The Functional Power of the Human Milk Proteome

Abstract

Human milk is the most complete and ideal form of nutrition for the developing infant. The composition of human milk consistently changes throughout lactation to meet the changing functional needs of the infant. The human milk proteome is an essential milk component consisting of proteins, including enzymes/proteases, glycoproteins, and endogenous peptides. These compounds may contribute to the healthy development in a synergistic way by affecting growth, maturation of the immune system, from innate to adaptive immunity, and the gut. A comprehensive overview of the human milk proteome, covering all of its components, is lacking, even though numerous analyses of human milk proteins have been reported. Such data could substantially aid in our understanding of the functionality of each constituent of the proteome. This review will highlight each of the aforementioned components of human milk and emphasize the functionality of the proteome throughout lactation, including nutrient delivery and enhanced bioavailability of nutrients for growth, cognitive development, immune defense, and gut maturation.

Keywords: breastfeeding; endogenous peptide; glycoprotein; human milk; protein.

Figure 1

Physiology and transport of the proteome in a lactating mammary gland. (A) One lobulo-alveolar cluster connected to a lactiferous duct is depicted. The alveolus cluster, made up of a monolayer of polarized alveolar mammary epithelial cells (MEC) surrounding the lumen, and is connected to the lactiferous duct that is surrounded by a bilayer of ductal MEC. The alveolar MEC are surrounded by basement membrane and a single layer of polarized myoepithelial cells that contract to stimulate milk ejection from the lumen. The alveoli are embedded in a stoma of vascularized connective-tissue that contains lipid-depleted adipocytes, fibroblasts, endothelial cells and capillaries. (B) A zoomed in representation of the alveolar MEC is depicted to show the four key transport pathways of the milk proteome. Pathway (1) The exocytotic pathway is the dominant way for the secretion of endogenously generated proteins. These proteins and other aqueous components of milk are transported in secretory vesicles (SVs). Pathway (2) Secretion of lipid-associated proteins by the formation of lipid droplets (LDs), formed in the endoplasmic reticulum (ER), that move to the apical membrane to be secreted as milk fat globule (MFG). MFG are excreted by budding and are enwrapped by the apical plasma membrane of the MEC and become MFGM. Pathway (3) The vesicular transcytosis of proteins from serum or stromal cells. Pathway (4) Direct transport via the paracellular pathway for serum substances and cells, such as immune cells and stem cells. This route of transport is only available during pregnancy, early lactation prior to tight junction closure of MEC, involution, during times of inflammation or preterm birth.

Figure 2

The power of the human milk proteome stems from an evolutionary advantage of cross communication between the mother-infant dyad, via the enteromammary pathway, which in turn stimulated the rise of the uniquely functioning proteome and all of its components. These components work both individually and synergistically to provided protective immunity and overall development to the infant while maintaining health benefits for the mother as well.