Circulating microRNAs in Breast Milk and Their Potential Impact on the Infant
Abstract
:1. Introduction
Components of Human Breast Milk: Nutrients and miRNAs
2. Transport and Absorption of Breast-Milk-Derived miRNAs
2.1. Mechanisms of miRNA to Resist Degradation
2.2. Presence of miRNA in the Digestive System, Absorption, and Biological Effect
3. Potential Effects of miRNA Found in Human Breast Milk
4. Evidence about the Influence of Milk Exosome-Derived miRNAs in Intestinal Maturation and Inflammation: Inflammatory Bowel Disease and Necrotizing Enterocolitis
5. Influence of the Diet and Other Maternal Factors in the Composition of miRNAs in Breast Milk
6. Potential Limitations and Controversies
7. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
- Król, J.; Loedige, I.; Filipowicz, W. The Widespread Regulation of MicroRNA Biogenesis, Function and Decay. Nat. Rev. Genet. 2010, 11, 597–610. [Google Scholar] [CrossRef] [PubMed]
- Alsaweed, M.; Hartmann, P.E.; Donna, G.; Kakulas, F. MicroRNAs in Breastmilk and the Lactating Breast: Potential Immunoprotectors and Developmental Regulators for the Infant and the Mother. Int. J. Environ. Res. Public Health 2015, 12, 13981–14020. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Turchinovich, A.; Burwinkel, B. Distinct AGO1 and AGO2 associated miRNA Profiles in Human Cells and Blood Plasma. RNA Biol. 2012, 9, 1066–1075. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sun, H.-Z.; Chen, Y.; Guan, L. MicroRNA Expression Profiles Across Blood and Different Tissues in Cattle. Sci. Data 2019, 6, 190013. [Google Scholar] [CrossRef] [PubMed]
- Chen, X.; Liang, H.; Zhang, J.; Zen, K.; Zhang, C.-Y. Secreted MicroRNAs: A New Form of Intercellular Communication. Trends Cell Boil. 2012, 22, 125–132. [Google Scholar] [CrossRef] [PubMed]
- Weber, J.A.; Baxter, D.H.; Zhang, S.; Huang, D.Y.; Huang, K.-H.; Lee, M.-J.; Galas, D.J.; Wang, K. The MicroRNA Spectrum in 12 Body Fluids. Clin. Chem. 2010, 56, 1733–1741. [Google Scholar] [CrossRef] [PubMed]
- Arroyo, J.D.; Chevillet, J.R.; Kroh, E.M.; Ruf, I.K.; Pritchard, C.C.; Gibson, D.F.; Mitchell, P.S.; Bennett, C.F.; Pogosova-Agadjanyan, E.L.; Stirewalt, D.L.; et al. Argonaute2 Complexes Carry a Population of Circulating MicroRNAs Independent of Vesicles in Human Plasma. Proc. Natl. Acad. Sci. USA 2011, 108, 5003–5008. [Google Scholar] [CrossRef] [Green Version]
- Pritchard, C.C.; Cheng, H.H.; Tewari, M. MicroRNA Profiling: Approaches and Considerations. Nat. Rev. Genet. 2012, 13, 358–369. [Google Scholar] [CrossRef]
- Riffo-Campos, A.L.; Riquelme, I.; Brebi, P. Tools for Sequence-Based miRNA Target Prediction: What to Choose? Int. J. Mol. Sci. 2016, 17, 1987. [Google Scholar] [CrossRef] [Green Version]
- Friedman, R.C.; Farh, K.K.-H.; Burge, C.B.; Bartel, B. Most Mammalian mRNAs are Conserved Targets of MicroRNAs. Genome Res. 2008, 19, 92–105. [Google Scholar] [CrossRef] [Green Version]
