Selected oligosaccharides from human milk induce growth inhibition, differentiation and apoptosis in intestinal cells

Abstract

Human milk oligosaccharides (HMO) have recently been discussed with regard to prebiotic effects and their immune modulating potential for breast-fed infants. However, little is known about their direct effects on the infant’s intestine. Therefore, we investigated the growth-promoting activity of HMO as well as their impact on cell differentiation and apoptosis by using human transformed and non-transformed intestinal cells (HT-29, Caco-2 and HIEC). Cells were exposed to neutral and acidic oligosaccharides in concentrations of 0–15mg/mL for 24–72 h. The highest concentrations of neutral HMO decreased intestinal cell proliferation by 41.7 ± 8.2 % in HT-29, 62.5 ± 3.5 % in Caco-2 and 77.3 ± 4.0 % in HIEC cells. Inhibition of proliferation by acidic HMOs was also distinctive: 31.6 ± 4.6 % in HT-29, 53.8 ± 8.4 % in Caco-2 and 65.7 ± 4.0 % in HIEC cells. This inhibition by neutral HMO was associated with an induction of differentiation and apoptosis, whereas acidic HMO only induced differentiation in HT-29 and HIEC cells. In addition, we investigated 18 of the most abundant HMOs in order to identify possible key compounds. All substances tested displayed significant growth reduction but few were able to induce differentiation and/or apoptosis. In conclusion, selected HMOs were shown to induce growth inhibition in different epithelial intestinal cells by two different mechanisms, i.e. by suppressing cell cycle progression through induction of differentiation and/or apoptosis.