Perspectives on Bovine Milk-Derived Extracellular Vesicles for
                    Therapeutic Applications in Gut Health

Mun, Daye; Oh, Sangnam; Kim, Young-Hoon

doi:10.5851/kosfa.2022.e8

Cited by 9 publications

(7 citation statements)

References 86 publications

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“…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 ]?…”

Section: Discussionmentioning

confidence: 99%

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

Melnik

Schmitz

2022

IJMS

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Pancreatic β cell expansion and functional maturation during the birth-to-weaning period is driven by epigenetic programs primarily triggered by growth factors, hormones, and nutrients provided by human milk. As shown recently, exosomes derived from various origins interact with β cells. This review elucidates the potential role of milk-derived exosomes (MEX) and their microRNAs (miRs) on pancreatic β cell programming during the postnatal period of lactation as well as during continuous cow milk exposure of adult humans to bovine MEX. Mechanistic evidence suggests that MEX miRs stimulate mTORC1/c-MYC-dependent postnatal β cell proliferation and glycolysis, but attenuate β cell differentiation, mitochondrial function, and insulin synthesis and secretion. MEX miR content is negatively affected by maternal obesity, gestational diabetes, psychological stress, caesarean delivery, and is completely absent in infant formula. Weaning-related disappearance of MEX miRs may be the critical event switching β cells from proliferation to TGF-β/AMPK-mediated cell differentiation, whereas continued exposure of adult humans to bovine MEX miRs via intake of pasteurized cow milk may reverse β cell differentiation, promoting β cell de-differentiation. Whereas MEX miR signaling supports postnatal β cell proliferation (diabetes prevention), persistent bovine MEX exposure after the lactation period may de-differentiate β cells back to the postnatal phenotype (diabetes induction).

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Section: Discussionmentioning

confidence: 99%

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

Melnik

Schmitz

2022

IJMS

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“…Currently, numerous continuing studies are elucidating the functionality and role of livestock-derived EVs in livestock industry fields [44][45][46][47]. As the first to isolate rumen derived EVs, this study showed that REVs increased pathogen resistance by regulating nematode immune genes.…”

Section: Discussionmentioning

confidence: 89%

Molecular characterization and functionality of rumen-derived extracellular vesicles using a Caenorhabditis elegans animal model

Choi¹,

Mun²,

Ryu³

et al. 2023

J Anim Sci Technol

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“…The use of concentrated MEX either native or uploaded with drugs will expose the recipient to increased amounts of intrinsic MEX miRs that may exert desired gene-regulatory effects in the target tissue but may adversely affect other non-target tissues. Bovine MEX showed beneficial effects in inflammatory bowel diseases and states of fibrosis (47)(48)(49)(50)(51)469), but may promote hyperphagia, obesity, T2DM, cancer and neurodegeneration (88,90,221,277,296,351) (Table 7). Certainly, human MEX are supportive for the newborn infant and contribute to the superiority of breastfeeding compared to formula.…”

Section: Discussionmentioning

confidence: 99%

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

Melnik¹,

Weiskirchen²,

Schmitz³

2022

ExRNA

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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. It is the intention of this review to provide a comprehensive view on the potential beneficial and adverse health effects of MEX miRs.Methods: English literature published between 1990-2022 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. KeyContent 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 has to be carefully assessed in future studies before bovine MEX could be introduced for therapeutic purposes.

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Perspectives on Bovine Milk-Derived Extracellular Vesicles for Therapeutic Applications in Gut Health

Abstract: This manuscript does not require IRB/IACUC approval because there are no human and animal participants.

Cited by 9 publications

References 86 publications

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

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

Molecular characterization and functionality of rumen-derived extracellular vesicles using a Caenorhabditis elegans animal model

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

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