- Kakimoto, Y.; Matsushima, Y.; Tanaka, M.; Hayashi, H.; Wang, T.; Yokoyama, K.; Ochiai, E.; Osawa, M. MicroRNA Profiling of Gastric Content From Breast-Fed and Formula-Fed Infants to Estimate Last Feeding: A Pilot Study. Int. J. Leg. Med. 2019, 134, 903–909. [Google Scholar] [CrossRef] [PubMed]
- Munagala, R.; Aqil, F.; Jeyabalan, J.; Gupta, R. Bovine Milk-Derived Exosomes for Drug Delivery. Cancer Lett. 2016, 371, 48–61. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, J.; Zhang, F.; Didelot, X.; Bruce, K.D.; Cagampang, F.R.; Vatish, M.; Hanson, M.A.; Lehnert, H.; Ceriello, A.; Byrne, C.D. Maternal High Fat Diet During Pregnancy and Lactation Alters Hepatic Expression of Insulin Like Growth Factor-2 and Key MicroRNAs in the Adult Offspring. BMC Genom. 2009, 10, 478. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tomé-Carneiro, J.; Fernández-Alonso, N.; Tomás-Zapico, C.; Visioli, F.; Iglesias-Gutierrez, E.; Dávalos, A. Breast Milk MicroRNAs Harsh Journey Towards Potential Effects in Infant Development and Maturation. Lipid Encapsulation Can Help. Pharmacol. Res. 2018, 132, 21–32. [Google Scholar] [CrossRef] [PubMed]
- Wang, L.; Sadri, M.; Giraud, D.; Zempleni, J. 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. 2018, 148, 153–159. [Google Scholar] [CrossRef] [Green Version]
- Sanwlani, R.; Fonseka, P.; Chitti, S.V.; Mathivanan, S. Milk-Derived Extracellular Vesicles in Inter-Organism, Cross-Species Communication and Drug Delivery. Proteomes 2020, 8, 11. [Google Scholar] [CrossRef]
- Cintio, M.; Polacchini, G.; Scarsella, E.; Montanari, T.; Stefanon, B.; Colitti, M. MicroRNA Milk Exosomes: From Cellular Regulator to Genomic Marker. Animals 2020, 10, 1126. [Google Scholar] [CrossRef]
- Victora, C.G.; Bahl, R.; Barros, A.J.D.; França, G.V.A.; Horton, S.E.; Krasevec, J.; Murch, S.; Sankar, M.J.; Walker, N.; Rollins, N.C.; et al. Breastfeeding in the 21st Century: Epidemiology, Mechanisms, and Lifelong Effect. Lancet 2016, 387, 475–490. [Google Scholar] [CrossRef] [Green Version]
- Zhou, Q.; Li, M.; Wang, X.; Li, Q.; Wang, T.; Zhu, Q.; Zhou, X.; Wang, X.; Gao, X.; Li, X. Immune-Related MicroRNAs are Abundant in Breast Milk Exosomes. Int. J. Biol. Sci. 2011, 8, 118–123. [Google Scholar] [CrossRef]
- Izumi, H.; Tsuda, M.; Sato, Y.; Kosaka, N.; Ochiya, T.; Iwamoto, H.; Namba, K.; Takeda, Y. Bovine Milk Exosomes Contain MicroRNA and MRNA and Are Taken up by Human Macrophages. J. Dairy Sci. 2015, 98, 2920–2933. [Google Scholar] [CrossRef] [Green Version]
- Kim, S.Y.; Yi, D.Y. Components of Human Breast Milk: From Macronutrient to Microbiome and MicroRNA. Clin. Exp. Pediatr. 2020, 63, 301–309. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Andreas, N.J.; Kampmann, B.; Le Doaré, K. Human Breast Milk: A Review on Its Composition and Bioactivity. Early Hum. Dev. 2015, 91, 629–635. [Google Scholar] [CrossRef] [PubMed]
