Human milk oligosaccharides reduce Entamoeba histolytica adhesion and cytotoxicity in vitro

Human Milk Oligosaccharides (HMO), complex sugars highly abundant in breast milk, reduce the virulence of several microbial pathogens by inhibiting their adhesion to the host's intestinal epithelium. We hypothesize that HMO also reduce infection with the colonic parasite Entamoeba histolytica (Eh) based on two observations: 1) A major Eh virulence factor is the surface Gal/GalNAc lectin, that mediates amoebic adhesion and cytotoxicity. 2) HMO contain galactose in their polylactosamine backbone, are minimally digested and reach the colon, where Eh colonizes. We asked whether HMO reduce Eh adhesion and cytotoxicity. Our data show that physiological concentrations of pooled HMO reduce Eh adhesion in a dose-dependent manner. Co-culture experiments with HT-29 intestinal cell monolayers showed that HMO also reduce Eh mediated cytotoxicity dose-dependently. Individual HMO varied in potencies. 2′- and 3-fucosyllactose and 3′- and 6′-sialyllactose showed no effect, whereas Lacto-N-tetraose effectively reduced Eh cytotoxicity, strongly supporting a structure-dependent function, likely mediated by the Gal/GalNAc lectin. Although our results need to be confirmed in vivo, they may provide one explanation for why breast-fed infants are at lower risk for Eh infections.