Host-specific Gut Microbiota
Gut Immune Maturation Depends on Colonization with a Host-Specific Microbiota
Germ-free (GF) Swiss Webster (SW) mice underwent oral gavage with pooled fecal specimens from two healthy humans or with fecal/cecal contents from specific pathogen–free (SPF) SW mice. The two groups of recipient mice--mouse gut microbiota (MMb) and human gut microbiota (HMb) colonized mice--were then maintained in separate gnotobiotic isolators. To mimic age-dependent changes in the gut microbiota and the immune system, we bred mice in the isolator, naturally exposing the offspring to maternal microbes during and after birth. Immune maturation and gut microbiota composition were studied. To monitor the evolution of gut microbial communities in these previously GF mice, we pyrosequenced bar-coded, amplified bacterial 16S rDNA in fecal samples from MMb and HMb parent mice (P0) and their first (F1) and second (F2) offspring generations.
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.