Milk formula and intestinal barrier function

Intestinal epithelial cells are located at the interface between the external environment and the inside of the body. The gut lumen contains nutrients indispensable for body growth and maintenance, the gut microbiota to aid in digestion, as well as potential toxins and irritants. The role of intestinal epithelial cells is to act as a barrier and provide information of the composition of the luminal content in the intestine to the cells dispersed in the lamina propria, including immune cells. A controlled passage of immunogenic substances through intestinal epithelial cells is possible either via a paracellular pathway or a transcellular pathway. Paracellular permeability allows passage through complex protein structures called tight junctions while the transcellular pathway allows passage through the intestinal epithelial cells by endocytosis. Despite the crucial role of intestinal barrier function in maintaining gut homeostasis, intestinal permeability is poorly described during the neonatal period, either in term or preterm neonates. Research suggests that there is a decrease in intestinal permeability with age, however literature is contradictory and no firm conclusion can be drawn due to the paucity of data. Intestinal barrier function is highly influenced by the external environment, especially lumen nutritional content. Clinical trials and animal models have shown that this is particularly true during the neonatal period where formula-feeding increases intestinal permeability. The mechanisms leading to this impaired barrier function during post-natal development have not been identified. Animal models have indicated that formula composition can be improved by reducing protein content or by adding exogenous substances naturally present in breast milk, such as polyunsaturated fatty acids, prebiotics or anti-microbial substances. Finally, long-term consequences of inaccurate development of intestinal barrier function during the neonatal period have been hypothesised to be the cause of increased sensitivity of the intestine and immune cells later in life, leading to inflammation or autoimmunity. The long-term consequences of intestinal barrier dysfunction due to formula vs. breastfeeding on gut function in adulthood have yet to be explored.