Fucosylated human milk oligosaccharides vary between individuals and over the course of lactation

Abstract

Specific human milk oligosaccharides, especially fucosylated neutral oligosaccharides, protect infants against specific microbial pathogens. To study the concentrations of individual neutral oligosaccharides during lactation, a total of 84 milk samples were obtained from 12 women at 7 time periods during weeks 1-49 postpartum. The neutral oligosaccharides from each sample were isolated, perbenzoylated, resolved, and quantified by reversed-phase high-performance liquid chromatography. The resultant oligosaccharide peaks, identified by co-elution with authentic standards and mass spectrometry, ranged in size from tri- to octasaccharides. The total concentration of oligosaccharides declined over the course of lactation; the mean concentration at 1 year was less than half that in the first few weeks postpartum. One of the 12 donors produced milk fucosyloligosaccharides that were essentially devoid of alpha1,2 linkages (but contained alpha1,3- and alpha1,4-linked fucose) until late in lactation, consistent with the nonsecretor phenotype. In milk samples from the remaining 11 donors, fucosyloligosaccharides containing alpha1,2-linked fucose were prevalent, and their profiles were distinct from those of fucosyloligosaccharides devoid of alpha1,2-linked fucose. The ratio of alpha1,2-linked oligosaccharide concentrations to oligosaccharides devoid of alpha1,2-linked fucose changed during the first year of lactation from 5:1 to 1:1. Furthermore, the absolute and the relative concentrations of individual oligosaccharides varied substantially, both between individual donors and over the course of lactation for each individual. The patterns of milk oligosaccharides among individuals suggest the existence of many genotype subpopulations. This variation in individual oligosaccharide concentrations suggests that the protective activities of human milk could also vary among individuals and during lactation.

Human Milk Oligosaccharides: Evolution, Structures and Bioselectivity as Substrates for Intestinal Bacteria

“…In one study, a decrease in the total concentration of oligosaccharides was observed from the first weeks postpartum to about half the concentration after one year. In the same report, the absolute and relative concentrations of HMOs between individual donors and at different stages of lactation varied significantly [22]. Asakuma et al [24] analyzed the level of several neutral oligosaccharides in human milk colostrums for 3 consecutive days from 12 Japanese women.…”

“…Characterization of HMO has been accomplished using HPAEC and HPLC in combination with derivatization techniques [4,[21][22][23][24]. The identification of HMOs was based on the retention time of commercially available milk oligosaccharide standards and their quantification was relative to the amount of standards.…”

Widespread balancing selection and pathogen-driven selection at blood group antigen genes

“…As a result, a breast-fed infant is expected to be at variable risk of infectious diarrhea depending on his/her intestinal expression of H antigens and his/her mother secretion of the same molecule in milk; in this scenario, maximization of FUT2 expression in lactating epithelia might be extremely important in providing immunization to newborns. Indeed, different oligosaccharide species in human milk form part of the innate immune system with activity against different pathogens (Newburg et al 2005), and fucosyloligosaccharides containing alpha (1,2)-linked fucose are prevalent (Chaturvedi et al 2001). Women who are nonsecretors do not express measurable 2-linked fucosyloligosaccharides and the amount of milk fucosyloligosaccharides varies even among secretors (Chaturvedi et al 2001), possibly suggesting the presence of genotype differences responsible for such variation (Chaturvedi et al 2001).…”

“…Indeed, different oligosaccharide species in human milk form part of the innate immune system with activity against different pathogens (Newburg et al 2005), and fucosyloligosaccharides containing alpha (1,2)-linked fucose are prevalent (Chaturvedi et al 2001). Women who are nonsecretors do not express measurable 2-linked fucosyloligosaccharides and the amount of milk fucosyloligosaccharides varies even among secretors (Chaturvedi et al 2001), possibly suggesting the presence of genotype differences responsible for such variation (Chaturvedi et al 2001). Since diarrhea represents a very common cause of mortality in newborns throughout the world, the adaptive significance of decreasing the chance of infection in breast-fed infants is evident.…”

Probiotics, Prebiotics and Synbiotics for Infant Feeding

“…Concentration and composition of OS in human milk differ considerably among individuals and during the course of lactation [118] and contains more than 130 different oligosaccharides at a concentration of 15-23 g/L in colostrum and 8-12 g/L in transitional and mature milk [119,120]. Prebiotics are introduced in infant formulae with the objective of obtaining a bifidogenic effect identical to breast-fed infants [121] and inclusion of OS may beneficially modify the composition of the gut microbiota of formula-fed infants [122] and in immunomodulation [119] by acting as a receptor for bacteria and viral adhesion molecules [123] and stimulate the bifidus flora in the colon [124].…”