Experimental studies on anti-pathogenic and gut barrier enforcing effects of dietary fibers and human milk oligosaccharides

Breastfeeding has been widely recognized as the gold standard for early life nutrition. However, for a variety of reasons, about 70% of the infants can not get exclusive breastfeeding and need infant formula. Most of the infant formulas available on the market are based on cow milk, which is lacking of the unique component in mother milk, i.e. human milk oligosaccharides (hMOs). Therefore, infant formulas are usually supplemented with either synthetic hMO molecules and also non-digestible carbohydrates (NDCs). Knowledge about the biological functions of these synthetic hMO and NDC molecules is still limited. In this thesis, the effects of several hMO and NDC molecules on the intestine epithelial barrier functions and the effects on gut pathogen infections, gut commensal bacterium, as well as effects on gut microbiota were investigated. We demonstrate structure-dependent effects of hMOs and NDCs on modulating the intestine epithelial glycocalyx development, the secretory functions of goblet cells, gut pathogen adhesion, and gut microbiota fermentation. Novel mechanisms including decoy effect of hMO and NDCs on gut pathogens adhesion was investigated. This thesis also prove evidence that appropriate in vitro models need to be designed to understand the biological function of hMO and NDCs. Overall, in this thesis, we present novel mechanisms by which individual hMO and NDC molecules improve health as well as clues for designing personalized infant formula to improve the health development of infants.