Arresting microbiome development limits immune system maturation and resistance to infection in mice
CELL HOST & MICROBE(2023)
摘要
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 devel-opment remain poorly understood. We find that restricting microbiome maturation during weaning stunts im-mune 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 pe-ripheral 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.
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