Protective properties of human milk. (2003)

Human breast milk is an undeniably unique, natural source of nutrition for the human infant. However, in addition to the nutritive value it imparts, breast milk and breast-feeding are well recognized to protect against gastrointestinal infections, diarrheal diseases, and respiratory infections. Such protective effects have been variously ascribed to the presence in milk of maternal leukocytes, immunoglobulins, growth factors, and immune factors. While some of these components interact directly with bacterial cells, others mediate their effects by promoting proliferation, maturation, and activation of neonatal cells and by ensuring homeostasis. The net result is an enhanced protection of the immature intestine against colonization and invasion by pathogenic bacteria. Much of the immunologic benefi t of breast milk previously described in reviews of the subject has been attributed to the passive protection that it provides. It is apparent that although breast milk supplies a combination of protective factors, functional redundancy is not rare. Not only do several factors exhibit the same biological function, a single molecule can have a range of biological activities. This complexity and the change in the concentration of specifi c components as lactation proceeds are testimony to a dynamic biological fl uid, the complete function of which has still to be fully appreciated. Indeed, there is now evidence to suggest that protective effects of breast milk extend beyond the neonatal period and can infl uence the development of pathologic diseases later in life. This is further support for a more intimate association between the maternally derived milk factors and the neonatal immune system beyond that required to prevent pathogen colonization and infection. The mechanisms underlying the long-lasting benefi ts of breast milk are likely to be multifarious. However, at least two different and partially overlapping processes are probably involved. First, breast milk factors, in shaping the composition of the neonatal microbiota, indirectly infl uence immune system development and response. Second, breast milk directly “educates” the neonatal immune system to react with appropriate innate or adaptive immune responses upon microbial and antigenic challenge. Indeed, there is increasing evidence to suggest that upon exposure to antigen, breast milk educates the neonatal immune system in the decisions to be made. Breast milk contains a myriad of factors that, qualitatively or quantitatively, may modulate how neonatal cells perceive microbial components or respond to microbes with which they come in contact. Examples are immunoglobulins, glycoproteins, and glycolipids, which interfere with bacterial binding to epithelial cells, and oligosaccharides and antimicrobial peptides, which encourage the preponderance of particular microbial species. It has also been suggested that the latter is achieved via breast milk–derived bacteria that ultimately colonize the neonatal gut. However, an emerging concept is that breast milk infl uences the neonatal immune system’s perception of “danger.” To do so, some milk molecules may actually facilitate the intestinal response to specifi c microbial motifs by activating intracellular signaling pathways such as that of nuclear factor (NF)-κB, a major regulator of the infl ammatory response. At fi rst, this might appear to contradict the recognized anti-inflammatory effect of breast milk. However, the present chapter will elaborate further on breast milk factors that modulate the neonate’s perception of danger signals in the absence of exaggerated infl ammation. More specifi cally, it will address those factors that promote a benefi cial microbial fl ora either directly or indirectly via education of neonatal cells. Moreover, it will challenge the theory that milk is strictly anti-infl ammatory by proposing novel mechanisms by which the mother already educates her infant in the immediate postnatal period.