Milk exosomal microRNAs: friend or foe?—a narrative review

Background and Objective: Milk exosomes (MEX) and their inherent microRNAs (miRs) were recently promoted as promising effectors and drug carrier systems for the treatment of various chronic human diseases. This review intends to provide a comprehensive view on the potential beneficial and adverse health effects of MEX miRs. Methods: English literature published between 1990 and 2022 were searched using the PubMed database focusing on publications including human and bovine MEX, milk extracellular vesicles (EVs), miRs, and reported beneficial and adverse effects of MEX miRs. Key Content and Findings: MEX are regarded as signalosomes produced under control of the lactation genome to support species-specific growth of the offspring during the lactation period. Physiologically, mammals are not exposed to MEX miRs after the lactation period. MEX miRs are important for epigenetic postnatal programming and tissue maturation. Direct and translational evidence indicates that MEX miRs are involved in p53-mediated transcription, DNA methyltransferase-regulated gene silencing as well as Polycomb repressive complex-mediated gene repression and chromatin remodeling. MEX miRs are deficient in artificial formula, but may accidentally modify human gene expression by consumption of pasteurized cow milk. The continuous impact of bovine MEX miRs on the human epigenome and epitranscriptome remains a matter of concern. Conclusions: MEX miRs are supportive for the growing neonate, whereas continuous exposure of adult humans to bovine MEX miRs may promote obesity, diabetes, cancer and neurodegeneration. Bovine MEX miRs should be removed from the human food chain of adults. The efficacy and long-term safety of MEX miRs should be carefully assessed in future studies before bovine MEX could be introduced for therapeutic purposes.