- Ballard, O.; Morrow, A.L. Human Milk Composition. Pediatr. Clin. North Am. 2013, 60, 49–74. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Alsaweed, M.; Ching-Tat, L.; Hartmann, P.E.; Donna, G.; Kakulas, F. Human Milk Cells Contain Numerous miRNAs that May Change with Milk Removal and Regulate Multiple Physiological Processes. Int. J. Mol. Sci. 2016, 17, 956. [Google Scholar] [CrossRef] [Green Version]
- Golan-Gerstl, R.; Reif, S.; Shiff, Y.E.; Moshayoff, V.; Schecter, D.; Leshkowitz, D. Characterization and Biological Function of Milk-Derived miRNAs. Mol. Nutr. Food Res. 2017, 61, 1700009. [Google Scholar] [CrossRef]
- Van Herwijnen, M.J.C.; Driedonks, T.; Snoek, B.L.; Kroon, A.M.T.; Kleinjan, M.; Jorritsma, R.; Pieterse, C.M.J.; Hoen, E.N.M.N.-‘T.; Wauben, M.H.M. Abundantly Present miRNAs in Milk-Derived Extracellular Vesicles Are Conserved Between Mammals. Front. Nutr. 2018, 5. [Google Scholar] [CrossRef]
- Alsaweed, M.; Ching-Tat, L.; Hartmann, P.E.; Geddes, D.T.; Kakulas, F. Human Milk Cells and Lipids Conserve Numerous Known and Novel miRNAs, Some of Which Are Differentially Expressed during Lactation. PLoS ONE 2016, 11, e0152610. [Google Scholar] [CrossRef] [Green Version]
- Rubio, M.; Bustamante, M.; Hernandez-Ferrer, C.; Fernandez-Orth, D.; Pantano, L.; Sarria, Y.; Piqué-Borras, M.; Vellvé, K.; Agramunt, S.; Carreras, R.; et al. Circulating miRNAs, isomiRs and Small RNA Clusters in Human Plasma and Breast Milk. PLoS ONE 2018, 13, e0193527. [Google Scholar] [CrossRef]
- Zeng, B.; Chen, T.; Luo, J.; Xie, M.; Wei, L.; Xi, Q.; Sun, J.; Zhang, Y. Exploration of Long Non-coding RNAs and Circular RNAs in Porcine Milk Exosomes. Front. Genet. 2020, 11, 652. [Google Scholar] [CrossRef]
- Title, A.C.; Denzler, R.; Stoffel, M. Uptake and Function Studies of Maternal Milk-derived MicroRNAs. J. Boil. Chem. 2015, 290, 23680–23691. [Google Scholar] [CrossRef] [Green Version]
- Valadi, H.; Ekström, K.; Bossios, A.; Sjöstrand, M.; Lee, J.J.; Lötvall, J. Exosome-Mediated Transfer of MRNAs and MicroRNAs Is a Novel Mechanism of Genetic Exchange Between Cells. Nat. Cell Biol. 2007, 9, 654–659. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Admyre, C.; Johansson, S.M.; Qazi, K.R.; Filén, J.-J.; Lahesmaa, R.; Norman, M.; Neve, E.P.A.; Scheynius, A.; Gabrielsson, S. Exosomes with Immune Modulatory Features Are Present in Human Breast Milk. J. Immunol. 2007, 179, 1969–1978. [Google Scholar] [CrossRef]
- Lässer, C.; Alikhani, V.S.; Ekström, K.; Eldh, M.; Paredes, P.T.; Bossios, A.; Sjöstrand, M.; Gabrielsson, S.; Lötvall, J.; Valadi, H. Human Saliva, Plasma and Breast Milk Exosomes Contain RNA: Uptake by Macrophages. J. Transl. Med. 2011, 9, 9. [Google Scholar] [CrossRef] [Green Version]
