Fermentation Results in Quantitative Changes in Milk-Derived Exosomes and Different Effects on Cell Growth and Survival

Abstract

The discovery of microRNAs encapsulated in milk-derived exosomes has revealed stability under extreme conditions reflecting the protection of membranes. We attempted to determine the variations in nanoparticles derived from milk after fermentation, and provide evidence to determine the effects of these exosomes on cells with potential bioactivity. Using scanning electron microscopy and dynamic light scattering, we compared the morphology and particle size distribution of exosomes from yogurt fermented with three different combinations of strains with those from raw milk. The protein content of the exosome was significantly reduced in fermented milk. The cycle threshold showed that the expression of miR-29b and miR-21 was relatively high in raw milk, indicating a loss of microRNA after fermentation. Milk-derived exosomes could promote cell growth and activate the mitogen-activated protein kinase pathway. These findings demonstrated biological functions in milk exosomes and provided new insight into the nutrient composition of dairy products.

Milk MicroRNAs in Health and Disease

“…Moreover, for milk microRNAs, bioavailability does not include their function but only their internalization and detection within the circulatory system or in different organs of the consumer (Manca et al., ; Wang et al., ; Wolf, Baier, & Zempleni, ; Zempleni et al., ). Functions of milk microRNAs are usually referred to as bioactivity (Benmoussa et al., ; Melnik et al., ; Yu, Zhao, Sun, & Li, ; Zempleni, ), and it would require a minimum of 1,000 copies of microRNAs to exert a biological function inside a cell (Williams et al., ).…”

Milk’s Role as an Epigenetic Regulator in Health and Disease

“…Ultra-sonication treatment of bovine colostrum exosomes abolished their immune-regulatory activity pointing to the critical role of exosome membrane integrity for exosome function [44]. Fermentation results in quantitative changes of milk-derived exosomes and reduction of milk miRNA levels [64]. Milk exosomes exhibit cross-species tolerance with no adverse immune and inflammatory responses [65].…”

“…The miRNA-29 family (miRNA-29a, miRNA-29b and miRNA-29c) has been detected in bovine colostrum and bovine milk [40,44,64,79]. miRNA-29b levels in PBMCs of healthy volunteers increased in a dose-dependent manner after consumption of pasteurized cow’s milk [79].…”

Human milk extracellular vesicles target nodes in interconnected signalling pathways that enhance oral epithelial barrier function and dampen immune responses

“…1E). Interestingly, others have shown a role for milk EVs of rat, porcine and bovine origin in modulating intestinal epithelial cells [17][18][19] , suggesting that supporting epithelial integrity could be a central and evolutionary conserved function of maternal milk EVs. This idea is further supported by the presence of conserved milk EV miRNA cargo with regulatory functions that are shared between mammalian species, which could aid in this process 20 .…”