Prenatal antibiotics reduce breast milk IgA and induce dysbiosis in mouse offspring, increasing neonatal susceptibility to bacterial sepsis

: Antibiotics (Abx) are administered to 20%-30% of pregnant women, but their effects on neonatal immune development are poorly understood. We show that newborn mice born to Abx-treated dams are more susceptible to late-onset sepsis. This susceptibility is linked to lower maternal breast milk immunoglobulin A (IgA), neonatal fecal IgA, and IgA coating of intestinal bacteria, thus causing the translocation of intestinal pathobionts. Weaned young adults born to Abx-treated mothers had reduced IgA+ plasma cells in the ileum and colon, fecal secretory IgA (SIgA), colonic CD4+ T regulatory lymphocytes and T helper 17-like lymphocytes, and a less diverse fecal microbiome. However, treatment with apyrase, which restores SIgA secretion, prompted IgA production in breast milk and protected pups from sepsis. Additionally, breast milk from untreated mothers rescued the phenotypes of pups born to Abx-treated mothers. Our data highlight the impact of prenatal Abx on breast milk IgA and their long-term influence on intestinal mucosal immune function mediated by breastfeeding.