Gut microbiome and breast-feeding: Implications for early immune development.

Establishment of the gut microbiome during early life is a complex process with lasting implications for an individual's health. Several factors influence microbial assembly; however, breast-feeding is recognized as one of the most influential drivers of gut microbiome composition during infancy, with potential implications for function. Differences in gut microbial communities between breast-fed and formula-fed infants have been consistently observed and are hypothesized to partially mediate the relationships between breast-feeding and decreased risk for numerous communicable and noncommunicable diseases in early life. Despite decades of research on the gut microbiome of breast-fed infants, there are large scientific gaps in understanding how human milk has evolved to support microbial and immune development. This review will summarize the evidence on how breast-feeding broadly affects the composition and function of the early-life gut microbiome and discuss mechanisms by which specific human milk components shape intestinal bacterial colonization, succession, and function.

Effects of Milk Secretory Immunoglobulin A on the Commensal Microbiota.

Secretory immunoglobulin A (SIgA) is intimately involved in the transfer of maternal immunity to the newborn breastfed infant. Recent research demonstrates the significance of SIgA in the initial development of the newborn's microbiota and in the establishment of a tolerogenic immunologic disposition towards nonpathogenic organisms and environmental antigens. SIgA has long been known to prevent pathogen binding to the host epithelium through immune exclusion involving numerous mechanisms. This process primarily involves T-cell-dependent, somatically hypermutated monoclonal antibodies with high specificity towards pathogen surface antigens, and the success of the immune response is dependent upon the specific antigen recognition. Whereas this role is important, there is an alternate, dual role for SIgA in the health of the host - protection and promotion of commensal colonization and maintenance of homeostatic immunity. This latter role is primarily dependent upon N- and O-glycan moieties lining the secretory component and heavy chain of the SIgA dimer, with interactions independent of immunoglobulin specificity. These SIgA molecules are nonspecific polyclonal antibodies generated from plasma cells activated by dendritic cell sampling of luminal contents in the absence of inflammation. Breast milk is the primary supply of such polyclonal polyreactive SIgA in the initial stages of neonatal colonization, and it provides vital pathogen resistance while promoting colonization of commensal microbiota.

Mother's Touch: Milk IgA and Protection from Necrotizing Enterocolitis.

Human milk feeding is associated with lower rates of necrotizing enterocolitis (NEC), but an understanding of mechanism is lacking. In recent work, Gopalakrishna et al. report that human infants who develop NEC first experience an increase in Enterobacteriaceae in the portion of the microbiota not bound to IgA.