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Curr Med Chem. 1999 Feb;6(2):117-27.
Human milk glycoconjugates that inhibit
pathogens.
Newburg DS.
Shriver Center for Mental Retardation 200
Trapelo Road, Waltham, Massachusetts 02452 USA.
Breast-fed infants have lower incidence of
diarrhea, respiratory disease, and otitis media.
The protection by human milk has long been
attributed to the presence of secretory IgA.
However, human milk contains large numbers and
amounts of complex carbohydrates, including
glycoproteins, glycolipids, glycosaminoglycans,
mucins, and especially oligosaccharides. The
oligosaccharides comprise the third most
abundant solid constituent of human milk, and
contain a myriad of structures. 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 nursing infant. Several
examples are reviewed: A fucosyloligosaccharide
inhibits the diarrheagenic 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-kD 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
enterohemorrhagic E. coli. A glycosaminoglycan
inhibits binding of gp120 to CD4, the first step
in HIV infection. Human milk mucin inhibits
binding by S-fimbriated E. coli. The ganglioside,
GM1, reduces diarrhea production by cholera
toxin and labile toxin of E. coli. The neutral
glycosphingolipid, Gb3, binds to Shigatoxin.
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 breastfeeding
infants.
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