Oligosaccharides from human milk influence growth-related characteristics of intestinally transformed and non-transformed intestinal cells

Human milk oligosaccharides (HMO) are considered to influence the composition of the gut microflora in breastfed infants. We investigated direct effects of milk HMO fractions or individual oligosaccharides on proliferation, differentiation and apoptosis in transformed human intestinal cells (HT-29 and Caco-2) and non-transformed small intestinal epithelial crypt cells of fetal origin (human intestinal epithelial cells; HIEC). We observed growth inhibition induced by neutral and acidic HMO fractions in HT-29, Caco-2 and HIEC cells in a dose dependent manner. However, the effects varied between cell lines, i.e. HT-29 and Caco-2 cells were more sensitive than HIEC cells. In HT-29, all 16 individual neutral and acidic oligosaccharides except from the two fucosyllactoses had an inhibitory effect on cell growth. Regarding the induction of differentiation in HT-29 and HIEC cells a threshold concentration was observed at 7.5 mg/ml for neutral and acidic HMO fractions. Among individual oligosaccharides, only sialyllactoses induced differentiation in HT-29 and HIEC cells; no effect neither of fractions nor of individual oligosaccharides was found in Caco-2 cells. A strong induction of apoptosis was only detected in HT-29 and HIEC cells for neutral oligosaccharide but not for acidic fractions. HMO were shown to induce growth inhibition in intestinal cells through two different mechanisms, by suppressing cell cycle progression through induction of differentiation and/or by influencing apoptosis. As the development and maturation of digestive and absorptive processes depend on differentiation our experiments show that oligosaccharides are effective at influencing various stages in gastrointestinal development in vitro.