Loss of bioactive <scp>microRNAs</scp> in cow's milk by ultra‐high‐temperature treatment but not by pasteurization treatment

Zhang, Yangdong; Xu, Qingbiao; Hou, Jiafa; Huang, Guoxin; Zhao, Shengguo; Zheng, Nan; Wang, Jiaqi

doi:10.1002/jsfa.11607

Cited by 13 publications

(15 citation statements)

References 37 publications

(115 reference statements)

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“…Pasteurization of milk was introduced as an unproven technology without prior scientific information of its long-term effects on human health. Pasteurization combined with refrigeration allowed the large-scale introduction of milk's epigenetic signaling machinery into the human food chain, recently promoted as a nutritional and therapeutic opportunity [628] . In contrast to UHT processing of milk, milk EV-derived miRs survive pasteurization, as recently confirmed [629] .…”

Section: Discussionmentioning

confidence: 99%

The endocrine and epigenetic impact of persistent cow milk consumption on prostate carcinogenesis

Melnik¹,

John²,

Weiskirchen³

et al. 2022

jtgg

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This review analyzes the potential impact of milk-induced signal transduction on the pathogenesis of prostate cancer (PCa). Articles in PubMed until November 2021 reporting on milk intake and PCa were reviewed. Epidemiological studies identified commercial cow milk consumption as a potential risk factor of PCa. The potential impact of cow milk consumption on the pathogenesis of PCa may already begin during fetal and pubertal prostate growth, critical windows with increased vulnerability. Milk is a promotor of growth and anabolism via activating insulin-like growth factor-1 (IGF-1)/phosphatidylinositol-3 kinase (PI3K)/AKT/mechanistic target of rapamycin complex 1 (mTORC1) signaling. Estrogens, major steroid hormone components of commercial milk of persistently pregnant dairy cows, activate IGF-1 and mTORC1. Milk-derived signaling synergizes with common driver mutations of the PI3K/AKT/mTORC1 signaling pathway that intersect with androgen receptor, MFG-E8, MAPK, RUNX2, MDM4, TP53, and WNT signaling, respectively. Potential exogenously induced drivers of PCa are milk-induced elevations of growth hormone, IGF-1, MFG-E8, estrogens, phytanic acid, and aflatoxins, as well as milk exosome-derived oncogenic microRNAs including miR-148a, miR-21, and miR-29b. Commercial cow milk intake, especially the consumption of pasteurized milk, which represents the closest replica of native milk, activates PI3K-AKT-mTORC1 signaling via cow milk’s endocrine and epigenetic modes of action. Vulnerable periods for adverse nutrigenomic impacts on prostate health appear to be the fetal and pubertal growth periods, potentially priming the initiation of PCa. Cow milk-mediated overactivation of PI3K-AKT-mTORC1 signaling synergizes with the most common genetic deviations in PCa, promoting PCa initiation, progression, and early recurrence.

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Section: Discussionmentioning

confidence: 99%

The endocrine and epigenetic impact of persistent cow milk consumption on prostate carcinogenesis

Melnik¹,

John²,

Weiskirchen³

et al. 2022

jtgg

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“…About 7,000-10,000 years ago, Neolithic humans started to exploit milk from other mammalian species (89), but consumed preferentially fermented milk (89,90), which compared to raw milk contains diminished quantities of bioactive MEX miRs (91). Bovine MEX miRs are conserved by pasteurization of cow milk (72-78 ℃, for >15 s), allowing their delivery into the human food chain (92,93).…”

Section: Physiological Versus Artificial Mex Mir Signalingmentioning

confidence: 99%

“…Consumption of unfermented milk during pregnancy is associated with fetal weight gain and higher birth weight (94)(95)(96)(97)(98), an indicator of fetal growth related to placental weight (99). In contrast to fermented milk with degraded MEX (93), raw and pasteurized milk deliver bioactive MEX including miR-21 and miR-148a (11,29,92,93,100,101). Following oral gavage of bovine MEX to mice, miR-21 and miR-30d accumulated in murine placenta and embryos (35).…”

Section: Bovine Mex Mir Exposure During Pregnancymentioning

confidence: 99%

“…At that time, the presence of MEX and their miRs in pasteurized milk were unknown. Recently, the bioavailability of bovine MEX miRs in pasteurized commercial milk has been confirmed (92,93,275,276). Potential adverse health effects of milk's MEX and their intrinsic miRs are a matter of medical concern (277), because bovine MEX miRs can enter the human body and affect human gene expression (11,30,(78)(79)(80)(81)277).…”

Section: Health Risks Associated With Persistent Bovine Mex Mir Exposurementioning

confidence: 99%

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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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“…So far, only a few studies have explored whether humans can absorb a meaningful amount of certain exosomal miRNAs from cow’s milk. The findings indicated that milk-derived miRNAs in pasteurized milk are absorbed by adults in meaningful amounts, and moreover, that endogenous miRNA synthesis cannot compensate for dietary deficiency ( Baier et al, 2014 ; Zhang et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Identification of Bovine miRNAs with the Potential to Affect Human Gene Expression

et al. 2022

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Milk and other products from large mammals have emerged during human evolution as an important source of nutrition. Recently, it has been recognized that exogenous miRNAs (mRNA inhibited RNA) contained in milk and other tissues of the mammalian body can enter the human body, which in turn have the ability to potentially regulate human metabolism by affecting gene expression. We studied for exogenous miRNAs from Bos taurus that are potentially contain miRNAs from milk and that could act postprandially as regulators of human gene expression. The interaction of 17,508 human genes with 1025 bta-miRNAs, including 245 raw milk miRNAs was studied. The milk bta-miR-151-5p, bta-miR-151-3p, bta-miRNA-320 each have 11 BSs (binding sites), and bta-miRNA-345-5p, bta-miRNA-614, bta-miRNA-1296b and bta-miRNA-149 has 12, 14, 15 and 26 BSs, respectively. The bta-miR-574-5p from cow’s milk had 209 human genes in mRNAs from one to 25 repeating BSs. We found 15 bta-miRNAs that have 100% complementarity to the mRNA of 13 human target genes. Another 12 miRNAs have BSs in the mRNA of 19 human genes with 98% complementarity. The bta-miR-11975, bta-miR-11976, and bta-miR-2885 BSs are located with the overlap of nucleotide sequences in the mRNA of human genes. Nucleotide sequences of BSs of these miRNAs in 5′UTR mRNA of human genes consisted of GCC repeats with a total length of 18 nucleotides (nt) in 18 genes, 21 nt in 11 genes, 24 nt in 14 genes, and 27–48 nt in nine genes. Nucleotide sequences of BSs of bta-miR-11975, bta-miR-11976, and bta-miR-2885 in CDS mRNA of human genes consisted of GCC repeats with a total length of 18 nt in 33 genes, 21 nt in 13 genes, 24 nt in nine genes, and 27–36 nt in 11 genes. These BSs encoded polyA or polyP peptides. In only one case, the polyR (SLC24A3 gene) was encoded. The possibility of regulating the expression of human genes by exogenous bovine miRNAs is discussed.

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Loss of bioactive microRNAs in cow's milk by ultra‐high‐temperature treatment but not by pasteurization treatment

Cited by 13 publications

References 37 publications

The endocrine and epigenetic impact of persistent cow milk consumption on prostate carcinogenesis

The endocrine and epigenetic impact of persistent cow milk consumption on prostate carcinogenesis

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

Identification of Bovine miRNAs with the Potential to Affect Human Gene Expression

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