Human milk glycosaminoglycans: the state of the art and future perspectives
© Coppa et al.; licensee BioMed Central Ltd. 2013
Received: 7 January 2013
Accepted: 10 January 2013
Published: 15 January 2013
Recently, a complete characterization and detailed evaluation of the glycosaminoglycans of human milk were performed. The total glycosaminoglycans content in milk from healthy mothers having delivered term or preterm newborns showed a constant pattern which was essentially composed of two main polysaccharides: chondroitin sulfate (60-70%) and heparin (30-40%). Moreover, considerable variations of glycosaminoglycans concentration were found during the first month of lactation, the highest values being present in colostrum compared to mature milk. Metabolism and potential biological functions of human milk glycosaminoglycans are hypothesized and future studies are encouraged.
In the last few decades consistent evidence has been reported on several human milk glycans (such as glycoproteins, glycolipids and especially oligosaccharides) which have been demonstrated to possess specific biological properties, positively influencing the breastfed newborn health [1–4]. On the contrary, only four studies are actually available in the literature on another family of complex carbohydrates, the glycosaminoglycans (GAGs) [5–8].
GAGs are linear heteropolysaccharides composed of a variable number of repeating disaccharidic units, which are able to regulate many cellular events and physiological processes (such as cell growth and differentiation, cell-cell and cell-matrix interaction, anti-infective and anti-inflammatory processes, etc.) [9–11]. On the basis of their structure and composition, GAGs are generally grouped into four main categories: 1) hyaluronic acid (HA); 2) chondroitin sulfates (CS) and dermatan sulfate (DS); (3) heparan sulfate (HS) and heparin (Hep); 4) keratan sulfate (KS).
State of the art
The first data reported in the literature on milk GAGs are those described by Shimizu et al. . Their study was not performed on whole milk but exclusively focused on milk fat globule membranes. The total GAG content was 5–10 times higher in human than in bovine milk membranes. Qualitative analyses on membranes from mature milk samples demonstrated that the major GAG in both bovine and human milk was HS (70%), with the remainder 30% represented by CS.
Further information on human milk GAG composition was later provided by the study done by Newburg et al. . Even if no quantitative data were reported, it was interestingly shown that GAGs isolated from human milk were able to play an important role as anti-infective agents.
GAGs quantitative evaluation in human and bovine milk
Total GAGs (mg/L)
Metabolism and potential biological functions
At the same level of the small intestine, the GAGs, due to their well-known properties, could contribute to the antioxidant effect of human milk, which is particularly important during the neonatal period. In fact, it has been demonstrated that CS (and other GAGs) are able to stimulate the pathway which induces the activation of antioxidant enzymes , and which is particularly important in preterm infants endowed with an immature defence system.
Furthermore, the undigested GAGs, reaching the colon, could behave as prebiotics, contributing to the development of bifidogenic flora as it has been demonstrated that bifidobacteria possess specific enzymes involved in the metabolism of carbohydrates .
Finally, a certain amount of undigested GAGs could be present in infant feces behaving as dietary fibers according to international definition.
From the review of the literature, it clearly emerges that further studies are necessary to explore the metabolic fate, the physiological role and other human milk GAGs possible positive effects on the newborn’s health. As for other glycan components such as oligosaccharides, further in vitro and in vivo studies should be performed to achieve more information on their possible antinfective, antioxidant and prebiotic effects.
Finally, new knowledge on human milk components is the starting basis for the preparation of improved infant formulas in the future.
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