Milk Exosomes and MicroRNAs: Potential Epigenetic Regulators

  • Bodo C. Melnik
  • Foteini Kakulas
Reference work entry


The scientific perception of the biological functions of milk, mammal’s secretory product of mammary gland epithelial cells during lactation, has dramatically changed in recent years from a simple food for the newborn mammal to a most sophisticated signaling system between the mother and her infant, in addition to nourishment, protection, and development it provides. From the wide range of extracellular vesicles found in milk, this review focuses primarily on milk exosomes and exosome-delivered microRNAs that emerge as an epigenetic regulatory software of milk decreasing genome methylation of the milk recipient. Thus, milk-derived exosomes are regarded as critical signalosomes for mother-to-child transmission of microRNAs that affect epigenetic regulatory circuits of the milk recipient. Evidence accumulates that epigenetic signaling of milk promotes the development of the infant’s gastrointestinal tract, immune system, osteogenesis, myogenesis, adipogenesis, and neurogenesis. According to the functional hypothesis, milk exosomal microRNAs may reach the systemic circulation of the infant and the adult human milk consumer. Human and bovine milk exosomes and their associated microRNAs are found in the fat fraction of milk and in skim milk. microRNAs are also present in large numbers in the cellular fraction of milk, making it a microRNA-rich medium, likely the richest microRNA source of all body fluids in humans. Human milk and commercial cow’s milk provides abundant amounts of microRNA-148a, microRNA-152, microRNA-29b, and microRNA-21, which all target DNA methyltransferases (DNMTs) that potentially affect whole genome DNA methylation patterns. DNA CpG demethylation upregulates the expression of many genes including the m6A RNA demethylase fat mass- and obesity-associated protein (FTO). In this regard, milk exosomal microRNAs may function as potential epigenetic modifiers of DNA- and RNA methylation of the milk recipient, who under physiological conditions is the suckling infant, but also the human consumer of commercial cow’s milk. Whereas milk exosome-driven epigenetic signaling appears to be indispensable for adequate postnatal growth and programming of the infant, this microRNA transmitter is almost absent in artificial formula, potentially leading to faulty or immature epigenetic programming of formula-fed infants. Furthermore, persistent consumption of commercial cow’s milk that still contains bioactive microRNAs, some of which exhibit high complementarity to human milk microRNAs, has currently unknown consequences to human health and may bear a health risk for humans of developed milk-consuming civilizations.


Breastfeeding DNA methyltransferase Epigenetic regulation Epitranscriptome Growth Exosome FoxP3 FTO Infant formula Lactation microRNA Milk NRF2 NR4A3 Western diseases 

List of Abbreviations


Argonaute 2


V-AKT murine thymoma viral oncogene homolog


Cow’s milk allergy


Dopamine receptor type 2


DNA methyltransferase


Extracellular vesicle


Forkhead box P3


Fat mass- and obesity-associated gene


Glucose transporter 1


Intestinal epithelial cell


Immunoglobulin E


Insulin-like growth factor-1


Insulin-like growth factor-1 receptor




Intralumial vesicle


Nuclear factor κB inhibitor α




Lactase gene




Mammary epithelial cell


Mouse embryonic fibroblast


Milk fat globule


Milk fat globule membrane


Micro-ribonucleic acid


Mechanistic target of rapamycin complex 1


Multi-vesicular body


Necrotizing enterocolitis


Nuclear factor of κ light chain gene enhancer in B cells inhibitor α


Nuclear factor κB


Nuclear receptor subfamily 4, group A, member 3


Nuclear factor erythroid 2-related factor 2


Transformation-related protein 53


Peripheral blood mononuclear cells


PPAR-γ coactivator 1-α


Phosphatidylinositol 3-kinase


Peroxisome proliferator-activated receptor-γ


Ras guanyl nucleotide-releasing protein-1


RNA silencing complex


Ribonucleic acid


Rho-associated coiled-coil containing protein kinase 1


Runt-related transcription factor 1, translocated to, 1

S6 K1

Ribosomal protein S6 kinase


Systemic RNA interference-defective-1 transmembrane family member 1


Single nucleotide polymorphisms


Sterol regulatory element-binding protein 1


Serine/arginine-rich splicing factor-2


T cell receptor


Transforming growth factor-β


Tumor necrosis factor


Treg-specific demethylated region


Untranslated region


Vascular endothelial cell


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Dermatology, Environmental Medicine and Health TheoryUniversity of OsnabrückOsnabrückGermany
  2. 2.School of Medicine and PharmacologyThe University of Western AustraliaCrawleyAustralia

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