Relationship Between Oligosaccharides and Glycoconjugates Content in Human Milk and the Development of the Gut Barrier

The intestinal immune barrier is considered to be the gatekeeper of the human body and rapidly develops directly after birth. Many pre- and postnatal factors influence the development of the gut-barrier, which is composed of the microbiota, the mucus, the epithelial layer and the mucosal immune system. Even minor disturbances during barrier development can have consequences for health far into adulthood. Here we critically discuss the current knowledge on which pre- and postnatal factors influence development, maturation, and maintenance of the gut immune barrier. Human milk has a unique composition and is the gold standard for adequate development of the intestinal immune barrier. Not only the influence of human milk oligosaccharides (HMOs) but also that of glycoproteins (HMGPs) is reviewed. We discuss the influence of maternal genetic factors, such as the secretor and Lewis phenotypes on breast milk fucosylation and sialylation of HMOs and HMGPs. This diversity in HMOs and HMPGs influences microbiota composition and also the development of the immune barrier. Cow milk-derived infant formula is often being used as an alternative for human breast milk. The consequences of this for proper development of the intestinal immune barrier and, in particular, the differences in the type of oligosaccharides and glycosylation patterns (sialic and fucose composition) between cow and human milk are critically discussed. Current and prospective strategies to promote proper gut-immune maturation are proposed. These might include more personalized infant formulas when breast milk is not an option.