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

Abstract

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.

Effects of Human Milk Oligosaccharides on the Adult Gut Microbiota and Barrier Function

“…Their concentrations in maternal milk vary according to factors such as day of lactation, mother's genetic secretor status, and birth type, but large interlaboratory variations have also been reported as reviewed previously [52]. HMOs of different structures differentially affect the function of the gut barrier of the infant helping to maintain gut health [53]. A recent clinical trial in adults showed that supplementing the diet with HMOs could be a valuable strategy to shape the human gut microbiota and specifically promote the growth of beneficial bifidobacteria [18].…”

Human Milk Oligosaccharides Differently Modulate Goblet Cells Under Homeostatic, Proinflammatory Conditions and ER Stress

“…[13] The latter, gut barrier function, is provided by tightly connected epithelial cells and mucus. hMOs are known to enhance epithelial barrier, [20,21] but the relative effects of individual oligosaccharides on stimulate mucus function have not been studied yet. HMOs are also subject to modifications during passage through the gastrointestinal tract.…”

More than sugar in the milk: human milk oligosaccharides as essential bioactive molecules in breast milk and current insight in beneficial effects

“…The intestinal mucosa of a healthy adult contains more than 80% of the body's immune cells, which makes the gastrointestinal tract the largest immunologically active organ of the human body (Lewis and Blutt 2019). Its primary function is to protect the human body from undesired intruders from the lumen of the intestine while at the same time inducing tolerance to the 100 trillion bacteria that are needed for digestive processes and for production of beneficial fermentation products such as short chain fatty acids (SCFAs) (Figueroa-Lozano and de Vos 2019;McLeod et al 2019). The mucosal immune system is integrated into a physical barrier which is composed of a mucus layer and closely connected epithelial cells that protect the host from the harsh luminal content of the gut (Okumura and Takeda 2017).…”

“…It is assumed that also closing the barrier is supported by bioactive components in mother milk (Cacho and Lawrence 2017). In addition, the bioactive molecules in mother milk support colonization of the more than 100 trillion microbiota in the small and large intestine that digest foods and produce fermentation products that are needed to support our metabolism, immunity and brain health (Figueroa-Lozano and de Vos 2019;McLeod et al 2019).…”