- Le Doaré, K.; Holder, B.; Bassett, A.; Pannaraj, P.S. Mother’s Milk: A Purposeful Contribution to the Development of the Infant Microbiota and Immunity. Front. Immunol. 2018, 9. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hata, T.; Murakami, K.; Nakatani, H.; Yamamoto, Y.; Matsuda, T.; Aoki, N. Isolation of Bovine Milk-Derived Microvesicles Carrying MRNAs and MicroRNAs. Biochem. Biophys. Res. Commun. 2010, 396, 528–533. [Google Scholar] [CrossRef] [PubMed]
- Izumi, H.; Kosaka, N.; Shimizu, T.; Sekine, K.; Ochiya, T.; Takase, M. Bovine Milk Contains MicroRNA and Messenger RNA That Are Stable Under Degradative Conditions. J. Dairy Sci. 2012, 95, 4831–4841. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lin, D.; Chen, T.; Xie, M.; Li, M.; Zeng, B.; Sun, R.; Zhu, Y.; Ye, D.; Wu, J.; Sun, J.; et al. Oral Administration of Bovine and Porcine Milk Exosome Alter miRNAs Profiles in Piglet Serum. Sci. Rep. 2020, 10, 1–11. [Google Scholar] [CrossRef]
- Wang, K.; Zhang, S.; Weber, J.; Baxter, D.; Galas, D.J. Export of MicroRNAs and MicroRNA-Protective Protein by Mammalian Cells. Nucleic Acids Res. 2010, 38, 7248–7259. [Google Scholar] [CrossRef] [Green Version]
- Vickers, K.C.; Palmisano, B.T.; Shoucri, B.M.; Shamburek, R.D.; Remaley, A.T. MicroRNAs are Transported in Plasma and Delivered to Recipient Cells by High-Density Lipoproteins. Nat. Cell Biol. 2011, 13, 423–433. [Google Scholar] [CrossRef] [Green Version]
- Smyczynska, U.; Bartlomiejczyk, M.A.; Stanczak, M.M.; Sztromwasser, P.; Wesolowska, A.; Barbarska, O.; Pawlikowska, E.; Fendler, W. Impact of Processing Method on Donated Human Breast Milk MicroRNA Content. PLoS ONE 2020, 15, e0236126. [Google Scholar] [CrossRef]
- Melnik, B.C.; Kakulas, F.; Donna, G.; Hartmann, P.E.; John, S.M.; Carrera-Bastos, P.; Cordain, L.; Schmitz, G. Milk miRNAs: Simple Nutrients or Systemic Functional Regulators? Nutr. Metab. 2016, 13, 42. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Liao, Y.; Du, X.; Li, J.; Lönnerdal, B. Human Milk Exosomes and Their MicroRNAs Survive Digestion In Vitro and Are Taken up by Human Intestinal Cells. Mol. Nutr. Food Res. 2017, 61, 1700082. [Google Scholar] [CrossRef] [PubMed]
- Baier, S.R.; Nguyen, C.; Xie, F.; Wood, J.R.; Zempleni, J. MicroRNAs are Absorbed in Biologically Meaningful Amounts From Nutritionally Relevant Doses of Cow Milk and Affect Gene Expression in Peripheral Blood Mononuclear Cells, HEK-293 Kidney Cell Cultures, and Mouse Livers. J. Nutr. 2014, 144, 1495–1500. [Google Scholar] [CrossRef] [PubMed]
- Kusuma, R.J.; Manca, S.; Friemel, T.; Sukreet, S.; Nguyen, C.; Zempleni, J. Human Vascular Endothelial Cells Transport Foreign Exosomes from Cow’s Milk by Endocytosis. Am. J. Physiol. Cell Physiol. 2016, 310, 6–7. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Manca, S.; Upadhyaya, B.; Mutai, E.; Desaulniers, A.T.; Cederberg, R.A.; White, B.R.; Zempleni, J. Milk Exosomes Are Bioavailable and Distinct MicroRNA Cargos Have Unique Tissue Distribution Patterns. Sci. Rep. 2018, 8, 11321. [Google Scholar] [CrossRef] [Green Version]
