Glycoconjugates in human milk: Protecting infants from disease

Abstract

Breastfeeding is known to have many health benefits for a newborn. Not only does human milk provide an excellent source of nutrition, it also contains components that protect against infection from a wide range of pathogens. Some of the protective properties of human milk can be attributed to the immunoglobulins. Yet, there is another level of defense provided by the "sweet" protective agents that human milk contains, including free oligosaccharides, glycoproteins and glycolipids. Sugar epitopes in human milk are similar to the glycan receptors that serve as pathogen adhesion sites in the human gastrointestinal tract and other epithelial cell surfaces; hence, the milk glycans can competitively bind to and remove the disease-causing microorganisms before they cause infection. The protective value of free oligosaccharides in human milk has been well researched and documented. Human milk glycoconjugates have received less attention but appear to play an equally important role. Here, we bring together the breadth of research that has focused on the protective mechanisms of human milk glycoconjugates, with a particular focus on the glycan moieties that may play a role in disease prevention. In addition, human milk glycoconjugates are compared with bovine milk glycoconjugates in terms of their health benefits for the human infant.

O-Glycosylation of α-1-Acid Glycoprotein of Human Milk Is Lactation Stage Related

“…The appearance of the O-linked T and Tn glycotopes on human milk AGP, which are not found on the free milk oligosaccharides, 15,34 can be considered in the context of evolutionary adaptation of bioactive components of human milk to act as a part of innate immunity passed down through the mother to the breastfed newborn because they can as soluble decoys participate in preventing the adhesion of viruses and bacteria to their carbohydrate mucosal receptors or in protection against bacterial and viral diseases. 3,4,9,15,35 The values of r calculated according to the Spearman method correspond to correlation between the relative amounts of glycotopes expressed on human milk a-1-acid glycoprotein (AGP) over milk maturation from Day 2 to Day 45 of lactation. Data of milk AGP reactivity with sialic acid-specific lectins (M. amurensis lectin [MAA] and S. nigra lectin [SNA]) were previously reported.…”

“…[1][2][3] Terminally located monosaccharides or some sugar sequences of both forms of milk carbohydrates are reported to take part in modulation of signaling, inflammation, inhibition of bacteria from binding to the host epithelial cells, and stimulation of growth of beneficial bacteria in the intestine (reviewed by Bode, 1 Newburg, 2 Peterson et al, 3 and Liu and Newburg 4 ). Because of the above-mentioned abilities, they are believed to be involved in maintaining infants' well-being and to protect breastfed infants from disease.…”

The Impact of the Milk Glycobiome on the Neonate Gut Microbiota

“…The majority of milk glycoproteins are found in skim milk (whey and casein), but the milk fat globule membrane (MFGM) contains a representative amount of total glycoproteins (reviewed in 13). The most abundant human milk glycoproteins are α-lactalbumin (17% of total protein), lactoferrin (Lf) (17%), and secretory IgA (sIgA) (11%), belonging to the whey fraction, and κ-casein, from casein fraction (9%) (13). …”

An Opinion on “Staging” of Infant Formula

“…Similar to fat, the lactose content is lower in the early milk than in mature milk, produced after the first weeks of lactation, but thereafter remains relatively constant (23). The milk oligosaccharides, however, exhibit pronounced changes during lactation not only in concentration but also in composition, complexity, and structure (39,40).…”