Perturbation of mammary immunoglobulins during maternal antibiotic administration

The National Institute of Allergy and Infectious Diseases awarded $836,132 to Magee-Womens Research Institute and Foundation on June 17, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to investigate how maternal antibiotic exposure disrupts immunoglobulins in breast milk and impacts neonatal immunity.

The research addresses the mechanisms by which antibiotics prescribed during pregnancy—used in up to 40 percent of pregnancies—affect secretory immunoglobulin A (sIgA) in milk, an essential component of neonatal mucosal immunity that shapes early gut microbial colonization and protects against enteric pathogens. Preliminary data suggest that maternal antibiotic exposure disrupts the gut-to-mammary immune cell trafficking pathway, reducing pathogen-reactive IgA in milk and potentially increasing neonatal infection susceptibility, including late-onset sepsis and necrotizing enterocolitis. The project will determine the magnitude and duration of antibiotic-induced changes in milk antibodies, map the underlying mechanisms affecting immune cell recruitment to the mammary gland and microbial stimulation, and assess downstream effects on neonatal intestinal health.

Performance occurs at the recipient's location in Pittsburgh, Pennsylvania. The period of performance extends from the award date through May 31, 2031. The assistance type is a Project Grant, a standard NIH research funding mechanism supporting investigator-initiated biomedical research.

Abstract

Prescribed in up to 40% of pregnancies, antibiotics represent the most commonly used class of medication during pregnancy. Although this practice is often necessary for maternal health, accumulating evidence suggests that antibiotic exposure may have unintended consequences for the mother-infant dyad. Epidemiologic studies associate maternal antibiotic exposure, especially in the absence of infection, with increased risk of neonatal complications including late-onset sepsis (LOS) and necrotizing enterocolitis (NEC), yet the mechanisms driving these associations remain poorly understood. Secretory IGA (siga) in milk is an essential component of neonatal mucosal immunity, shaping early GUT microbial colonization and providing protection against enteric pathogens. The mechanisms by which maternal physiology regulates the abundance and microbial specificity of these antibodies in milk remain poorly understood. In animal models, the maternal GUT-mammary axis governs the generation of milk IGA: IGA-committed lymphocytes from the maternal intestine migrate to the mammary gland during advancing pregnancy via CCL- 28/CCR10 signaling. Our preliminary data suggest that maternal antibiotic exposure disrupts this process leading to a decrease in milk IGA. However, the timing and extent of antibody dysbiosis are undefined; the downstream effects on neonatal intestinal health are unknown; and the underlying mechanisms-whether due to altered microbial stimulation, impaired recruitment of IGA⁺ cells to the mammary gland, or both-remain to be elucidated. Our central hypothesis is that maternal antibiotic exposure reduces pathogen-reactive IGA in milk by impairing GUT-to-mammary immune cell trafficking thereby compromising neonatal mucosal immunity and increasing infection susceptibility. We will address this hypothesis through three integrated aims: (1) determine the magnitude and duration of antibiotic-mediated mammary antibody dysbiosis in women who deliver preterm and at term; (2) identify microbial targets of mammary antibodies diminished by maternal antibiotic exposure and (3 determine the role of maternal antibiotics in the disruption of mammary resident IGA+ plasma cells in animal models. This integrative human and animal study will uncover critical mechanisms by which maternal antibiotic use alters the maternal-infant immune axis. The results will provide mechanistic insight into the risks associated with perinatal antibiotic exposure and inform clinical strategies to mitigate risk to neonatal health.