- Kosaka, N.; Izumi, H.; Sekine, K.; Ochiya, T. MicroRNA as a New Immune-Regulatory Agent in Breast Milk. Silence 2010, 1, 7. [Google Scholar] [CrossRef] [Green Version]
- Auerbach, A.; Vyas, G.; Li, A.; Halushka, M.; Witwer, K.W. Uptake of Dietary Milk miRNAs by Adult Humans: A Validation Study. F1000 Res. 2016, 5, 721. [Google Scholar] [CrossRef]
- Laubier, J.; Castille, J.; Le Guillou, S.; Le Provost, F. No Effect of an Elevated miR-30b Level in Mouse Milk on Its Level in Pup Tissues. RNA Biol. 2015, 12, 26–29. [Google Scholar] [CrossRef]
- Betker, J.L.; Angle, B.M.; Graner, M.W.; Anchordoquy, T.J. The Potential of Exosomes from Cow Milk for Oral Delivery. J. Pharm. Sci. 2019, 108, 1496–1505. [Google Scholar] [CrossRef]
- Reif, S.; Elbaum-Shiff, Y.; Golan-Gerstl, R. Milk-Derived Exosomes (MDEs) Have a Different Biological Effect on Normal Fetal Colon Epithelial Cells Compared to Colon Tumor Cells in a miRNA-Dependent Manner. J. Transl. Med. 2019, 17, 325. [Google Scholar] [CrossRef]
- Ventura, A.; Young, A.G.; Winslow, M.M.; Lintault, L.; Meissner, A.; Erkeland, S.J.; Newman, J.; Bronson, R.T.; Crowley, D.; Stone, J.R.; et al. Targeted Deletion Reveals Essential and Overlapping Functions of the miR-17∼92 Family of miRNA Clusters. Cell 2008, 132, 875–886. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Johnnidis, J.B.; Harris, M.H.; Wheeler, R.T.; Stehling-Sun, S.; Lam, M.H.; Kirak, O.; Brummelkamp, T.R.; Fleming, M.D.; Camargo, F.D. Regulation of Progenitor Cell Proliferation and Granulocyte Function by MicroRNA-223. Nature 2008, 451, 1125–1129. [Google Scholar] [CrossRef] [PubMed]
- Zhou, B.; Wang, S.; Mayr, C.; Bartel, D.P.; Lodish, H.F. miR-150, a MicroRNA Expressed in Mature B and T Cells, Blocks Early B Cell Development When Expressed Prematurely. Proc. Natl. Acad. Sci. USA 2007, 104, 7080–7085. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gaziel-Sovran, A.; Lizcano, J.M.; Di Micco, R.; Collins, M.K.; Hanniford, D.; De Miera, E.V.-S.; Rakus, J.F.; Dankert, J.F.; Shang, S.; Kerbel, R.S.; et al. miR-30b/30d Regulation of GalNAc Transferases Enhances Invasion and Immunosuppression during Metastasis. Cancer Cell 2011, 20, 104–118. [Google Scholar] [CrossRef] [Green Version]
- Stittrich, A.-B.; Haftmann, C.; Sgouroudis, E.; Kühl, A.A.; Hegazy, A.N.; Panse, I.; Riedel, R.; Flossdorf, M.; Dong, J.; Fuhrmann, F.; et al. The MicroRNA miR-182 Is Induced by IL-2 and Promotes Clonal Expansion of Activated Helper T Lymphocytes. Nat. Immunol. 2010, 11, 1057–1062. [Google Scholar] [CrossRef] [Green Version]
- Melnik, B.C. The Potential Mechanistic Link between Allergy and Obesity Development and Infant Formula Feeding. Allergy Asthma Immunol. 2014, 10, 37. [Google Scholar] [CrossRef] [Green Version]
- Kohlhaas, S.; Garden, O.A.; Scudamore, C.; Turner, M.; Okkenhaug, K.; Vigorito, E. Cutting Edge: The Foxp3 Target miR-155 Contributes to the Development of Regulatory T Cells. J. Immunol. 2009, 182, 2578–2582. [Google Scholar] [CrossRef]
