Biological Properties of Milk-Derived Extracellular Vesicles and Their Physiological Functions in Infant

Overview

Journal Front Cell Dev Biol

Specialty Cell Biology

Date 2021 Jul 12

PMID 34249944

Citations 39

Authors

Xue Jiang

Lianghui You

Zhenxing Zhang

Xianwei Cui

Hong Zhong

Xingzhen Sun

Chenbo Ji

Xia Chi

Affiliations

Soon will be listed here.

Abstract

Extracellular vesicles (EVs) are released by all cells under pathological and physiological conditions. EVs harbor various biomolecules, including protein, lipid, non-coding RNA, messenger RNA, and DNA. In 2007, mRNA and microRNA (miRNA) carried by EVs were found to have regulatory functions in recipient cells. The biological function of EVs has since then increasingly drawn interest. Breast milk, as the most important nutritional source for infants, contains EVs in large quantities. An increasing number of studies have provided the basis for the hypothesis associated with information transmission between mothers and infants via breast milk-derived EVs. Most studies on milk-derived EVs currently focus on miRNAs. Milk-derived EVs contain diverse miRNAs, which remain stable both and ; as such, they can be absorbed across different species. Further studies have confirmed that miRNAs derived from milk-derived EVs can resist the acidic environment and enzymatic hydrolysis of the digestive tract; moreover, they can be absorbed by intestinal cells in infants to perform physiological functions. miRNAs derived from milk EVs have been reported in the maturation of immune cells, regulation of immune response, formation of neuronal synapses, and development of metabolic diseases such as obesity and diabetes. This article reviews current status and advances in milk-derived EVs, including their history, biogenesis, molecular contents, and biological functions. The effects of milk-derived EVs on growth and development in both infants and adults were emphasized. Finally, the potential application and future challenges of milk-derived EVs were discussed, providing comprehensive understanding and new insight into milk-derived EVs.

Citing Articles

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References

Friedman R, Farh K, Burge C, Bartel D . Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. 2008; 19(1):92-105. PMC: 2612969. DOI: 10.1101/gr.082701.108. View

Modepalli V, Kumar A, Hinds L, Sharp J, Nicholas K, Lefevre C . Differential temporal expression of milk miRNA during the lactation cycle of the marsupial tammar wallaby (Macropus eugenii). BMC Genomics. 2014; 15:1012. PMC: 4247635. DOI: 10.1186/1471-2164-15-1012. View

Adriano B, Cotto N, Chauhan N, Jaggi M, Chauhan S, Yallapu M . Milk exosomes: Nature's abundant nanoplatform for theranostic applications. Bioact Mater. 2021; 6(8):2479-2490. PMC: 7856328. DOI: 10.1016/j.bioactmat.2021.01.009. View

Carney M, Tarasiuk A, DiAngelo S, Silveyra P, Podany A, Birch L . Metabolism-related microRNAs in maternal breast milk are influenced by premature delivery. Pediatr Res. 2017; 82(2):226-236. PMC: 5552431. DOI: 10.1038/pr.2017.54. View

Chen W, Chen X, Qian Y, Wang X, Zhou Y, Yan X . Lipidomic Profiling of Human Milk Derived Exosomes and Their Emerging Roles in the Prevention of Necrotizing Enterocolitis. Mol Nutr Food Res. 2021; 65(10):e2000845. DOI: 10.1002/mnfr.202000845. View

Del Pozo-Acebo L, Lopez de Las Hazas M, Tome-Carneiro J, Gil-Cabrerizo P, San-Cristobal R, Busto R . Bovine Milk-Derived Exosomes as a Drug Delivery Vehicle for miRNA-Based Therapy. Int J Mol Sci. 2021; 22(3). PMC: 7865385. DOI: 10.3390/ijms22031105. View

