Milk fat globules (MFGs) are a remarkable example of nature's ingenuity. Human milk (HM) carries contains 3-5% fat, 0.8-0.9% protein, 6.9-7.2% carbohydrate calculated as lactose, and 0.2% mineral constituents. Most of these nutrients are carried in these MFGs, which are composed of an energy-rich triacylglycerol (TAG) core surrounded by a triple membrane structure. The membrane contains polar lipids, specialized proteins, glycoproteins, and cholesterol. Each of these bioactive components serves important nutritional, immunological, neurological, and digestive functions. These MFGs are designed to release energy rapidly in the upper gastrointestinal tract and then persist for some time in the gut lumen so that the protective bioactive molecules are conveyed to the colon. These properties may shape the microbial colonization and innate immune properties of the developing gastrointestinal tract. Milk fat globules in milk from humans and ruminants may resemble in structure but there are considerable differences in size, profile, composition, and specific constituents. There are possibilities to not only enhance the nutritional composition in a goal-oriented fashion to correct specific deficiencies in the infant but also to use these fat globules as a nutraceutical in infants who require specific treatments. To mention a few, there might be possibilities in enhancing neurodevelopment, in defense against gastrointestinal and respiratory tract infections, improving insulin sensitivity, treating chronic inflammation, and altering plasma lipids. This review provides an overview of the composition, structure, and biological activities of the various components of the MFGs. We have assimilated research findings from our own laboratory with an extensive review of the literature utilizing key terms in multiple databases including PubMed, EMBASE, and Science Direct. To avoid bias in the identification of studies, keywords were short-listed a priori from anecdotal experience and PubMed's Medical Subject Heading (MeSH) thesaurus.
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