- Lu, L.-F.; Thai, T.-H.; Calado, D.P.; Chaudhry, A.; Kubo, M.; Tanaka, K.; Loeb, G.B.; Lee, H.; Yoshimura, A.; Rajewsky, K.; et al. Foxp3-Dependent MicroRNA155 Confers Competitive Fitness to Regulatory T Cells by Targeting SOCS1 Protein. Immunity 2009, 30, 80–91. [Google Scholar] [CrossRef] [Green Version]
- Melnik, B.C.; John, S.M.; Schmitz, G. Milk: An Exosomal MicroRNA Transmitter Promoting Thymic Regulatory T Cell Maturation Preventing the Development of Atopy? J. Transl. Med. 2014, 12, 43. [Google Scholar] [CrossRef] [Green Version]
- Sozanska, B.; Pearce, N.; Dudek, K.; Cullinan, P. Consumption of Unpasteurized Milk and Its Effects on Atopy and Asthma in Children and Adult Inhabitants in Rural Poland. Allergy Eur. J. Allergy-Clin. Immunol. 2013, 68, 644–650. [Google Scholar] [CrossRef]
- Melnik, B.C. Milk Exosomal miRNAs: Potential Drivers of AMPK-to-mTORC1 Switching in β-cell de-Differentiation of Type 2 Diabetes Mellitus. Nutr. Metab. 2019, 16, 1–13. [Google Scholar] [CrossRef] [PubMed]
- Olkkonen, V.M.; Levine, T.P. Oxysterol Binding Proteins: In More Than One Place at One Time? Biochem. Cell Biol. 2004, 82, 87–98. [Google Scholar] [CrossRef] [PubMed]
- Sun, L.; Xie, H.; Mori, M.A.; Alexander, R.; Yuan, B.; Hattangadi, S.M.; Liu, Q.; Kahn, C.R.; Lodish, H.F. Mir193b–365 is Essential for Brown Fat Differentiation. Nat. Cell Biol. 2011, 13, 958–965. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Aksoy-Aksel, A.; Ezampa, F.; Eschratt, G. MicroRNAs and Synaptic Plasticity—A Mutual Relationship. Philos. Trans. R. Soc. B Biol. Sci. 2014, 369, 20130515. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lönnerdal, B. Human Milk MicroRNAs/Exosomes: Composition and Biological Effects. Nestle Nutr. Inst. Work. 2019, 90, 83–92. [Google Scholar] [CrossRef]
- Melnik, B.C.; Schmitz, G. Milk’s Role as an Epigenetic Regulator in Health and Disease. Diseases 2017, 5, 12. [Google Scholar] [CrossRef]
- Lin, X.; Luo, J.; Zhang, L.; Wang, W.; Gou, D. MiR-103 Controls Milk Fat Accumulation in Goat (Capra Hircus) Mammary Gland during Lactation. PLoS ONE 2013, 8, e79258. [Google Scholar] [CrossRef] [Green Version]
- Reif, S.; Elbaum-Shiff, Y.; Koroukhov, N.; Shilo, I.; Musseri, M.; Golan-Gerstl, R. Cow and Human Milk-Derived Exosomes Ameliorate Colitis in DSS Murine Model. Nutrients 2020, 12, 2589. [Google Scholar] [CrossRef]
- Benmoussa, A.; Diallo, I.; Salem, M.; Michel, S.; Gilbert, C.; Sévigny, J.; Provost, P. Concentrates of Two Subsets of Extracellular Vesicles From Cow’s Milk Modulate Symptoms and Inflammation in Experimental Colitis. Sci. Rep. 2019, 9, 14661. [Google Scholar] [CrossRef] [Green Version]
- Stremmel, W.; Weiskirchen, R.; Melnik, B.C. Milk Exosomes Prevent Intestinal Inflammation in a Genetic Mouse Model of Ulcerative Colitis: A Pilot Experiment. Inflamm. Intest. Dis. 2020, 5, 1–7. [Google Scholar] [CrossRef]
