Maternal Immunoglobulin A protects against the development of necrotizing enterocolitis in preterm infants

Abstract

Abstract Neonates are particularly susceptible to infection by colonizing microbes, and mammals protect their offspring via antibodies secreted into breast milk. Necrotizing Enterocolitis(NEC) is a disease of preterm infants characterized by intestinal epithelial damage and inflammation associated with the microbiota. The incidence of NEC is significantly lower in infants fed with maternal milk, though the mechanisms underlying this protective benefit are not clear. Here, we show that maternal Immunoglobulin A (IgA) is an important factor in protection against NEC. Analysis of IgA-binding within fecal samples from preterm infants indicated that breast milk was the predominant source of IgA in the first month of life and that a relative decrease in the fraction of bacteria bound by IgA is associated with the development of NEC. Sequencing of IgA-bound and unbound bacteria revealed that NEC was associated with increasing domination of the IgA unbound microbiota by Enterobacteriaceae, prior to disease onset. Further, we confirmed that IgA is critical in preventing NEC in a murine model, where we demonstrate that pups reared by IgA deficient mothers are susceptible to disease despite exposure to maternal milk. This study illustrates the importance of maternal IgA in shaping the host-microbiota relationship of preterm neonates and provides evidence that IgA is a critical factor in maternal milk necessary for the prevention of NEC.