Beneficial Effects of Bovine Milk Exosomes in Metabolic Interorgan Cross-Talk

Abstract

Extracellular vesicles are membrane-enclosed secreted vesicles involved in cell-to-cell communication processes, identified in virtually all body fluids. Among extracellular vesicles, exosomes have gained increasing attention in recent years as they have unique biological origins and deliver different cargos, such as nucleic acids, proteins, and lipids, which might mediate various health processes. In particular, milk-derived exosomes are proposed as bioactive compounds of breast milk, which have been reported to resist gastric digestion and reach systemic circulation, thus being bioavailable after oral intake. In the present manuscript, we critically discuss the available evidence on the health benefits attributed to milk exosomes, and we provide an outlook for the potential future uses of these compounds. The use of milk exosomes as bioactive ingredients represents a novel avenue to explore in the context of human nutrition, and they might exert important beneficial effects at multiple levels, including but not limited to intestinal health, bone and muscle metabolism, immunity, modulation of the microbiota, growth, and development.

Milk Exosomal microRNAs: Postnatal Promoters of β Cell Proliferation but Potential Inducers of β Cell De-Differentiation in Adult Life

“…We are very concerned about the recent euphoric promotion of bovine MEX for purposes of human nutrition as well as systemic administration for medical treatments [ 353 , 584 , 585 , 586 , 587 , 588 , 589 ]. In contrast to García-Martínez et al [ 582 ], who praise the generally “beneficial effects” of bovine MEX in metabolic interorgan cross-talk, we only see a meaningful potential use of MEX for infants of mothers who cannot provide adequate breastfeeding and depend on artificial formula administration. We must ask: What happens to the pancreatic β cells when bovine MEX are systemically administered over prolonged treatment periods with the intention to improve other chronic degenerative diseases such as osteoarthritis or osteoporosis [ 590 , 591 , 592 ], chronic inflammatory intestinal diseases [ 593 , 594 , 595 , 596 ], or chronic states of tissue fibrosis [ 597 , 598 ]?…”

“…Whereas exosome miR may be valuable tools for the early monitoring of T2DM [ 1 ], the use of bovine MEX for the supposed “improvement of nutrition” and many therapeutic options [ 581 , 582 , 583 , 584 , 585 ], may be another critical experiment on humans, as the operational period of MEX miRs is physiologically restricted to the postnatal period. The artificial use of MEX beyond the period of breastfeeding may turn the highly valuable MEX for the infant [ 14 , 15 , 16 , 17 , 18 , 19 , 586 , 587 , 588 , 589 ] into diabetogenic pathogens in adult life [ 36 , 520 , 521 , 522 , 523 , 524 ].…”

Effects of Milk-Derived Extracellular Vesicles on the Colonic Transcriptome and Proteome in Murine Model

“…mEVs have been proved to transfer from milk into the plasma through the intestinal tract of the consuming organism, and to affect gene expression once absorbed by target cells, thereby interfering with the physiological and pathological processes of the consumers [ 22 , 23 , 24 ]. Reif et al reported that mEVs could be absorbed by intestine cells, exerting a therapeutic and anti-inflammatory role in DSS−induced colitis, which involves reducing the expression of IL-6 and TNF-α [ 25 ].…”

Milk Exosomal miR-27b Worsen Endoplasmic Reticulum Stress Mediated Colorectal Cancer Cell Death

“…Milk is a known source of exosome-packaged microRNA (dietary miRNAs), small noncoding RNAs containing about 19–22 nucleotides, which negatively regulate the expression of their targeted genes at the post-transcriptional level by driving the degradation of target mRNAs [ 20 , 21 ]. Milk exosomes have attracted considerable attention as a therapeutic approach in different diseased tissues [ 22 ] given their content in bioactive cargos and miRNAs, able to influence different health outcomes [ 23 ]. Exosomal miRNAs are involved in several processes affected by biogenesis and exosome contents and play an important regulatory role in a wide range of biological and pathological pathways, including cancer development [ 24 , 25 , 26 ].…”

“…Nutrition alters endogenous miRNA expression, and exogenous functional miRNAs assumed with diet are transferred and bioavailable to organisms [ 26 ]. MiRNAs from cow milk modulate crucial pathways in osteogenesis, nervous, and brain development, as well as regulation of B and T lymphocytes, macrophage activation, and modulation of the adaptative immune response [ 23 ]. Milk-derived miRNAs are also able to prevent the onset of rheumatoid arthritis and to downregulate the expression of several colitis-associated miRNAs, thus improving the macroscopic colitis histopathological scores [ 30 , 31 , 32 ].…”