Human milk glycoconjugates that inhibit pathogens
Newburg, D.S.
Current Medicinal Chemistry 6(2): 117-127
1999
ISSN/ISBN: 0929-8673 PMID: 9927761 Document Number: 511175
Breast-fed infants have lower incidence of diarrhoea, respiratory disease and otitis media than formulae-fed infants. The protection by human milk has been attributed to the presence of secretory IgA. However, human milk also contains complex carbohydrates, including glycoproteins, glycolipids, glycosaminoglycans, mucins and especially oligosaccharides. Complex carbohydrate moieties of glycoconjugates and oligosaccharides are synthesized by the many glycosyltransferases in the mammary gland; those with homology to cell surface glycoconjugate pathogen receptors may inhibit pathogen binding, thereby protecting the breast-fed infant. Several examples are reviewed. A fucosyloligosaccharide inhibits the effect of stable toxin of Escherichia coli. A different fucosyloligosaccharide inhibits infection by Campylobacter jejuni. Binding of Streptococcus pneumoniae and of enteropathogenic E. coli to their respective receptors is inhibited by human milk oligosaccharides. The 46-kDa glycoprotein, lactadherin, inhibits rotavirus binding and infectivity. Low levels of lactadherin in human milk are associated with a higher incidence of symptomatic rotavirus in breast-fed infants. A mannosylated glycopeptide inhibits binding by enterohaemorrhagic E. coli. A glycosaminoglycan inhibits binding of gp120 to CD4, the first step in human immunodeficiency virus infection. Human milk mucin inhibits binding by S-fimbriated E. coli. The ganglioside, GM1, reduces diarrhoea production by cholera toxin and labile toxin of E. coli. The neutral glycosphingolipid, Gb3, binds to Shiga toxin. Thus, many complex carbohydrates of human milk may be novel antipathogenic agents, and the milk glycoconjugates and oligosaccharides may be a major source of protection for breast-fed infants.