Gut Microbiota Composition Imprints Optimal Humoral Immunity

The infant immune system co-evolves with the developing gut microbiota in a mutualistic relationship, providing signals that imprint immune health for life. Recent studies have demonstrated the immunomodulatory effects microbiota exert on humoral immune development using germ-free mice and antibiotic treatment. However, examining the impact that naturally divergent gut microbial communities have on the development of humoral immunity remains to be elucidated.

We have developed a model system whereby two lines of BALB/c mice harbour naturally divergent gut microbiota, resulting in a prominent difference in the Firmicutes to Bacteroidetes ratio. These two lines of mice demonstrate disparate levels of immune activation, resulting in markedly different antibody responses. In turn, protective immunity to infectious disease and susceptibility to allergic disease is affected. Microbiota transfer in early life is able to alter the antibody phenotype in both lines of BALB/c mice; demonstrating microbial composition imprints the capability of the humoral response throughout life. Taken together, we have established a critical window during the ontogeny of the immune system in which gut microbial composition may be therapeutically manipulated to promote optimal humoral immunity.