Human milk glycosaminoglycans: the state of the art and future perspectives (original) (raw)
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Composition and structure elucidation of human milk glycosaminoglycans
Glycobiology, 2011
To date, there is no complete structural characterization of human milk glycosaminoglycans (GAGs) available nor do any data exist on their composition in bovine milk. Total GAGs were determined on extracts from human and bovine milk. Samples were subjected to digestion with specific enzymes, treated with nitrous acid, and analyzed by agarose-gel electrophoresis and high-performance liquid chromatography for their structural characterization. Quantitative analyses yielded 7 times more GAGs in human milk than in bovine milk. In particular, galactosaminoglycans, chondroitin sulfate (CS) and dermatan sulfate (DS), were found to differ considerably from one type of milk to the other. In fact, hardly any DS was observed in human milk, but a low-sulfated CS having a very low charge density of 0.36 was found. On the contrary, bovine milk galactosaminoglycans were demonstrated to be composed of 66% DS and 34% CS for a total charge density of 0.94. Structural analysis performed by heparinases showed a prevalence of fast-moving heparin over heparan sulfate, accounting for 30-40% of total GAGs in both milk samples and showing lower sulfation in human (2.03) compared with bovine (2.28). Hyaluronic acid was found in minor amounts. This study offers the first full characterization of the GAGs in human milk, providing useful data to gain a better understanding of their physiological role, as well as of their fundamental contribution to the health of the newborn.
Human milk glycosaminoglycan composition from women of different countries: a pilot study
The Journal of Maternal-Fetal & Neonatal Medicine, 2019
Objective: In this pilot study we report the composition, structure and properties of glycosaminoglycans present in milk samples of various countries and ethnicities. Methods:50 samples of human milk were analysed, 10 from East Europe, 10 from North Africa, 10 from Central Africa, 10 from South America and 10 from Asia. Moreover, 30 samples were obtained during the first week and 20 between 8 to 30 days of life. Results: Overall, no significant differences were observed for the qualitative composition of GAGs, mainly chondroitin sulfate, heparan sulfate and hyaluronic acid, comparing the mothers from the various countries and between the 30 milks obtained during the first week and the 20 samples collected thereafter. Moreover, no significant differences in human milk GAGs within the different groups analysed belonging to various counties and ethnicities were observed. Conclusions:These results may be of useful, as in the case of pilot studies with infant formulas enriched with CS and/or HS necessary to verify their possible positive effects on newborns feeding in countries at high risk of infection and/or infestation.
Glycosaminoglycan Content in Term and Preterm Milk during the First Month of Lactation
Neonatology, 2012
Italy (Prof. Bertino MD). Contributors N.V. developed the applied methodologies. L.Z., T.G., F.M., D.B. and F.B. performed the experimental procedures and analyses. E.B. contributed in milk sample collection. N.V., G.V.C. and O.G. designed and developed the experimental design, performed data analysis and wrote the manuscript. All authors reviewed and approved the study. Conflicts of interest We declare that we have no conflicts of interest.
Effect of Holder Pasteurisation on Human Milk Glycosaminoglycans
Journal of Pediatric Gastroenterology and Nutrition, 2015
Objectives: The benefits of human milk for preterm infants are mainly the result of its nutritional characteristics and the presence of biologically active compounds. Among these compounds, glycosaminoglycans (GAGs) play an emerging leading role. When mother's milk is unavailable or in short supply, pasteurised donor milk represents an important nutritional alternative. The aim of this study was to evaluate the effect of Holder pasteurisation on the concentration of different GAGs in preterm human milk. Methods: Milk samples collected from 9 mothers having delivered preterm were divided into 2 parts. One part of each sample was immediately frozen (À808C), whereas the other part was pasteurised with the Holder method before being frozen at À808C. Specific analytical procedures were applied to evaluate the amount, composition, and structure of main human milk GAGs. Results: No significative differences were measured between not-treated and pasteurised samples for total GAGs content, relative percentages of chondroitin sulfate and heparan sulfate, and main parameters related to galactosaminoglycans structure, even if a slight decrease of total GAGs content of $18% was observed in treated samples.
Breastfeeding Medicine, 2014
M uch evidence has been obtained that several human milk glycans (glycoproteins, glycolipids, and especially oligosaccharides), behaving as cell surface receptor homologs, are able to inhibit binding of pathogens and thus protect the newborn against several enteric infections. 1 Moreover, recent studies have focused attention on human milk complex sulfated polysaccharides, the glycosaminoglycans (GAGs), as well as their structure and their possible biological roles. 2,3 However, no data are yet available regarding the metabolic fate of GAGs and their possible presence in the feces of breastfed newborns or regarding their composition and structure, which would be useful to shed light on their metabolism.
