Milk IgA promotes symbionts and limits pathobionts in the early life gut

Abstract Secretory Immunoglobulin A (SIgA) is the dominant mucosal antibody and a key regulator of the gut microbiota. In early life, infants rely on breastmilk as their primary source of SIgA, but the role of milk-derived SIgA in early life microbiota colonization dynamics remains incompletely understood. Here, we show that species-specific SIgA in milk is antigen-inducible and discriminates between closely related but immunologically diverging microbes in the neonatal gut. More specifically, milk species-specific SIgA promotes colonization by an anti-inflammatory Escherichia coli strain while restricting the expansion of pro-inflammatory Proteus mirabilis. These findings uncover a dual role of maternal milk SIgA in actively sculpting the early life gut microbiota with species-level precision.