Glycobiology Advance Access originally published online on November 24, 2003
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Glycobiology vol 14 no 3 pp. 253-263, 2004
Glycobiology vol. 14 no. 3 © Oxford University Press 2004; all rights reserved.
Innate protection conferred by fucosylated oligosaccharides of human milk against diarrhea in breastfed infants
2 Program in Glycobiology, Shriver Center, University of Massachusetts Medical School, Waltham, MA 02452; 3 Departamento de Infectologia, Instituto Nacional de Ciencias Medicas y Nutricion, Mexico City 14000, Mexico; and 4 Center for Epidemiology and Biostatistics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229
Received on September 12, 2003; revised on September 26, 2003; accepted on October 23, 2003
To test the hypothesis that human milk fucosyloligosaccharides are part of an innate immune system, we addressed whether their expression (1) depends on maternal genotype and (2) protects breastfed infants from pathogens. Thus the relationship between maternal Lewis blood group type and milk oligosaccharide expression and between variable oligosaccharide expression and risk of diarrhea in their infants was studied in a cohort of 93 Mexican breastfeeding mother–infant pairs. Milk of the 67 Lea–b+ mothers contained more LNF-II (Lea) and 3-FL (Lex) (oligosaccharides whose fucose is exclusively 
1,3- or 1,4-linked) than milk from the 24 Lea-b- mothers; milk from Lea-b- mothers contained more LNF-I (H-1) and 2'-FL (H-2), whose fucose is exclusively 1,2-linked. The pattern of oligosaccharides varied among milk samples; in each milk sample, the pattern was summarized as a ratio of 2-linked to non-2-linked fucosyloligosaccharides. Milks with the highest ratios were produced primarily by Lea-b- mothers; those with the lowest ratios were produced exclusively by Lea–b+ mothers (p<0.001). Thus maternal genetic polymorphisms expressed as Lewis blood group types are expressed in milk as varied fucosyloligosaccharide ratios. The four infants who developed diarrhea associated with stable toxin of Escherichia coli were consuming milk with lower ratios (4.4 ± 0.8 [SE]) than the remaining infants (8.5 ± 0.8; p<0.001). Furthermore, the 27 infants who developed moderate to severe diarrhea of any cause were consuming milk with lower ratios (6.1 ± 0.9) than the 26 who remained healthy (10.5 ± 1.9; p = 0.042). Thus, milk with higher 2-linked to non-2-linked fucosyloligosaccharide ratios affords greater protection against infant diarrhea. We conclude that specific oligosaccharides constitute a major element of an innate immune system of human milk.
1 To whom correspondence should be addressed; e-mail: david.newburg{at}umassmed.edu
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