1932

Abstract

Exosomes are natural nanoparticles that play an important role in cell-to-cell communication. Communication is achieved through the transfer of cargos, such as microRNAs, from donor to recipient cells and binding of exosomes to cell surface receptors. Exosomes and their cargos are also obtained from dietary sources, such as milk. Exosome and cell glycoproteins are crucial for intestinal uptake. A large fraction of milk exosomes accumulates in the brain, whereas the tissue distribution of microRNA cargos varies among distinct species of microRNA. The fraction of milk exosomes that escapes absorption elicits changes in microbial communities in the gut. Dietary depletion of exosomes and their cargos causes a loss of circulating microRNAs and elicits phenotypes such as loss of cognitive performance, increase in purine metabolites, loss of fecundity, and changes in the immune response. Milk exosomes meet the definition of bioactive food compounds.

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2019-02-15
2024-12-09
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Literature Cited

  1. 1.  Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ, Lotvall JO 2007. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat. Cell Biol. 9:654–59
    [Google Scholar]
  2. 2.  Hansen LL, Nielsen ME 2017. Plant exosomes: Using an unconventional exit to prevent pathogen entry?. J. Exp. Bot. 69:59–68
    [Google Scholar]
  3. 3.  Wolf JM, Casadevall A 2014. Challenges posed by extracellular vesicles from eukaryotic microbes. Curr. Opin. Microbiol. 22C:73–78
    [Google Scholar]
  4. 4.  György B, Szabó TG, Pásztói M, Pál Z, Misják P et al. 2011. Membrane vesicles, current state-of-the-art: emerging role of extracellular vesicles. Cell. Mol. Life Sci. 68:2667–88
    [Google Scholar]
  5. 5.  Zempleni J, Aguilar-Lozano A, Sadri M, Sukreet S, Manca S et al. 2017. Biological activities of extracellular vesicles and their cargos from bovine and human milk in humans and implications for infants. J. Nutr. 147:3–10
    [Google Scholar]
  6. 6.  Yanez-Mo M, Siljander PR, Andreu Z, Zavec AB, Borras FE et al. 2015. Biological properties of extracellular vesicles and their physiological functions. J. Extracell. Vesicles 4:27066
    [Google Scholar]
  7. 7.  Abels ER, Breakefield XO 2016. Introduction to extracellular vesicles: biogenesis, RNA cargo selection, content, release, and uptake. Cell. Mol. Neurobiol. 36:301–12
    [Google Scholar]
  8. 8.  Huang X, Yuan T, Tschannen M, Sun Z, Jacob H et al. 2013. Characterization of human plasma-derived exosomal RNAs by deep sequencing. BMC Genom 14:319
    [Google Scholar]
  9. 9.  Raposo G, Stoorvogel W 2013. Extracellular vesicles: exosomes, microvesicles, and friends. J. Cell Biol. 200:373–83
    [Google Scholar]
  10. 10.  Hurley JH 2008. ESCRT complexes and the biogenesis of multivesicular bodies. Curr. Opin. Cell Biol. 20:4–11
    [Google Scholar]
  11. 11.  Trajkovic K, Hsu C, Chiantia S, Rajendran L, Wenzel D et al. 2008. Ceramide triggers budding of exosome vesicles into multivesicular endosomes. Science 319:1244–47
    [Google Scholar]
  12. 12.  Lässer C, Alikhani VS, Ekström K, Eldh M, Paredes PT et al. 2011. Human saliva, plasma and breast milk exosomes contain RNA: uptake by macrophages. J. Transl. Med. 9:9
    [Google Scholar]
  13. 13.  Gu Y, Li M, Wang T, Liang Y, Zhong Z et al. 2012. Lactation-related microRNA expression profiles of porcine breast milk exosomes. PLOS ONE 7:e43691
    [Google Scholar]
  14. 14.  Baier SR, Nguyen C, Xie F, Wood JR, Zempleni J 2014. MicroRNAs are absorbed in biologically meaningful amounts from nutritionally relevant doses of cow's milk and affect gene expression in peripheral blood mononuclear cells, HEK-293 kidney cell cultures, and mouse livers. J. Nutr. 144:1495–500
