Extracellular vesicles are lipid-bilayer nano-sized particles secreted from cells that can contain biologically active molecules, including microRNAs. MicroRNAs are regulators of posttranscriptional gene expression, and thus are able to influence a wide range of cellular processes. Their presence in extracellular vesicles mean they are capable of influencing cells at distant locations within a body, or between individuals as extracellular vesicles are present in secretions including milk. Although some studies have indicated the ability of milk-derived extracellular vesicles can be taken up by multiple cell types, it is not clear if processing milk influences extracellular vesicles or their cargo. Kleinjan and colleagues conducted a study to address this question and report their results in paper published in the June 2021 issue of The Journal of Nutrition.
Extracellular vesicles were isolated from raw, pasteurized (homogenized or not) and ultra-heat treated bovine milk. Extracellular vesicle numbers, integrity, morphology, protein cargo, as well as RNA analyses (total small RNA concentration and specific RNA expression) were determined in the milk samples.
Ultra-heat treatment destroyed extracellular vesicles. Pasteurization, with or without homogenization, did not impact the numbers of extracellular vesicles. However, pasteurization did influence the integrity, appearance, and protein cargos of the extracellular vesicles. Pasteurization also caused the loss of extracellular vesicle associated RNAs. These observations led the authors to conclude that commercial milk processing leads to the degradation in the integrity and composition of extracellular vesicles, and thus likely diminishes the transfer of bioactive components from bovines to humans.
In a commentary on this article, Cione et al, reiterate that microRNAs are vulnerable to enzymatic degradation, and that destruction of the protective lipid bilayer of extracellular vesicles would render them susceptible to these enzymes. They also point out that to effectively impact biological function, it would be necessary to have a minimum of 1000 copies of a microRNA inside a cell. They conclude that ingested microRNAs in extracellular vesicles derived from processed bovine milk may not have a biological effect, even though they can be found in human blood.
Kleinjan M, van Herwijnen MJC, Libregts SFWM, van Neerven RJJ, Feitsma AL, Wauben MHM. Regular industrial processing of bovine milk impacts the integrity and molecular composition of extracellular vesicles. The Journal of Nutrition, Volume 151, Issue 6, June 2021, Pages 1416–1425, https://doi.org/10.1093/jn/nxab031.
Cione E, Zambrini ASV, Cannataro R. MicroRNAs and extracellular vesicles in milk: RNA-based micronutrients? The Journal of Nutrition, Volume 151, Issue 6, June 2021, Pages 1378–1379, https://doi.org/10.1093/jn/nxab134.
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