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This Article Full Text (PDF) All Versions of this Article: jas.2008-1347v1 87/13_suppl/26    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Newburg, D. S. Search for Related Content PubMed PubMed Citation Articles by Newburg, D. S.

Neonatal protection by an innate immune system of human milk consisting of oligosaccharides and glycans

Division of Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital for Children and Harvard Medical School, Boston 02129

dnewburg{at}partners.org

Abstract

This review discusses the role of human milk glycans in protecting infants, but the conclusion that the human milk glycans comprise an innate immune system whereby the mother protects her offspring may have general applicability in all mammals, including species of commercial importance. Infants that are not breastfed have a higher incidence of severe diarrhea and respiratory diseases than those that are breastfed. In the past, this had been attributed primarily to human milk secretory antibodies. However, the oligosaccharides are major components of human milk, and milk is also rich in other glycans, including glycoproteins, mucins, glycosaminoglycans, and glycolipids. These milk glycans, especially the oligosaccharides, are comprised of thousands of components. The milk factor that promotes gut colonization by Bifidobacterium bifidum was found to be a glycan, and such prebiotic characteristics may contribute to protection against infectious agents. However, the ability of human milk glycans to protect the neonate seems primarily to be due to their inhibition of pathogen binding to their host cell target ligands. Many such examples include specific fucosylated oligosaccharides and glycans that inhibit specific pathogens. Most human milk oligosaccharides are fucosylated, and their production depends on fucosyltransferase enzymes; mutations in these fucosyltransferase genes are common, and underlie the various Lewis blood types in humans. Variable expression of specific fucosylated oligosaccharides in milk, also a function of these genes (and maternal Lewis blood type), is significantly associated with the risk of infectious disease in breastfed infants. Human milk also contains major quantities and large numbers of sialylated oligosaccharides, many of which are also present in bovine colostrum. These could similarly inhibit several common viral pathogens. Moreover, human milk oligosaccharides strongly attenuate inflammatory processes in the intestinal mucosa. These results support the hypothesis that oligosaccharides and other glycans are the major constituents of an innate immune system of human milk whereby the mother protects her infant from enteric and other pathogens through breastfeeding. These protective glycans may prove useful as a basis for the development of novel prophylactic and therapeutic agents that inhibit disease by mucosal pathogens in many species.

Key Words: Glycans • human milk • innate immunity • oligosaccharides