Structure-function relationship and impact on the gut-immune barrier function of non-digestible carbohydrates and human milk oligosaccharides applicable for infant formula

Human milk oligosaccharides (hMOs) in mothers' milk play a crucial role in guiding the colonization of microbiota and gut-immune barrier development in infants. Non-digestible carbohydrates (NDCs) such as synthetic single hMOs, galacto-oligosaccharides (GOS), inulin-type fructans and pectin oligomers have been added to infant formula to substitute some hMOs' functions. HMOs and NDCs can modulate the gut-immune barrier, which is a multiple-layered functional unit consisting of microbiota, a mucus layer, gut epithelium, and the immune system. There is increasing evidence that the structures of the complex polysaccharides may influence their efficacy in modulating the gut-immune barrier. This review focuses on the role of different structures of individual hMOs and commonly applied NDCs in infant formulas in (i) direct regulation of the gut-immune barrier in a microbiota-independent manner and in (ii) modulation of microbiota composition and microbial metabolites of these polysaccharides in a microbiota-dependent manner. Both have been shown to be essential for guiding the development of an adequate immune barrier, but the effects are very dependent on the structural features of hMO or NDC. This knowledge might lead to tailored infant formulas for specific target groups.