Human Milk Extracellular Vesicles: A Biological System with Clinical Implications

Abstract

The consumption of human milk by a breastfeeding infant is associated with positive health outcomes, including lower risk of diarrheal disease, respiratory disease, otitis media, and in later life, less risk of chronic disease. These benefits may be mediated by antibodies, glycoproteins, glycolipids, oligosaccharides, and leukocytes. More recently, human milk extracellular vesicles (hMEVs) have been identified. HMEVs contain functional cargos, i.e., miRNAs and proteins, that may transmit information from the mother to promote infant growth and development. Maternal health conditions can influence hMEV composition. This review summarizes hMEV biogenesis and functional contents, reviews the functional evidence of hMEVs in the maternal-infant health relationship, and discusses challenges and opportunities in hMEV research.

Keywords: breastmilk; exosomes; extracellular vesicles; human milk; maternal–child health outcomes; non-coding RNAs.

Figure 1

The number of peer-reviewed publications in the PubMed database during 2007–2022 with search terms (“human milk” OR “breastmilk”) AND (“exosomes” OR “extracellular vesicle”).

Figure 2

HMEV biogenesis and compositions. EV, extracellular vesicles; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; hMEVs, human milk extracellular vesicles; HSP, heat shock protein; ICAM-1, intercellular adhesion molecule 1; MHC, major histocompatibility complex; miRNAs, microRNAs; MUC-1, mucin-1; MVB, multivesicular bodies; PRDX1, peroxiredoxin 1; TGF-β, tumor necrosis factor-β; Tsg101, tumor susceptibility gene 101; XDH, xanthine dehydrogenase.

Figure 3

Potential clinical applications of hMEVs as predictive biomarkers of maternal–child health outcomes and as a source or inspiration for novel nutraceuticals/therapeutics. Abbreviations: TEM, transmission electron microscopy, ELISA, enzyme-linked immunosorbent assay; qRT-PCR, quantitative real-time polymerase chain reaction; NTA, nanoparticle tracking analysis; LC-MS/MS, liquid chromatography-tandem mass spectrometry; NGS, next-generation sequencing; EV, extracellular vesicles; HMEV, human milk derived extracellular vesicles.