Markedly difference in DNA methylation and function of the immature newborn intestine between preterm piglets fed infant formula and bovine colostrum highlight the importance of the correct early feeding regime for preterm infants.
DNA methylation is very important in tissue development. Nutrition can influence DNA methylation and may thus directly modulate intestinal cellular functions and tissue development by regulating the gene expression. The different DNA methylation patterns could possible affect intestinal health and maturation both short- and long term. This point to a potential direct link between feeding regime, intestinal development and long-term health status through epigenetic modifications.
Preterm infants have very immature gut and immune system so the first feeding regimes and gut colonization are two important environmental factors. However, little is known about the epigenetic effects of the first milk diet in preterm newborns where optimal feeding regimes are known to be critical for intestinal maturation and protection against necrotizing enterocolitis (NEC).
This study used 24 cesarean-delivered preterm piglets to investigate the DNA methylome in the immature intestine of preterm newborns and to see if DNA methylation changed in the small intestine following different feeding regimes with slow introduction of infant formula and bovine colostrum, respectively, in the first 5 days after birth.
Markedly differences in DNA methylation were found between the two feeding regimes. The nutritional origin of the methyl group is clearly important for the DNA methylation pattern, as preterm piglets fed infant formula showed an increase in the expression of genes related to innate immune response and hypoxia, together with increased bacterial epithelial adherence, when compared to piglets fed colostrum.
Formula feeding induced a markedly different intestinal DNA methylation pattern than bovine colostrum. Even a slow introduction of infant formula, which induced short-term minimal intestinal NEC lesions, resulted in molecular changes that may predispose to intestinal inflammation later.
Pigs fed infant formula also showed a dense bacterial adherence to the epithelium that may relate to lack of bioactive components with antimicrobial and immunomodulatory properties in the highly processed infant formula. They also had a decreased digestive function (e.g. lactase activity) that may relate to the increased bacterial density and fermentation and trigger a cascade of pro-inflammatory events later on. The plant-derived carbohydrates (e.g., maltodextrin and maltose) present in infant formula could be a part of the explanation for the enhanced gut colonization together with the much lower concentrations of B12 vitamin, compared to bovine colostrum.
Altogether, DNA methylation is highly diet-dependent and causes gene expressions changes that are important for intestinal functions, such as innate immune response, hypoxia, VEGF signaling and digestive capacity in preterm neonates. The changes may affect intestinal health and maturation both short- and long term.