Human Milk Glycosaminoglycans as Possible Bioactive Substances for the Breastfed Newborn

Dear Editor:

Recently the first complete characterization and quantitative evaluation of glycosaminoglycans (GAGs) in both human and bovine milk have been reported. ¹ Chondroitin sulfate and heparin represent, respectively, approximately 55% and approximately 42% of the total human milk GAGs, whereas dermatan sulfate and hyaluronic acid make up the remaining 3%. In contrast, in bovine milk, which represents the starting material for infant formulas, dermatan sulfate constituted the main component (approximately 40%). Moreover, the total amount of GAGs in bovine milk is approximately seven times lower compared with human milk (60.2 mg/L vs. 416.2 mg/L, respectively).

In a subsequent study, ² the GAG content in the milk from mothers delivering term or preterm newborns during the first month of lactation has been evaluated. A progressive decrease of GAG concentration was observed in both milks, with absolute amounts being consistently significantly higher in preterm milk. The highest values were found in colostrum (9.3 and 3.8 g/L in preterm and term milk, respectively, at Day 4 of lactation), followed by a progressive decrease up to Day 30 (4.3 and 0.4 g/L, respectively). From the above data it can be deduced that breastfed infants daily ingest consistent amounts of GAGs.

Structurally, milk GAGs are sulfated linear polysaccharides synthesized in alveolar cells of the mammary gland by the sequential action of specific glycosyl transferases. Because of the absence of specific glycosidases and sulfatases secreted in the pancreatic juice or present on the intestinal wall, we can suppose that, once ingested, human milk GAGs can reach the small intestine in intact form. ³ Accumulated evidence indicates that many microorganisms (pathogenic bacteria, viruses, and parasites) bind GAG chains of enterocytes for efficient invasion and propagation. ⁴ As a consequence, the free GAGs, acting as soluble receptor analogs, could play an important role in preventing and protecting breastfed infants from intestinal infections.

Moreover, it has been reported that breastfed newborns develop less oxidative stress than formula-fed ones. ⁵ As chondroitin sulfate (and other GAGs) are well-known antioxidant and anti-inflammatory agents that act by activating the protein kinase C/phosphoinositide 3-kinase/Akt signaling pathway able to induce antioxidant enzymes, ⁶ these macromolecules can contribute to the antioxidant properties of human milk, which are particularly important during the neonatal period. Finally, as bifidobacteria possess specific enzymes involved in the metabolism of complex carbohydrates, ⁷ we can speculate that the undigested GAGs reaching the colon may behave as prebiotics to contribute to the development of bifidogenic flora, typical of breastfed infants (studies are in progress to evaluate this possible capacity of human milk GAGs).