptibility to enteric infection.