The implication of the milk fat globule membrane in the functionalization of the intestinal epithelium

Abstract

Milk is a biological fluid with significant complexity in relation to its structure and composition. During the early stages of life of mammals and humans, milk is the exclusive source of nutrients for newborns. Therefore, milk must satisfy the nutritional and energy requirements of newborns necessary for their survival. The main components of milk are water, carbohydrates, proteins, and lipids, among other minor components. In recent decades, milk lipids- organised as milk fat globules (MFG) and encapsulated by its membrane, the milk fat globule membrane (MFGM)- have been widely studied not only for their role as an energy source, but also for the importance of the components and structure of the MFGM. This membrane is composed of a unique tri-layer of phospholipids, glycoproteins, transmembrane proteins, glycolipids, and cholesterol, among other minor compounds, and plays an important role in the maturation of the intestinal epithelium of infants. In contrast to breastmilk, infant formulas do not present MFGM in their composition, as the industrial processing of the infant formula removes this structure, producing differences in the maturation of intestinal epithelium between breastfed infants and formula-fed infants. Pre-clinical studies, including both in vitro and in vivo models, along with clinical trials, have demonstrated beneficial effects of MFGM in both infant and adult population. Proper functioning and development of the immune system and intestinal epithelium, establishment of the intestinal microbiota, anti-carcinogenic properties, modulation of lipid metabolism, and attenuation of neurodegenerative activity are some of the beneficial effects studied in infants and adults. However, there are several knowledge gaps still remain to be addressed regarding the mechanism of interaction between MFGM and the intestinal epithelial cells, the potential preventive or protective effect of MFGM against metabolic stress in the intestinal epithelial barrier, and- exploring an initial attempt towards a potential future application in the food industry- the influence of food matrices on the bioaccessibility of MFGM and its effect on the cell lipid metabolism. This PhD thesis aims to answer this questions regarding this emerging ingredient, MFGM, that has garnered significant attention in the food industry and presents an important relevance for consumer health.