    [Google Scholar]
  15. 15.  Yassin AM, Hamid MIA, Farid OA, Amer H, Warda M 2016. Dromedary milk exosomes as mammary transcriptome nano-vehicle: their isolation, vesicular and phospholipidomic characterizations. J. Adv. Res. 7:749–56
    [Google Scholar]
  16. 16.  Ma J, Wang C, Long K, Zhang H, Zhang J et al. 2017. Exosomal microRNAs in giant panda (Ailuropoda melanoleuca) breast milk: potential maternal regulators for the development of newborn cubs. Sci. Rep. 7:3507
    [Google Scholar]
  17. 17.  Golan-Gerstl R, Elbaum Shiff Y, Moshayoff V, Schecter D, Leshkowitz D, Reif S 2017. Characterization and biological function of milk-derived miRNAs. Mol. Nutr. Food Res. 61:1700009
    [Google Scholar]
  18. 18.  Chauhan S, Danielson S, Clements V, Edwards N, Ostrand-Rosenberg S, Fenselau C 2017. Surface glycoproteins of exosomes shed by myeloid-derived suppressor cells contribute to function. J. Proteome Res. 16:238–46
    [Google Scholar]
  19. 19.  Liu X, Pu Y, Cron K, Deng L, Kline J et al. 2015. CD47 blockade triggers T cell-mediated destruction of immunogenic tumors. Nat. Med. 21:1209–15
    [Google Scholar]
  20. 20.  Escrevente C, Keller S, Altevogt P, Costa J 2011. Interaction and uptake of exosomes by ovarian cancer cells. BMC Cancer 11:108
    [Google Scholar]
  21. 21.  Mathivanan S, Fahner CJ, Reid GE, Simpson RJ 2012. ExoCarta 2012: database of exosomal proteins, RNA and lipids. Nucleic Acids Res 40:D1241–D44
    [Google Scholar]
  22. 22.  Kalra H, Simpson RJ, Ji H, Aikawa E, Altevogt P et al. 2012. Vesiclepedia: a compendium for extracellular vesicles with continuous community annotation. PLOS Biol 12:e1001450
    [Google Scholar]
  23. 23.  Li M, Zeringer E, Barta T, Schageman J, Cheng A, Vlassov AV 2014. Analysis of the RNA content of the exosomes derived from blood serum and urine and its potential as biomarkers. Philos. Trans. R. Soc. Lond. B Biol. Sci. 369:20130502
    [Google Scholar]
  24. 24.  Freedman JE, Gerstein M, Mick E, Rozowsky J, Levy D et al. 2016. Diverse human extracellular RNAs are widely detected in human plasma. Nat. Commun. 7:11106
    [Google Scholar]
  25. 25.  Spornraft M, Kirchner B, Haase B, Benes V, Pfaffl MW, Riedmaier I 2014. Optimization of extraction of circulating RNAs from plasma–enabling small RNA sequencing. PLOS ONE 9:e107259
    [Google Scholar]
  26. 26.  Heintz-Buschart A, Yusuf D, Kaysen A, Etheridge A, Fritz JV et al. 2018. Small RNA profiling of low biomass samples: identification and removal of contaminants. BMC Biol 16:52
    [Google Scholar]
  27. 27.  Habier J, May P, Heintz-Buschart A, Ghosal A, Wienecke-Baldacchino AK et al. 2018. Extraction and analysis of RNA isolated from pure bacteria-derived outer membrane vesicles. Methods Mol. Biol. 1737:213–30
    [Google Scholar]
  28. 28.  Batagov AO, Kurochkin IV 2013. Exosomes secreted by human cells transport largely mRNA fragments that are enriched in the 3′-untranslated regions. Biol. Direct 8:12
    [Google Scholar]
  29. 29.  Vallabhajosyula P, Korutla L, Habertheuer A, Yu M, Rostami S et al. 2017. Tissue-specific exosome biomarkers for noninvasively monitoring immunologic rejection of transplanted tissue. J. Clin. Investig. 127:1375–91
    [Google Scholar]
  30. 30.  Fernandez-Valverde SL, Taft RJ, Mattick JS 2010. Dynamic isomiR regulation in Drosophila development. RNA 16:1881–88
    [Google Scholar]
  31. 31.  Tarallo S, Pardini B, Mancuso G, Rosa F, Di Gaetano C et al. 2014. MicroRNA expression in relation to different dietary habits: a comparison in stool and plasma samples. Mutagenesis 29:385–91