Xie M, Hou L, Sun J, Zeng B, Xi Q, Luo J . Porcine Milk Exosome MiRNAs Attenuate LPS-Induced Apoptosis through Inhibiting TLR4/NF-κB and p53 Pathways in Intestinal Epithelial Cells. J Agric Food Chem. 2019; 67(34):9477-9491. DOI: 10.1021/acs.jafc.9b02925. View

Andres A, Casey P, Cleves M, Badger T . Body fat and bone mineral content of infants fed breast milk, cow's milk formula, or soy formula during the first year of life. J Pediatr. 2013; 163(1):49-54. DOI: 10.1016/j.jpeds.2012.12.067. View

Zeng B, Chen T, Xie M, Luo J, He J, Xi Q . Exploration of long noncoding RNA in bovine milk exosomes and their stability during digestion in vitro. J Dairy Sci. 2019; 102(8):6726-6737. DOI: 10.3168/jds.2019-16257. View

10.

Shi C, Zhang M, Tong M, Yang L, Pang L, Chen L . miR-148a is Associated with Obesity and Modulates Adipocyte Differentiation of Mesenchymal Stem Cells through Wnt Signaling. Sci Rep. 2015; 5:9930. PMC: 4441322. DOI: 10.1038/srep09930. View

11.

Liao Y, Du X, Li J, Lonnerdal 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(11). DOI: 10.1002/mnfr.201700082. View

12.

Mohammad F, Mondal T, Guseva N, Pandey G, Kanduri C . Kcnq1ot1 noncoding RNA mediates transcriptional gene silencing by interacting with Dnmt1. Development. 2010; 137(15):2493-9. DOI: 10.1242/dev.048181. View

13.

Mi X, Xu R, Hong S, Xu T, Zhang W, Liu M . M2 Macrophage-Derived Exosomal lncRNA AFAP1-AS1 and MicroRNA-26a Affect Cell Migration and Metastasis in Esophageal Cancer. Mol Ther Nucleic Acids. 2020; 22:779-790. PMC: 7595846. DOI: 10.1016/j.omtn.2020.09.035. View

14.

Zhang Q, Cai R, Tang G, Zhang W, Pang W . MiR-146a-5p targeting SMAD4 and TRAF6 inhibits adipogenensis through TGF-β and AKT/mTORC1 signal pathways in porcine intramuscular preadipocytes. J Anim Sci Biotechnol. 2021; 12(1):12. PMC: 7856799. DOI: 10.1186/s40104-020-00525-3. View

15.

Sun J, Xiong J, Yao L, Chen T, Luo J, Xi Q . The effect of dietary ginseng polysaccharide supplementation on porcine milk-derived esRNAs involved in the host immune responses. J Anim Physiol Anim Nutr (Berl). 2018; 103(1):276-282. DOI: 10.1111/jpn.12993. View

16.

Ma S, Niu M, Hao Z, Liu M, Tong C, Zhao X . Selective packaged circular RNAs in milk extracellular vesicles during infection may have potential against bacterial infection. RNA Biol. 2020; 18(5):818-831. PMC: 8078504. DOI: 10.1080/15476286.2020.1853975. View

17.

Takata A, Otsuka M, Kojima K, Yoshikawa T, Kishikawa T, Yoshida H . MicroRNA-22 and microRNA-140 suppress NF-κB activity by regulating the expression of NF-κB coactivators. Biochem Biophys Res Commun. 2011; 411(4):826-31. DOI: 10.1016/j.bbrc.2011.07.048. View

18.

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(9). PMC: 7551078. DOI: 10.3390/nu12092589. View

19.

Lonnerdal B, Jiang R, Du X . Bovine lactoferrin can be taken up by the human intestinal lactoferrin receptor and exert bioactivities. J Pediatr Gastroenterol Nutr. 2011; 53(6):606-14. DOI: 10.1097/MPG.0b013e318230a419. View

20.

Wolf T, Baier S, Zempleni J . 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. 2015; 145(10):2201-6. PMC: 4580964. DOI: 10.3945/jn.115.218586. View