Abstract

Milk and milk products such as infant formula (IF) play a fundamental role in serving the nutritional needs of the developing infant. Extracellular vesicles (EVs) in human (HM) and cow milk (CM) contain molecular cargo such as proteins and micro(mi)RNAs that serve as functional messengers between cells and may be of importance to infant health. Most IF is derived from a CM protein base, however differences between HM and CM EV molecular cargo have not been extensively studied. This study develops a pipeline using advanced proteomics and transcriptomics to enable cross-species comparison of milk and IF EVs. The number of nanoparticles per mL of IF is significantly reduced compared to unprocessed CM. 130 proteins and 514 miRNAs are differentially abundant between HM and CM EVs. While 90% of CM EV miRNAs are also identified in IF EVs, only 20% of CM EV proteins are identified in IF EVs. This workflow identifies key species-specific differences that can be used to optimize IF recipes and enhance infant nutrition. Improved preservation of EV functional molecular cargo in IF products is of critical importance to retaining molecular drivers of good health and should be the focus of future investigations.

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