Stability and heterogeneity in the antimicrobiota reactivity of human milk-derived immunoglobulin A

Immunoglobulin A (IgA) is secreted into breast milk and is critical for both protecting against enteric pathogens and shaping the infant intestinal microbiota. The efficacy of breast milk-derived maternal IgA (BrmIgA) is dependent upon its specificity; however, heterogeneity in BrmIgA binding ability to the infant microbiota is not known. Using a flow cytometric array, we analyzed the reactivity of BrmIgA against bacteria common to the infant microbiota and discovered substantial heterogeneity between all donors, independent of preterm or term delivery. Surprisingly, we also observed intradonor variability in the BrmIgA response to closely related bacterial isolates. Conversely, longitudinal analysis showed that the antibacterial BrmIgA reactivity was relatively stable through time, even between sequential infants, indicating that mammary gland IgA responses are durable. Together, our study demonstrates that the antibacterial BrmIgA reactivity displays interindividual heterogeneity but intraindividual stability. These findings have important implications for how breast milk shapes the development of the preterm infant microbiota and protects against necrotizing enterocolitis.