    [Google Scholar]
  32. 32.  Aoi W, Ichikawa H, Mune K, Tanimura Y, Mizushima K et al. 2013. Muscle-enriched microRNA miR-486 decreases in circulation in response to exercise in young men. Front. Physiol. 4:80
    [Google Scholar]
  33. 33.  Kozomara A, Griffiths-Jones S 2014. miRBase: annotating high confidence microRNAs using deep sequencing data. Nucleic Acids Res 42:D68–D73
    [Google Scholar]
  34. 34.  Stevanato L, Thanabalasundaram L, Vysokov N, Sinden JD 2016. Investigation of content, stoichiometry and transfer of miRNA from human neural stem cell line derived exosomes. PLOS ONE 11:e0146353
    [Google Scholar]
  35. 35.  Squadrito ML, Baer C, Burdet F, Maderna C, Gilfillan GD et al. 2014. Endogenous RNAs modulate microRNA sorting to exosomes and transfer to acceptor cells. Cell Rep 8:1432–46
    [Google Scholar]
  36. 36.  Li Y, Zheng Q, Bao C, Li S, Guo W et al. 2015. Circular RNA is enriched and stable in exosomes: a promising biomarker for cancer diagnosis. Cell Res 25:981–84
    [Google Scholar]
  37. 37.  Shurtleff MJ, Temoche-Diaz MM, Karfilis KV, Ri S, Schekman R 2016. Y-box protein 1 is required to sort microRNAs into exosomes in cells and in a cell-free reaction. eLife 5:e19276
    [Google Scholar]
  38. 38.  Cha DJ, Franklin JL, Dou Y, Liu Q, Higginbotham JN et al. 2015. KRAS-dependent sorting of miRNA to exosomes. eLife 4:e07197
    [Google Scholar]
  39. 39.  Janas T, Janas MM, Sapon K, Janas T 2015. Mechanisms of RNA loading into exosomes. FEBS Lett 589:1391–98
    [Google Scholar]
  40. 40.  Ge Q, Zhou Y, Lu J, Bai Y, Xie X, Lu Z 2014. miRNA in plasma exosome is stable under different storage conditions. Molecules 19:1568–75
    [Google Scholar]
  41. 41.  Lotvall J, Hill AF, Hochberg F, Buzas EI, Di Vizio D et al. 2014. Minimal experimental requirements for definition of extracellular vesicles and their functions: a position statement from the International Society for Extracellular Vesicles. J. Extracell. Vesicles 3:26913
    [Google Scholar]
  42. 42.  Oksvold MP, Kullmann A, Forfang L, Kierulf B, Li M et al. 2014. Expression of B-cell surface antigens in subpopulations of exosomes released from B-cell lymphoma cells. Clin. Ther. 36:847–62.e1
    [Google Scholar]
  43. 43.  Horejsi V, Vlcek C 1991. Novel structurally distinct family of leucocyte surface glycoproteins including CD9, CD37, CD53 and CD63. FEBS Lett 288:1–4
    [Google Scholar]
  44. 44.  Moreno-Gonzalo O, Villarroya-Beltri C, Sánchez-Madrid F 2014. Post-translational modifications of exosomal proteins. Front. Immunol. 5:383
    [Google Scholar]
  45. 45.  Sterzenbach U, Putz U, Low LH, Silke J, Tan SS, Howitt J 2017. Engineered exosomes as vehicles for biologically active proteins. Mol. Ther. 25:1269–78
    [Google Scholar]
  46. 46.  Subra C, Laulagnier K, Perret B, Record M 2007. Exosome lipidomics unravels lipid sorting at the level of multivesicular bodies. Biochimie 89:205–12
    [Google Scholar]
  47. 47.  Laulagnier K, Grand D, Dujardin A, Hamdi S, Vincent-Schneider H et al. 2004. PLD2 is enriched on exosomes and its activity is correlated to the release of exosomes. FEBS Lett 572:11–14
    [Google Scholar]
  48. 48.  Laulagnier K, Motta C, Hamdi S, Roy S, Fauvelle F et al. 2004. Mast cell– and dendritic cell–derived exosomes display a specific lipid composition and an unusual membrane organization. Biochem. J. 380:161–71
    [Google Scholar]
  49. 49.  Takahashi A, Okada R, Nagao K, Kawamata Y, Hanyu A et al. 2017. Exosomes maintain cellular homeostasis by excreting harmful DNA from cells. Nat. Commun. 8:15287
    [Google Scholar]