- Xie, M.-Y.; Chen, T.; Xi, Q.-Y.; Hou, L.-J.; Luo, J.-Y.; Zeng, B.; Li, M.; Sun, J.; Zhang, Y. Porcine Milk Exosome miRNAs Protect Intestinal Epithelial Cells Against Deoxynivalenol-Induced Damage. Biochem. Pharmacol. 2020, 175, 113898. [Google Scholar] [CrossRef] [PubMed]
- Galley, J.D.; Besner, G.E. The Therapeutic Potential of Breast Milk-Derived Extracellular Vesicles. Nutrients 2020, 12, 745. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pisano, C.; Galley, J.; Elbahrawy, M.; Wang, Y.; Farrell, A.; Brigstock, D.; Besner, G.E. Human Breast Milk-Derived Extracellular Vesicles in the Protection Against Experimental Necrotizing Enterocolitis. J. Pediatr. Surg. 2019, 55, 54–58. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Li, B.; Hock, A.; Wu, R.Y.; Minich, A.; Botts, S.R.; Lee, C.; Antounians, L.; Miyake, H.; Koike, Y.; Chen, Y.; et al. Bovine Milk-Derived Exosomes Enhance Goblet Cell Activity and Prevent the Development of Experimental Necrotizing Enterocolitis. PLoS ONE 2019, 14, e0211431. [Google Scholar] [CrossRef]
- Bravi, F.; Wiens, F.; DeCarli, A.; Pont, A.D.; Agostoni, C.; Ferraroni, M. Impact of Maternal Nutrition on Breast-Milk Composition: A Systematic Review. Am. J. Clin. Nutr. 2016, 104, 646–662. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Segura, S.A.; Arena, J.; Materna, D.L.; Asociación Espanola de Pediatria. The Importance of Maternal Nutrition During Breastfeeding: Do Breastfeeding Mothers Need Nutritional Supplements? An. Pediatr. 2016, 84, 347. [Google Scholar]
- Panagos, P.G.; Vishwanathan, R.; Penfield-Cyr, A.; Matthan, N.R.; Shivappa, N.; Wirth, M.D.; Hebert, J.R.; Sen, S. Breastmilk From Obese Mothers Has Pro-Inflammatory Properties and Decreased Neuroprotective Factors. J. Perinatol. 2016, 36, 284–290. [Google Scholar] [CrossRef] [Green Version]
- Fujimori, M.; França, E.L.; Fiorin, V.; Morais, T.C.; Honorio-França, A.C.; De Abreu, L.C. Changes in the Biochemical and Immunological Components of Serum and Colostrum of Overweight and Obese Mothers. BMC Pregnancy Childbirth 2015, 15, 166. [Google Scholar] [CrossRef]
- Pomar, C.A.; Castro, H.; Picó, C.; Serra, F.; Palou, A.; Sánchez, J. Cafeteria Diet Consumption during Lactation in Rats, Rather than Obesity Per Se, Alters miR-222, miR-200a, and miR-26a Levels in Milk. Mol. Nutr. Food Res. 2019, 63, e1800928. [Google Scholar] [CrossRef]
- Pomar, C.A.; Sánchez, J.; Palou, A. The Intake of a Cafeteria Diet in Nursing Rats Alters the Breast Milk Concentration of Proteins Important for the Development of Offspring. Nutrients 2020, 12, 2470. [Google Scholar] [CrossRef]
- Munch, E.M.; Harris, R.A.; Mohammad, M.A.; Benham, A.L.; Pejerrey, S.M.; Showalter, L.; Hu, M.; Shope, C.D.; Maningat, P.D.; Gunaratne, P.H.; et al. Transcriptome Profiling of microRNA by Next-Gen Deep Sequencing Reveals Known and Novel miRNA Species in the Lipid Fraction of Human Breast Milk. PLoS ONE 2013, 8, e50564. [Google Scholar] [CrossRef] [PubMed]
