Abstract
Extracellular vesicles (EVs) are released by all cells under pathological and physiological conditions. EVs harbor various biomolecules, including protein, lipid, non-coding RNA, messenger RNA, and DNA. In 2007, mRNA and microRNA (miRNA) carried by EVs were found to have regulatory functions in recipient cells. The biological function of EVs has since then increasingly drawn interest. Breast milk, as the most important nutritional source for infants, contains EVs in large quantities. An increasing number of studies have provided the basis for the hypothesis associated with information transmission between mothers and infants via breast milk-derived EVs. Most studies on milk-derived EVs currently focus on miRNAs. Milk-derived EVs contain diverse miRNAs, which remain stable both in vivo and in vitro; as such, they can be absorbed across different species. Further studies have confirmed that miRNAs derived from milk-derived EVs can resist the acidic environment and enzymatic hydrolysis of the digestive tract; moreover, they can be absorbed by intestinal cells in infants to perform physiological functions. miRNAs derived from milk EVs have been reported in the maturation of immune cells, regulation of immune response, formation of neuronal synapses, and development of metabolic diseases such as obesity and diabetes. This article reviews current status and advances in milk-derived EVs, including their history, biogenesis, molecular contents, and biological functions. The effects of milk-derived EVs on growth and development in both infants and adults were emphasized. Finally, the potential application and future challenges of milk-derived EVs were discussed, providing comprehensive understanding and new insight into milk-derived EVs.
Highlights
OF EVSHistory, Definition, and Biogenesis of Extracellular vesicles (EVs)Small vesicles released by the fusion of multivesicular bodies and plasma membrane in sheep reticulum were observed in 1983 by Johnstone (Pan and Johnstone, 1983), who referred to these microvesicles as “exosomes” in a 1987 study (Johnstone et al, 1987)
We mainly focus on exosomes and other EVs in milk are discussed when relevant
About 900 and 800 miRNAs have been detected in exosomes derived from human and bovine milk (Liao et al, 2017; Özdemir, 2020). (3) high stability: Compared with exogenous synthetic miRNAs, milk EV miRNAs are more resistant to harsh conditions, including repeated freeze–thaw cycles, RNA enzyme, and high temperature (Zhou et al, 2012; Liao et al, 2017; Kahn et al, 2018). (4) strong regulatory ability: miRNAs regulate 60% of human messenger RNA (mRNA) and participate in almost every biological process (Friedman et al, 2008). (5) high conservation: miRNAs are highly conserved among different species, allowing them to be used across species
Summary
The Developmental Origins of Health and Disease hypothesis, known as DoHad hypothesis, indicates that early life is the origin of health and disease in adulthood (Barker, 2007). Breast milk is rich in various nutrients, including proteins, fats, carbohydrates, minerals, and vitamins, which can provide the energy necessary for growth and development in infancy; breast milk is rich in biological ingredients, including lactoferrin, immunoglobulin, growth factors, oligosaccharides, and polyunsaturated fatty acids, among others (Victora et al, 2016). These ingredients affect the development of the gastrointestinal tract, brain, immune system, and so on in infants. This information is expected to elucidate the biological functions of milk-derived EVs
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