  50. 50.  Kahlert C, Melo SA, Protopopov A, Tang J, Seth S et al. 2014. Identification of double-stranded genomic DNA spanning all chromosomes with mutated KRAS and p53 DNA in the serum exosomes of patients with pancreatic cancer. J. Biol. Chem. 289:3869–75
    [Google Scholar]
  51. 51.  San Lucas FA, Allenson K, Bernard V, Castillo J, Kim DU et al. 2016. Minimally invasive genomic and transcriptomic profiling of visceral cancers by next-generation sequencing of circulating exosomes. Ann. Oncol. 27:635–41
    [Google Scholar]
  52. 52.  Thakur BK, Zhang H, Becker A, Matei I, Huang Y et al. 2014. Double-stranded DNA in exosomes: a novel biomarker in cancer detection. Cell Res 24:766–69
    [Google Scholar]
  53. 53.  Sansone P, Savini C, Kurelac I, Chang Q, Amato LB et al. 2017. Packaging and transfer of mitochondrial DNA via exosomes regulate escape from dormancy in hormonal therapy–resistant breast cancer. PNAS 114:E9066–E75
    [Google Scholar]
  54. 54.  Escrevente C, Grammel N, Kandzia S, Zeiser J, Tranfield EM et al. 2013. Sialoglycoproteins and N-glycans from secreted exosomes of ovarian carcinoma cells. PLOS ONE 8:e78631
    [Google Scholar]
  55. 55.  Feng M, Chen JY, Weissman-Tsukamoto R, Volkmer JP, Ho PY et al. 2015. Macrophages eat cancer cells using their own calreticulin as a guide: roles of TLR and Btk. PNAS 112:2145–50
    [Google Scholar]
  56. 56.  Purushothaman A, Bandari SK, Liu J, Mobley JA, Brown EE, Sanderson RD 2016. Fibronectin on the surface of myeloma cell-derived exosomes mediates exosome-cell interactions. J. Biol. Chem. 291:1652–63
    [Google Scholar]
  57. 57.  Muller L, Mitsuhashi M, Simms P, Gooding WE, Whiteside TL 2016. Tumor-derived exosomes regulate expression of immune function-related genes in human T cell subsets. Sci. Rep. 6:20254
    [Google Scholar]
  58. 58.  Schirle NT, MacRae IJ 2012. The crystal structure of human Argonaute2. Science 336:1037–40
    [Google Scholar]
  59. 59.  Schirle NT, Sheu-Gruttadauria J, MacRae IJ 2014. Structural basis for microRNA targeting. Science 346:608–13
    [Google Scholar]
  60. 60.  Friedman RC, Farh KK, Burge CB, Bartel DP 2009. Most mammalian mRNAs are conserved targets of microRNAs. Genome Res 19:92–105
    [Google Scholar]
  61. 61.  Zhou H, Rigoutsos I 2014. MiR-103a-3p targets the 5′ UTR of GPRC5A in pancreatic cells. RNA 20:1431–39
    [Google Scholar]
  62. 62.  Xu W, San Lucas A, Wang Z, Liu Y 2014. Identifying microRNA targets in different gene regions. BMC Bioinform 15:Suppl. 7S4
    [Google Scholar]
  63. 63.  Martinez J, Tuschl T 2004. RISC is a 5′ phosphomonoester-producing RNA endonuclease. Genes Dev 18:975–80
    [Google Scholar]
  64. 64.  Fabbri M, Paone A, Calore F, Galli R, Gaudio E et al. 2012. MicroRNAs bind to Toll-like receptors to induce prometastatic inflammatory response. PNAS 109:E2110–E16
    [Google Scholar]
  65. 65.  Doan T, Melvold R, Viselli S, Waltenbaugh C 2008. Immunology Philadelphia, PA: Wolters Kluwer Health/Lippincott Williams & Wilkins
    [Google Scholar]
  66. 66.  Harrington JM, Shannon HS 1974. Letter: Epidemic of aortic aneurysm?. Lancet 2:1575
    [Google Scholar]
  67. 67.  Sabroe I, Dower SK, Whyte MK 2005. The role of Toll-like receptors in the regulation of neutrophil migration, activation, and apoptosis. Clin. Infect. Dis. 41:Suppl. 7S421–S26
    [Google Scholar]
  68. 68.  Sallusto F, Lanzavecchia A 2002. The instructive role of dendritic cells on T-cell responses. Arthritis Res. Ther. 4:Suppl. 3S127–S32
    [Google Scholar]
  69. 69.  Yarovinsky F, Zhang D, Andersen JF, Bannenberg GL, Serhan CN et al. 2005. TLR11 activation of dendritic cells by a protozoan profilin-like protein. Science 308:1626–29
    [Google Scholar]
  70. 70.  Pifer R, Benson A, Sturge CR, Yarovinsky F 2011. UNC93B1 is essential for TLR11 activation and IL-12-dependent host resistance to Toxoplasma gondii. J. Biol. Chem. 286:3307–14
