Innate protection conferred by fucosylated oligosaccharides of human milk against diarrhea in breastfed infants

Abstract

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 Le^a–b+ mothers contained more LNF-II (Le^a) and 3-FL (Le^x) (oligosaccharides whose fucose is exclusively α1,3- or α1,4-linked) than milk from the 24 Le^a−b− mothers; milk from Le^a−b− mothers contained more LNF-I (H-1) and 2′-FL (H-2), whose fucose is exclusively α1,2-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 Le^a−b− mothers; those with the lowest ratios were produced exclusively by Le^a–b+ mothers (pEscherichia coli were consuming milk with lower ratios (4.4 ± 0.8 [SE]) than the remaining infants (8.5 ± 0.8; pp = 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.