Dietary Gangliosides: Beneficial Effects for the Neonate and Potential Mechanism of Action

Abstract

Introduction: The content and distribution of gangliosides in human milk differ from those found in milk from other mammalian species, and also selectively change during lactation. Therefore, milk gangliosides may have a role in newborn development during early infancy. This might be to contribute to brain and neurological development, but it has also been suggested that the intestine could be a target organ for dietary gangliosides. Our group has reported that ganglioside-supplemented infant formula modifies the intestinal ecology of preterm newborns, increasing the Bifidobacteria content and lowering that of Escherichia coli. Although the exact mechanism by which dietary gangliosides modify intestinal microflora is unknown, they might act as decoys of intestinal receptors for some strains of bacteria. In addition, the potential effect on intestinal immunity has been investigated in mice at weaning. Methods: The luminal content of IgA was determined through ELISA and the number of intestinal IgA-secreting cells was analyzed by ELISPOT. In addition, to elucidate potential mechanisms of action, percentages of Th1 and Th2 lymphocyte subsets were quantified by ELISPOT and the effects of GD3 and GM3, major gangliosides in colostrum and mature human milk respectively, on the proliferative state of resting intestinal lymphocytes was also evaluated through H-Thymidine uptake. Results: Dietary gangliosides increased the number of intestinal IgA-secreting cells and the luminal content of secretory IgA. In addition supplementation of the diet with gangliosides determined an earlier development in the number of cytokine-secreting cells, and a significantly higher number of Th1 and Th2 cytokine-secreting lymphocytes in lamina propria and Peyer s patches. On the other hand, GD3 increased lymphocyte proliferation rates in all the intestinal lymphocyte populations, whereas GM3 stimulated the proliferation of intestinal lymphocytes excepting for those from Peyer’s patches. All these results suggest that dietary gangliosides influence the maturation process of the intestinal immune system that takes place during weaning according to the following potential mechanism of action. Gangliosides modulate the cytokine network promoting the secretion of some cytokines involved in the stimulation of IgA