Inhibitory Effects of Milk Gangliosides on the Adhesion ofEscherichia colito Human Intestinal Carcinoma Cells

Abstract

The effects of milk gangliosides and their derivatives on the adhesion of enterotoxigenic and enteropathogenic Escherichia coli to Caco-2 cells, a human intestinal carcinoma cell line, were investigated. Human milk gangliosides inhibited the adhesion of enterotoxigenic E. coli to Caco-2 cells in the same proportion, regardless of the lactational stage, but bovine milk gangliosides were less effective. The most effective inhibitor was monosialoganglioside 1 (GM1); the adhesion rate of enterotoxigenic E. coli in the presence of GM1 was less than 20% of the positive control. The adhesion of E. coli was also depressed to 31.4% by monosialoganglioside 3 (GM3). However, the inhibitory effect of disialoganglioside 3 (GD3) was less than that of GM3. GD3 lactone, ceramide lactoside, and N-acetylneuraminic acid did not inhibit E. coli adhesion to Caco-2 cells. GM3 also inhibited the adhesion of enteropathogenic E. coli to Caco-2 cells. Thus, these results suggest that GM3 possibly behaves as a physiological component in the intestinal tract of infants to protect them against enteric infections.

The Impact of the Milk Glycobiome on the Neonate Gut Microbiota

“…The protective effects of milk gangliosides have been attributed to their glycan moieties, which function as decoys for pathogen receptors in the host cells. GM1 and GM3 inhibited ETEC adhesion to Caco-2 cells (172). GM1 from milk prevented binding of heat labile toxin (LT) from E. coli in vitro and abolished the fluid accumulation induced by cholera toxin (CT) from Vibrio cholerae in a rabbit intestinal loop model (173).…”

“…Preventive effects from bovine milk gangliosides against LT and CT require higher concentrations (174). GD3 was reported to minimally affect adhesion of ETEC and EPEC to intestinal cell lines (172). Globotriaosylceramide (Gb3), which is a neutral glycolipid in milk present in nanomolar concentrations, interacts with Shiga toxins (Stx) produced by Shigella dysenteriae and EHEC in vitro (175).…”

Defatted bovine milk fat globule membrane inhibits association of enterohaemorrhagic Escherichia coli O157:H7 with human HT-29 cells

“…E. coli adhesion mechanisms have been extensively reviewed in recent years (Croxen et al, 2013;Pereira & Giugliano, 2013) and some of the carbohydrate binding sites of EPEC and EHEC have been determined. These include intestinal glycosphingolipids (Teneberg, Ångstr€ om, & Ljungh, 2004), asialolactosamine (Vanmaele, Finlayson, & Armstrong, 1995), N-acetylgalactosamine on the surface of HeLa cells (Scaletsky, Milani, Trabulsi, & Travassos, 1988), fucosylated human milk oligosaccharides (Cravioto et al, 1991), monosialogangliosides (GM) (Idota & Kawakami, 1995) and mucintype core 2 O-glycans (Ye et al, 2015).…”

Influence of dietary gangliosides on neonatal brain development

“…Over 80% of the sialic acid in GM3 and GD3 structures remained intact under acidic conditions (pH 3-5) similar to the conditions found in an infant's stomach. 48 The pH in an infant's stomach is higher (pH 3-4) compared to the pH in an adult's stomach (pH 2). 49 Lactonization (gangliosides containing inner ester linkages) of sialic acid occurs at lower pH 48 levels and has been shown to protect the sialic acid monomer from destruction under acid conditions.…”

“…48 The pH in an infant's stomach is higher (pH 3-4) compared to the pH in an adult's stomach (pH 2). 49 Lactonization (gangliosides containing inner ester linkages) of sialic acid occurs at lower pH 48 levels and has been shown to protect the sialic acid monomer from destruction under acid conditions. 50 Dietary ganglioside can be absorbed in the small intestine and transported to different membrane sites in the body 29 ( Figure 2).…”