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 alpha 1,3- or alpha 1,4-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 alpha 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 Le(a-b-) mothers; those with the lowest ratios were produced exclusively by Le(a-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.

The Human Milk Oligosaccharide 2′-Fucosyllactose Quenches Campylobacter jejuni–Induced Inflammation in Human Epithelial Cells HEp-2 and HT-29 and in Mouse Intestinal Mucosa

“…Fucose binding is a critical determinant of C. jejuni pathogenesis and is strongly inhibited by HMOSs and by 2#-fucosyllactose (2#-FL), a major constituent of the HMOSs (10). The ability of 2#-FL to inhibit C. jejuni binding is consistent with the inverse relation between concentrations of 2-linked fucosyl oligosaccharides in milk consumed by infants and the risk of C. jejuni-caused moderate-tosevere diarrhea in a prospective study in breastfeeding motherinfant dyads (16,17). Prebiotic activity of oligosaccharides also may be protective (18,19); these indigestible glycans provide a carbon source for mutualistic bacteria that promote the colonization of the gut by a protective community of microbes.…”

“…HMOSs were prepared from pooled human milk as described previously (16). Pure 2#-FL was produced by microbial fermentation and brought to >99% purity by Glycosyn LLC.…”

Probiotics - What They Are, Their Benefits and Challenges

“…Human milk contains more galactooligosaccharides than cow's milk. Oligosaccharides can be found in levels as high as (12g/l), making them the third bulkiest constituent of human milk (Newburg et al, 2004). Taking foods containing prebiotic oligosaccharides is not enough for modulation of gut flora as they are present in only small concentrations in these foods.…”

Simultaneous quantification of sialyloligosaccharides from human milk by capillary electrophoresis

“…More than 130 different HMOS have been identified [8]. However, the amounts of HMOS expressed in human milk change during the course of lactation and vary among individuals [10,11]. To observe these differences, it is critical to have efficient, simple, quantitative methods for routine measurement of HMOS in large numbers of samples.…”