    [Google Scholar]
  71. 71.  Koblansky AA, Jankovic D, Oh H, Hieny S, Sungnak W et al. 2013. Recognition of profilin by Toll-like receptor 12 is critical for host resistance to Toxoplasma gondii. . Immunity 38:119–30
    [Google Scholar]
  72. 72.  Mishra BB, Gundra UM, Teale JM 2008. Expression and distribution of Toll-like receptors 11–13 in the brain during murine neurocysticercosis. J. Neuroinflamm. 5:53
    [Google Scholar]
  73. 73.  Shi Z, Cai Z, Sanchez A, Zhang T, Wen S et al. 2011. A novel Toll-like receptor that recognizes vesicular stomatitis virus. J. Biol. Chem. 286:4517–24
    [Google Scholar]
  74. 74.  Oldenburg M, Kruger A, Ferstl R, Kaufmann A, Nees G et al. 2012. TLR13 recognizes bacterial 23S rRNA devoid of erythromycin resistance-forming modification. Science 337:1111–15
    [Google Scholar]
  75. 75.  Tatematsu M, Nishikawa F, Seya T, Matsumoto M 2013. Toll-like receptor 3 recognizes incomplete stem structures in single-stranded viral RNA. Nat. Commun. 4:1833
    [Google Scholar]
  76. 76.  Forsbach A, Samulowitz U, Volp K, Hofmann HP, Noll B et al. 2011. Dual or triple activation of TLR7, TLR8, and/or TLR9 by single-stranded oligoribonucleotides. Nucleic Acid Ther 21:423–36
    [Google Scholar]
  77. 77.  Eigenbrod T, Dalpke AH 2015. Bacterial RNA: an underestimated stimulus for innate immune responses. J. Immunol. 195:411–18
    [Google Scholar]
  78. 78.  Magini D, Giovani C, Mangiavacchi S, Maccari S, Cecchi R et al. 2016. Self-amplifying mRNA vaccines expressing multiple conserved influenza antigens confer protection against homologous and heterosubtypic viral challenge. PLOS ONE 11:e0161193
    [Google Scholar]
  79. 79.  Rivera J, Cordero RJ, Nakouzi AS, Frases S, Nicola A, Casadevall A 2010. Bacillus anthracis produces membrane-derived vesicles containing biologically active toxins. PNAS 107:19002–7
    [Google Scholar]
  80. 80.  Lee J, Lee EY, Kim SH, Kim DK, Park KS et al. 2013. Staphylococcus aureus extracellular vesicles carry biologically active β-lactamase. Antimicrob. Agents Chemother. 57:2589–95
    [Google Scholar]
  81. 81.  Silverman JM, Clos J, de'Oliveira CC, Shirvani O, Fang Y et al. 2010. An exosome-based secretion pathway is responsible for protein export from Leishmania and communication with macrophages. J. Cell Sci. 123:842–52
    [Google Scholar]
  82. 82.  Meckes DG Jr. 2015. Exosomal communication goes viral. J. Virol. 89:5200–3
    [Google Scholar]
  83. 83.  Zhang L, Hou D, Chen X, Li D, Zhu L et al. 2012. Exogenous plant MIR168a specifically targets mammalian LDLRAP1: evidence of cross-kingdom regulation by microRNA. Cell Res 22:107–26
    [Google Scholar]
  84. 84.  Shu J, Chiang K, Zempleni J, Cui J 2015. Computational characterization of exogenous microRNAs that can be transferred into human circulation. PLOS ONE 10:e0140587
    [Google Scholar]
  85. 85.  Wang L, Sadri M, Giraud D, Zempleni J 2018. RNase H2-dependent polymerase chain reaction and elimination of confounders in sample collection, storage, and analysis strengthen evidence that microRNAs in bovine milk are bioavailable in humans. J. Nutr. 148:153–59
    [Google Scholar]
  86. 86.  Wolf T, Baier SR, Zempleni J 2015. The intestinal transport of bovine milk exosomes is mediated by endocytosis in human colon carcinoma caco-2 cells and rat small intestinal IEC-6 cells. J. Nutr. 145:2201–6
    [Google Scholar]
  87. 87.  Izumi H, Tsuda M, Sato Y, Kosaka N, Ochiya T et al. 2015. Bovine milk exosomes contain microRNA and mRNA and are taken up by human macrophages. J. Dairy Sci. 98:2920–33
    [Google Scholar]
