Maternal gut microbiome–induced IgG regulates neonatal gut microbiome and immunity

Abstract

The gut microbiome elicits antigen-specific immunoglobulin G (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 the 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 inhibits <i>Citrobacter rodentium</i> colonization and attachment to the mucosa. Enhanced neonatal immunity against oral <i>C. rodentium</i> infection was observed after maternal immunization with a gut microbiome-derived IgG antigen, outer membrane protein A, or induction of IgG-inducing gut bacteria. Furthermore, by generating a gene-targeted mouse model with complete IgG deficiency, we demonstrate that IgG knockout neonates are more susceptible to <i>C. rodentium</i> infection and exhibit alterations of the gut microbiome that promote differentiation of interleukin-17A-producing γδ T cells in the intestine, which persist into adulthood and contribute to increased disease severity in a dextran sulfate sodium-induced mouse model of colitis. 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.