Maternal gut microbiome-induced IgG regulates neonatal gut microbiome and immunity: IgG-/- vs WT after DSS

The gut microbiome elicits antigen-specific IgG at steady state that cross-reacts to pathogens to confer protection against systemic infection. The role of gut microbiome-specific IgG antibodies in the development of gut microbiome and immunity against enteric pathogens in early life, however, remains largely undefined. In this study, we show that gut microbiome-induced maternal IgG is transferred to the neonatal intestine through maternal milk via the neonatal Fc receptor and directly inhibit C. rodentium colonization and attachment to the mucosa. Enhanced neonatal immunity against oral C. rodentium infection was observed following maternal immunization with a gut microbiome-derived IgG antigen, outer-membrane protein A (OMP-A), or induction of protective IgG antibodies by IgG-inducing gut bacteria. Furthermore, by generating a novel mouse model with complete IgG deficiency, we demonstrate that IgG KO neonates are more susceptible to C. rodentium infection, and exhibit alterations of the gut microbiome that promotes IL-17A- producing gd T cells in intestine, which persist into adulthood and contribute to increased disease severity in a DSS-induced colitis model. Taken together, our studies have defined a critical role for maternal gut microbiome-specific IgG antibodies in promoting immunity against enteric pathogens and shaping the development of the gut microbiome and immune cells in early life.16S rRNA sequencing was performed on colon luminal contents from 5 wildtype and 5 IgG-/- mice after one week of DSS treatment.