Do the Binding Properties of Oligosaccharides in Milk Protect Human Infants from Gastrointestinal Bacteria?

The oligosaccharide fraction of human milk, the third most abundant solid constituent, consists of hundreds of structures, many of them fucosylated. Oligosaccharides may bear structural homology to cell surface glycoconjugates used as receptors by pathogens, thus protecting nursing infants. The ability of human milk to protect against heat-stable enterotoxin of Escherichia coli in suckling mice has been attributed to neutral fucosylated oligosaccharides of milk. The same phenomenon has been found in human T84 cells, allowing the mechanism of inhibition by the oligosaccharide to be studied in vitro. The oligosaccharide binds to the extracellular domain of guanylyl cyclase, thereby inhibiting the binding of stable toxin. The protective oligosaccharide is a large structure present in too low a concentration to be routinely measured directly; however, its concentration in milk may be inferred by measuring smaller, more plentiful, structurally homologous oligosaccharides. The adhesion by invasive pathogenic strains of Campylobacter to their enterocyte target is also inhibited by human milk fucosyloligosaccharides. Because Campylobacter binds H-2 type oligosaccharide structures, the concentration of protective oligosaccharide may also be inferred from the total oligosaccharide profile. The relationship between oligosaccharide profile heterogeneity in human milk and the incidence of specific gastrointestinal bacterial disease in infants consuming these milks could indicate the significance of these oligosaccharides to infant health. The efficacy of synthetic analogs of active oligosaccharides will confirm their clinical relevance and define minimum structural features essential for activity.