HUMAN MILK GLYCANS PROTECT INFANTS AGAINST ENTERIC PATHOGENS
Annual Review of Nutrition, 2005
Breastfed infants have lower morbidity and mortality due to diarrhea than those fed artificially. This had been attributed primarily to the secretory antibodies and prebiotic factors in human milk. Oligosaccharides are the third largest component of human milk. They were initially considered to be functionless by-products of glycoprotein and glycolipid synthesis during milk production. However, in the past few decades it has become apparent that the human milk oligosaccharides are composed of thousands of components, at least some of which protect against pathogens. Oligosaccharide protection against infectious agents may result in part from their prebiotic characteristics, but is thought to be primarily due to their inhibition of pathogen binding to host cell ligands. Most human milk oligosaccharides are fucosylated, and their production depends on enzymes encoded by the genes associated with expression of the Lewis blood group system. The expression of specific fucosylated oligosaccharides in milk thus varies in relation to maternal Lewis blood group type, and is significantly associated with the risk of infectious disease in breastfed infants. Specific fucosylated moieties of oligosaccharides and related glycoconjugates (glycans) are able to inhibit binding and disease by specific pathogens. This review presents the argument that specific glycans, especially the oligosaccharides, are the major constituent of an innate immune system of human milk whereby the mother protects her infant from enteric and other pathogens through breastfeeding. The large input of energy expended by the mother in the synthesis of milk oligosaccharides is consistent with the human reproductive strategy of large parental input into rearing relatively few offspring through a prolonged period of maturation. These protective glycans may prove useful as a basis for the development of novel prophylactic and therapeutic agents that inhibit diseases caused by mucosal pathogens.
O-Glycosylation of α-1-Acid Glycoprotein of Human Milk Is Lactation Stage Related
Breastfeeding Medicine, 2015
Background: Human milk provides a multitude of glycoproteins, including highly glycosylated a-1-acid glycoprotein (AGP), which elicits anti-inflammatory and immunomodulatory properties. The milk AGP glycoforms may provide the breastfed infant with a wide range of biological benefits. Here, we analyzed the reactivity of O-linked sugar-specific lectins with human milk AGP over the process of lactation and compared the results with those of the lactating mother's plasma. Materials and Methods: Relative amounts of human skim milk AGP O-glycans were analyzed in early colostrum, colostrum, and transitional and mature milk samples of 127 healthy mothers by lectin-AGP enzymelinked immunosorbent assay using sialyl T (sialyl-a2,3/a2,6 Galb1,3GalNAc-), asialyl T (Galb1,3GalNAc-), and Tn (GalNAc-) antigen-specific biotinylated Artocarpus integrifolia ( Jacalin), Arachis hypogaea (PNA), and Vicia villosa (VVA) lectins, respectively. Results: Milk AGP elicited high expression of Jacalin-and PNA-reactive glycotopes and low expression of VVA-reactive glycotopes, which were absent on plasma AGP of lactating mothers and healthy individuals. The expression of sialyl, asialyl T, and Tn glycotopes of human milk AGP was lactation stage related. The relative amount of Jacalin-reactive AGP glycotope was highest in the colostrum samples and then decreased starting from Day 8 of lactation. In contrast, an increase of the relative amount of PNA-reactive glycotope with milk maturation was observed. The relative amount of VVA-reactive glycotope remained almost constant over the development of lactation. Conclusions: Milk AGP differs from mother's plasma AGP by the presence of O-linked sialylated and asialylated T as well as Tn antigens. The variation of the expression of sialylated and asialylated T and Tn antigens on AGP is associated with milk maturation.
Breast milk oligosaccharides: structure-function relationships in the neonate
Annual review of nutrition, 2014
In addition to providing complete postnatal nutrition, breast milk is a complex biofluid that delivers bioactive components for the growth and development of the intestinal and immune systems. Lactation is a unique opportunity to understand the role of diet in shaping the intestinal environment including the infant microbiome. Of considerable interest is the diversity and abundance of milk glycans that are energetically costly for the mammary gland to produce yet indigestible by infants. Milk glycans comprise free oligosaccharides, glycoproteins, glycopeptides, and glycolipids. Emerging technological advances are enabling more comprehensive, sensitive, and rapid analyses of these different classes of milk glycans. Understanding the impact of inter- and intraindividual glycan diversity on function is an important step toward interventions aimed at improving health and preventing disease. This review discusses the state of technology for glycan analysis and how specific structure-func...