Gut Immune Maturation Depends on Colonization with a Host-Specific Microbiota

Gut microbial induction of host immune maturation exemplifies host-microbe mutualism. We colonized germ-free (GF) mice with a mouse microbiota (MMb) or a human microbiota (HMb) to determine whether small-intestinal immune maturation depends on a coevolved host-specific microbiota. Gut bacterial numbers and phylum abundance were similar in MMb and HMb mice, but bacterial species differed, especially the Firmicutes. HMb mouse intestines had low levels of CD4+ and CD8+ T cells, few proliferating T cells, few dendritic cells, and low antimicrobial peptide expression—all characteristics of GF mice. A rat microbiota also failed to fully expand intestinal T-cell numbers in mice. Colonizing GF or HMb mice with mouse segmented filamentous bacteria (SFB) partially restored T-cell numbers, suggesting that SFB and other MMb organisms are required for full immune maturation in mice. Importantly, MMb conferred better protection against Salmonella infection than HMb. A host-specific microbiota appears to be critical for a healthy immune system.