  88. 88.  Kusuma Jati R, Manca S, Friemel T, Sukreet S, Nguyen C, Zempleni J 2016. Human vascular endothelial cells transport foreign exosomes from cow's milk by endocytosis. Am. J. Physiol. Cell Physiol. 310:C800–C7
    [Google Scholar]
  89. 89.  Sukreet S, Zhang H, Adamec J, Cui J, Zempleni J 2017. Identification of glycoproteins on the surface of bovine milk exosomes and intestinal cells that facilitate exosome uptake in human colon carcinoma Caco-2 cells. FASEB J 31:646.25
    [Google Scholar]
  90. 90.  Krogh A, Larsson B, von Heijne G, Sonnhammer ELL 2001. Predicting transmembrane protein topology with a hidden Markov model: application to complete genomes. J. Mol. Biol. 305:3567–80
    [Google Scholar]
  91. 91.  Julenius K 2007. NetCGlyc 1.0: prediction of mammalian C-mannosylation sites. Glycobiology 17:868–76
    [Google Scholar]
  92. 92.  Gupta R, Jiung E, Brunak S 2004. NetNGlyc 1.0 Server Lyngby, Den.: Tech. Univ. Den. accessed May 1, 2018. http://www.cbs.dtu.dk/services/NetNGlyc/
    [Google Scholar]
  93. 93.  Steentoft C, Vakhrushev SY, Joshi HJ, Kong Y, Vester-Christensen MB et al. 2013. Precision mapping of the human O-GalNAc glycoproteome through SimpleCell technology. EMBO J 32:1478–88
    [Google Scholar]
  94. 94.  Takov K, Yellon DM, Davidson SM 2017. Confounding factors in vesicle uptake studies using fluorescent lipophilic membrane dyes. J. Extracell. Vesicles 6:1388731
    [Google Scholar]
  95. 95.  Manca S, Upadhyaya B, Mutai E, Desaulniers AT, Cederberg RA et al. 2018. Milk exosomes are bioavailable and distinct microRNA cargos have unique tissue distribution patterns. Sci. Rep. 8:11321
    [Google Scholar]
  96. 96.  Munagala R, Aqil F, Jeyabalan J, Gupta RC 2016. Bovine milk-derived exosomes for drug delivery. Cancer Lett 371:48–61
    [Google Scholar]
  97. 97.  Imai T, Takahashi Y, Nishikawa M, Kato K, Morishita M et al. 2015. Macrophage-dependent clearance of systemically administered B16BL6-derived exosomes from the blood circulation in mice. J. Extracell. Vesicles 4:26238
    [Google Scholar]
  98. 98.  Chen X, Gao C, Li H, Huang L, Sun Q et al. 2010. Identification and characterization of microRNAs in raw milk during different periods of lactation, commercial fluid, and powdered milk products. Cell Res 20:1128–37
    [Google Scholar]
  99. 99.  Izumi H, Kosaka N, Shimizu T, Sekine K, Ochiya T, Takase M 2012. Bovine milk contains microRNA and messenger RNA that are stable under degradative conditions. J. Dairy Sci. 95:4831–41
    [Google Scholar]
  100. 100.  Sun J, Aswath K, Schroeder SG, Lippolis JD, Reinhardt TA, Sonstegard TS 2015. MicroRNA expression profiles of bovine milk exosomes in response to Staphylococcus aureus infection. BMC Genom 16:806
    [Google Scholar]
  101. 101.  Cai M, He H, Jia X, Chen S, Wang J et al. 2018. Genome-wide microRNA profiling of bovine milk-derived exosomes infected with Staphylococcus aureus. . Cell Stress Chaperones 23:663–72
    [Google Scholar]
  102. 102.  Zhou Q, Li M, Wang X, Li Q, Wang T et al. 2012. Immune-related microRNAs are abundant in breast milk exosomes. Int. J. Biol. Sci. 8:118–23
    [Google Scholar]
  103. 103.  Chen T, Xi QY, Ye RS, Cheng X, Qi QE et al. 2014. Exploration of microRNAs in porcine milk exosomes. BMC Genom 15:100
    [Google Scholar]
  104. 104.  Benmoussa A, Lee CH, Laffont B, Savard P, Laugier J et al. 2016. Commercial dairy cow milk microRNAs resist digestion under simulated gastrointestinal tract conditions. J. Nutr. 146:2206–15
    [Google Scholar]
  105. 105.  Howard KM, Jati Kusuma R, Baier SR, Friemel T, Markham L et al. 2015. Loss of miRNAs during processing and storage of cow's (Bos taurus) milk. J. Agric. Food Chem. 63:588–92
    [Google Scholar]