- Xi, Y.; Jiang, X.; Li, R.; Chen, M.; Song, W.; Li, X. The Levels of Human Milk MicroRNAs and Their Association with Maternal Weight Characteristics. Eur. J. Clin. Nutr. 2015, 70, 445–449. [Google Scholar] [CrossRef] [PubMed]
- Zamanillo, R.; Sánchez, J.; Serra, F.; Palou, A. Breast Milk Supply of MicroRNA Associated with Leptin and Adiponectin Is Affected by Maternal Overweight/Obesity and Influences Infancy BMI. Nutrients 2019, 11, 2589. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mirza, A.H.; Kaur, S.; Nielsen, L.B.; Størling, J.; Yarani, R.; Roursgaard, M.; Mathiesen, E.R.; Damm, P.; Svare, J.; Mortensen, H.B.; et al. Breast Milk-Derived Extracellular Vesicles Enriched in Exosomes from Mothers With Type 1 Diabetes Contain Aberrant Levels of microRNAs. Front. Immunol. 2019, 10, 10. [Google Scholar] [CrossRef]
- Witwer, K.W. Circulating MicroRNA Biomarker Studies: Pitfalls and Potential Solutions. Clin. Chem. 2015, 61, 56–63. [Google Scholar] [CrossRef]
- Wang, J.; Chen, J.; Sen, S. MicroRNA as Biomarkers and Diagnostics. J. Cell. Physiol. 2015, 231, 25–30. [Google Scholar] [CrossRef]
miRNA | Functions | Reference |
---|---|---|
miR-181, miR-155 | Differentiation of B cells. | [46] |
miR17, miR92 | Regulation of monocyte development. Differentiation and maturation of T and B cells. | [51] |
miR-223 | Proliferation of granulocytes. | [52] |
miR-150 | Suppression of B cells. | [53] |
miR-200a-3p | Involved in Hodgkin lymphoma and oral cancers. | [19] |
miR-148a-3p | Negative regulation of immunity.Different roles in metabolism and development. | [19,41] |
miR-30b-5p | Immunosuppression. | [54] |
miR-182-5p | T-cell activation. Lactose synthesis in mammary gland. Regulation of UDP-glucose transporter (SLC2A3). | [56,24] |
miR-155 | Development of T-reg cells (TREG). | [58] |
miR-125-5p | Regulation of oxysterol-binding protein-related protein (ORP) 9, involved in lipid metabolism. | [62] |
miR-193b, 3iR-365 | Differentiation of brown adipose tissue. | [63] |
let-7f-5p | Lactose synthesis in mammary gland. Regulation of UDP-galactose transporter (SLC35A2). | [24] |
miR-103, miR-145 | Lipid synthesis in mammary gland. | [67] |
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Carrillo-Lozano, E.; Sebastián-Valles, F.; Knott-Torcal, C. Circulating microRNAs in Breast Milk and Their Potential Impact on the Infant. Nutrients 2020, 12, 3066. https://doi.org/10.3390/nu12103066
Carrillo-Lozano E, Sebastián-Valles F, Knott-Torcal C. Circulating microRNAs in Breast Milk and Their Potential Impact on the Infant. Nutrients. 2020; 12(10):3066. https://doi.org/10.3390/nu12103066
Chicago/Turabian StyleCarrillo-Lozano, Elena, Fernando Sebastián-Valles, and Carolina Knott-Torcal. 2020. "Circulating microRNAs in Breast Milk and Their Potential Impact on the Infant" Nutrients 12, no. 10: 3066. https://doi.org/10.3390/nu12103066