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

Jean Bernard Lubin, Jamal Green, Sarah Maddux, Lidiya Denu, Tereza Duranova, Matthew Lanza, Meghan Wynosky-Dolfi, Julia N. Flores, Logan P. Grimes, Igor E. Brodsky, Paul J. Planet, Michael A. Silverman

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)554-570.e7
JournalCell Host and Microbe
Volume31
Issue number4
DOIs
StatePublished - Apr 12 2023

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Virology

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