Mechanisms by which maternal antibodies regulate immune responses to the microbiota in early life.

Colonization of the infant gut by commensal bacteria profoundly influences immune development and can thus have significant long-term consequences: promoting durable tolerance to environmental antigens or driving Inflammatory Bowel Disease (IBD). Despite the importance of this process for health, how immune responses to the microbiota are regulated during early life remain a significant gap in our knowledge. We discovered that antibodies targeting gut bacteria are transmitted from mother to offspring via breastfeeding where they restrain neonatal immune responses to beneficial gut bacteria. Antibodies are specialized immune proteins that bind to foreign particles, including harmful and helpful microbes. Healthy humans and mice produce distinct flavors, or “isotypes,” of antibodies that serve different functions in immunity. We revealed that the maternal antibody isotype required to restrain neonatal inflammatory responses is IgG, an isotype that has only recently been identified to participate in gut health. Human breastmilk also contains IgG, and a key role for maternal antibodies in dampening gut inflammatory responses has been described in breastfed humans. Here, we will combine new mouse models with cutting-edge approaches to define the mechanisms by which breastmilk antibodies instruct the neonate to avoid harmful responses to beneficial gut bacteria. This work will advance our ability to manipulate immune responses to gut bacteria and thus aid in the development of therapies to effectively curb the development or severity of IBD.