  106. 106.  Ebert MS, Neilson JR, Sharp PA 2007. MicroRNA sponges: competitive inhibitors of small RNAs in mammalian cells. Nat. Methods 4:721–26
    [Google Scholar]
  107. 107.  Chen T, Xie MY, Sun JJ, Ye RS, Cheng X et al. 2016. Porcine milk-derived exosomes promote proliferation of intestinal epithelial cells. Sci. Rep. 6:33862
    [Google Scholar]
  108. 108.  Cavalieri D, Rizzetto L, Tocci N, Rivero D, Asquini E et al. 2016. Plant microRNAs as novel immunomodulatory agents. Sci. Rep. 6:25761
    [Google Scholar]
  109. 109.  Wang K, Li H, Yuan Y, Etheridge A, Zhou Y et al. 2012. The complex exogenous RNA spectra in human plasma: An interface with human gut biota?. PLOS ONE 7:e51009
    [Google Scholar]
  110. 110.  Ju S, Mu J, Dokland T, Zhuang X, Wang Q et al. 2013. Grape exosome-like nanoparticles induce intestinal stem cells and protect mice from DSS-induced colitis. Mol. Ther. 21:1345–57
    [Google Scholar]
  111. 111.  Mu J, Zhuang X, Wang Q, Jiang H, Deng ZB et al. 2014. Interspecies communication between plant and mouse gut host cells through edible plant derived exosome-like nanoparticles. Mol. Nutr. Food Res. 58:1561–73
    [Google Scholar]
  112. 112.  Lukasik A, Zielenkiewicz P 2014. In silico identification of plant miRNAs in mammalian breast milk exosomes—a small step forward?. PLOS ONE 9:e99963
    [Google Scholar]
  113. 113.  Beatty M, Guduric-Fuchs J, Brown E, Bridgett S, Chakravarthy U et al. 2014. Small RNAs from plants, bacteria and fungi within the order Hypocreales are ubiquitous in human plasma. BMC Genom 15:933
    [Google Scholar]
  114. 114.  Liang G, Zhu Y, Sun B, Shao Y, Jing A et al. 2014. Assessing the survival of exogenous plant microRNA in mice. Food Sci. Nutr. 2:380–88
    [Google Scholar]
  115. 115.  Zhou Z, Li X, Liu J, Dong L, Chen Q et al. 2015. Honeysuckle-encoded atypical microRNA2911 directly targets influenza A viruses. Cell Res 25:39–49
    [Google Scholar]
  116. 116.  Yang J, Farmer LM, Agyekum AA, Hirschi KD 2015. Detection of dietary plant-based small RNAs in animals. Cell Res 25:517–20
    [Google Scholar]
  117. 117.  Mlotshwa S, Pruss GJ, MacArthur JL, Endres MW, Davis C et al. 2015. A novel chemopreventive strategy based on therapeutic microRNAs produced in plants. Cell Res 25:521–24
    [Google Scholar]
  118. 118.  Chin AR, Fong MY, Somlo G, Wu J, Swiderski P et al. 2016. Cross-kingdom inhibition of breast cancer growth by plant miR159. Cell Res 26:217–28
    [Google Scholar]
  119. 119.  Chen X, Dai GH, Ren ZM, Tong YL, Yang F, Zhu YQ 2016. Identification of dietetically absorbed rapeseed (Brassica campestris L.) bee pollen microRNAs in serum of mice. Biomed. Res. Int. 2016:5413849
    [Google Scholar]
  120. 120.  Luo Y, Wang P, Wang X, Wang Y, Mu Z et al. 2017. Detection of dietetically absorbed maize-derived microRNAs in pigs. Sci. Rep. 7:645
    [Google Scholar]
  121. 121.  Cui J, Zhou B, Ross SA, Zempleni J 2017. Nutrition, microRNAs, and human health. Adv. Nutr. 8:105–12
    [Google Scholar]
  122. 122.  Laubier J, Castille J, Le Guillou S, Le Provost F 2015. No effect of an elevated miR-30b level in mouse milk on its level in pup tissues. RNA Biol 12:26–29
    [Google Scholar]
  123. 123.  Auerbach A, Vyas G, Li A, Halushka M, Witwer K 2016. Uptake of dietary milk miRNAs by adult humans: a validation study. F1000Res 5:721
    [Google Scholar]
  124. 124.  Title AC, Denzler R, Stoffel M 2015. Uptake and function studies of maternal milk-derived microRNAs. J. Biol. Chem. 290:23680–91
    [Google Scholar]
  125. 125.  Kang W, Bang-Berthelsen CH, Holm A, Houben AJ, Muller AH et al. 2017. Survey of 800+ data sets from human tissue and body fluid reveals xenomiRs are likely artifacts. RNA 23:433–45
