The gut microbiota induces Peyer’s-patch-dependent secretion of maternal IgA into milk

The evolutionary strategy of transferring maternal antibodies via milk profoundly impacts the survival, lifelong health, and wellbeing of all neonates, including a pronounced impact on human breastfeeding success and infant development. While there has been increased recognition that interorgan connectivity influences the quality of a mother’s milk, potentially to personalize it for her offspring, the underlying bases for these processes are incompletely resolved. Here, we define an essential role of Peyer’s patches (PPs) for the generation of plasma cells that secrete maternal immunoglobulin A (IgA) into milk. Our metagenomic analysis reveals that the presence of certain residential microorganisms in the gastrointestinal (GI) tract, such as Bacteroides acidifaciens and Prevotella buccalis, is indispensable for the programming of maternal IgA synthesis prior to lactational transfer. Our data provide important insights into how the microbiome of the maternal GI environment, specifically through PPs, can be communicated to the next generation via milk. [Display omitted] •Peyer’s patches (PPs) play a key role in producing maternal IgA in milk•Antigen sampling by M cells in PPs is important for maternal IgA production in milk•The gut microbiota is involved in the appearance of maternal IgA in milk•Maternal IgA production in milk is promoted by the microbiota-PP-mammary gland pathway Usami et al. show that Peyer’s patches (PPs), a secondary lymphoid tissue in the small intestine, are involved in producing maternal IgA in milk. Bacteroides acidifaciens and Prevotella buccalis, which are intestinal residential microorganisms, play important roles in the microbiota-PP-mammary gland pathway to promote maternal IgA synthesis in milk.