    [Google Scholar]
  126. 126.  Pond SM, Tozer TN 1984. First-pass elimination: basic concepts and clinical consequences. Clin. Pharmacokinet. 9:1–25
    [Google Scholar]
  127. 127.  Zempleni J, Baier SR, Hirschi K 2015. Diet-responsive microRNAs are likely exogenous. J. Biol. Chem. 290:25197
    [Google Scholar]
  128. 128.  Snow JW, Hale AE, Isaacs SK, Baggish AL, Chan SY 2013. Ineffective delivery of diet-derived microRNAs to recipient animal organisms. RNA Biol 10:1107–16
    [Google Scholar]
  129. 129.  Ameres SL, Horwich MD, Hung JH, Xu J, Ghildiyal M et al. 2010. Target RNA-directed trimming and tailing of small silencing RNAs. Science 328:1534–39
    [Google Scholar]
  130. 130.  Ruegger S, Grosshans H 2012. MicroRNA turnover: when, how, and why. Trends Biochem. Sci. 37:436–46
    [Google Scholar]
  131. 131.  Zempleni J 2017. Milk exosomes: beyond dietary microRNAs. Genes Nutr 12:12
    [Google Scholar]
  132. 132.  Askenase P 2018. Exosomes are the elephant in the room; their carrier effects likely influence target cells responses to miRNA transfers. eLife In press
    [Google Scholar]
  133. 133.  Guo Z, Karunatilaka KS, Rueda D 2009. Single-molecule analysis of protein-free U2-U6 snRNAs. Nat. Struct. Mol. Biol. 16:1154–59
    [Google Scholar]
  134. 134.  Maden BE, Hughes JM 1997. Eukaryotic ribosomal RNA: the recent excitement in the nucleotide modification problem. Chromosoma 105:391–400
    [Google Scholar]
  135. 135.  Reeves PG, Nielsen FH, Fahey GC Jr. 1993. AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet. J. Nutr. 123:1939–51
    [Google Scholar]
  136. 136.  Ward RE, Ninonuevo M, Mills DA, Lebrilla CB, German JB 2006. In vitro fermentation of breast milk oligosaccharides by Bifidobacterium infantis and Lactobacillus gasseri. Appl. Environ. Microbiol. 72:4497–99
    [Google Scholar]
  137. 137.  Mutai E, Zhou F, Zempleni J 2017. Depletion of dietary bovine milk exosomes impairs sensorimotor gating and spatial learning in C57BL/6 mice. FASEB J 31:150.4
    [Google Scholar]
  138. 138.  Duster R, Prickaerts J, Blokland A 2014. Purinergic signaling and hippocampal long-term potentiation. Curr. Neuropharmacol. 12:37–43
    [Google Scholar]
  139. 139.  Aguilar-Lozano A, Baier S, Grove R, Shu J, Giraud D et al. 2018. Concentrations of purine metabolites are elevated in fluids from adults and infants and in livers from mice fed diets depleted of bovine milk exosomes and their RNA cargos. J. Nutr. 148:121886–94
    [Google Scholar]
  140. 140.  Leiferman A, Shu J, Grove R, Cui J, Adamec J, Zempleni J 2018. A diet defined by its content of bovine milk exosomes and their RNA cargos has moderate effects on gene expression, amino acid profiles and grip strength in skeletal muscle in C57BL/6 mice. J. Nutr. Biochem 59:123–28
    [Google Scholar]
  141. 141.  Vilella F, Moreno-Moya JM, Balaguer N, Grasso A, Herrero M et al. 2015. Hsa-miR-30d, secreted by the human endometrium, is taken up by the pre-implantation embryo and might modify its transcriptome. Development 142:3210–21
    [Google Scholar]
  142. 142.  Sadri M, Xie F, Wood J, Zempleni J 2016. Dietary depletion of cow's milk microRNAs impairs fecundity in mice. FASEB J 30:673.5
    [Google Scholar]
  143. 143.  Panwala CM, Jones JC, Viney JL 1998. A novel model of inflammatory bowel disease: mice deficient for the multiple drug resistance gene, mdr1a, spontaneously develop colitis. J. Immunol. 161:5733–44
    [Google Scholar]
  144. 144.  Agrawal AK, Aqil F, Jeyabalan J, Spencer WA, Beck J et al. 2017. Milk-derived exosomes for oral delivery of paclitaxel. Nanomedicine 13:1627–36
    [Google Scholar]
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