Pasteurization of Human Milk Affects the MiRNA Cargo of EVs Decreasing Its Immunomodulatory Activity

Overview

Journal Sci Rep

Specialty Science

Date 2023 Jun 21

PMID 37344543

Authors

Monica F Torrez Lamberti

Leslie A Parker

Claudio F Gonzalez

Graciela L Lorca

Affiliations

Soon will be listed here.

Abstract

In this report, we evaluated the effect of the pasteurization (P) process of mother's own milk (MOM) on the miRNA content of extracellular vesicles (EVs) and its impact on innate immune responses. Differences in size or particle number were not observed upon pasteurization of MOM (PMOM). However, significant differences were observed in the EV membrane marker CD63 and miRNA profiles. miRNA sequencing identified 33 differentially enriched miRNAs between MOM and PMOM. These changes correlated with significant decreases in the ability of PMOM to modulate IL-8 secretion in intestinal Caco2 cells where only MOM were able to decrease IL-8 secretion in presence of TNFα. While EVs from MOM and PMOM were both able to induce a tolerogenic M2-like phenotype in THP-1 macrophages, a significant decrease in the transcript levels of IL-10 and RNA sensing genes was observed with PMOM. Together, our data indicates that pasteurization of MOM impacts the integrity and functionality of MOM, decreasing its EVs-mediated immunomodulatory activity. This data provides biomarkers that may be utilized during the optimization of milk processing to preserve its bioactivity.

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References

Aday S, Hazan-Halevy I, Chamorro-Jorganes A, Anwar M, Goldsmith M, Beazley-Long N . Bioinspired artificial exosomes based on lipid nanoparticles carrying let-7b-5p promote angiogenesis in vitro and in vivo. Mol Ther. 2021; 29(7):2239-2252. PMC: 8261169. DOI: 10.1016/j.ymthe.2021.03.015. View

Melnik B . The pathogenic role of persistent milk signaling in mTORC1- and milk-microRNA-driven type 2 diabetes mellitus. Curr Diabetes Rev. 2015; 11(1):46-62. PMC: 4428476. DOI: 10.2174/1573399811666150114100653. View

Nordgren T, Heires A, Zempleni J, Swanson B, Wichman C, Romberger D . Bovine milk-derived extracellular vesicles enhance inflammation and promote M1 polarization following agricultural dust exposure in mice. J Nutr Biochem. 2018; 64:110-120. PMC: 6363837. DOI: 10.1016/j.jnutbio.2018.10.017. View

Benmoussa A, Diallo I, Salem M, Michel S, Gilbert C, Sevigny J . Concentrates of two subsets of extracellular vesicles from cow's milk modulate symptoms and inflammation in experimental colitis. Sci Rep. 2019; 9(1):14661. PMC: 6787204. DOI: 10.1038/s41598-019-51092-1. View

Chesler D, Reiss C . The role of IFN-gamma in immune responses to viral infections of the central nervous system. Cytokine Growth Factor Rev. 2002; 13(6):441-54. DOI: 10.1016/s1359-6101(02)00044-8. View

Mueller N, Bakacs E, Combellick J, Grigoryan Z, Dominguez-Bello M . The infant microbiome development: mom matters. Trends Mol Med. 2015; 21(2):109-17. PMC: 4464665. DOI: 10.1016/j.molmed.2014.12.002. View

Matsushima K, Yang D, Oppenheim J . Interleukin-8: An evolving chemokine. Cytokine. 2022; 153:155828. DOI: 10.1016/j.cyto.2022.155828. View

Asztalos E . Supporting Mothers of Very Preterm Infants and Breast Milk Production: A Review of the Role of Galactogogues. Nutrients. 2018; 10(5). PMC: 5986480. DOI: 10.3390/nu10050600. View

Baier S, Nguyen C, Xie F, Wood J, 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(10):1495-500. PMC: 4162473. DOI: 10.3945/jn.114.196436. View

10.

Kim V, Han J, Siomi M . Biogenesis of small RNAs in animals. Nat Rev Mol Cell Biol. 2009; 10(2):126-39. DOI: 10.1038/nrm2632. View

11.

Hirano T, Ishihara K, Hibi M . Roles of STAT3 in mediating the cell growth, differentiation and survival signals relayed through the IL-6 family of cytokine receptors. Oncogene. 2000; 19(21):2548-56. DOI: 10.1038/sj.onc.1203551. View

12.

Yunna C, Mengru H, Lei W, Weidong C . Macrophage M1/M2 polarization. Eur J Pharmacol. 2020; 877:173090. DOI: 10.1016/j.ejphar.2020.173090. View

13.

Davies L, Jenkins S, Allen J, Taylor P . Tissue-resident macrophages. Nat Immunol. 2013; 14(10):986-95. PMC: 4045180. DOI: 10.1038/ni.2705. View

14.

Mecocci S, De Paolis L, Fruscione F, Pietrucci D, De Ciucis C, Dei Giudici S . In vitro evaluation of immunomodulatory activities of goat milk Extracellular Vesicles (mEVs) in a model of gut inflammation. Res Vet Sci. 2022; 152:546-556. DOI: 10.1016/j.rvsc.2022.09.021. View

15.

Espinosa-Martos I, Montilla A, de Segura A, Escuder D, Bustos G, Pallas C . Bacteriological, biochemical, and immunological modifications in human colostrum after Holder pasteurisation. J Pediatr Gastroenterol Nutr. 2013; 56(5):560-8. DOI: 10.1097/MPG.0b013e31828393ed. View

16.

Chang J, Chen C, Fang L, Tsai C, Chang Y, Wang T . Influence of prolonged storage process, pasteurization, and heat treatment on biologically-active human milk proteins. Pediatr Neonatol. 2013; 54(6):360-6. DOI: 10.1016/j.pedneo.2013.03.018. View

17.

Riedemann J, Macaulay V . IGF1R signalling and its inhibition. Endocr Relat Cancer. 2007; 13 Suppl 1:S33-43. DOI: 10.1677/erc.1.01280. View

18.

Cortez J, Makker K, Kraemer D, Neu J, Sharma R, Hudak M . Maternal milk feedings reduce sepsis, necrotizing enterocolitis and improve outcomes of premature infants. J Perinatol. 2017; 38(1):71-74. DOI: 10.1038/jp.2017.149. View

19.

Budagian V, Bulanova E, Paus R, Bulfone-Paus S . IL-15/IL-15 receptor biology: a guided tour through an expanding universe. Cytokine Growth Factor Rev. 2006; 17(4):259-80. DOI: 10.1016/j.cytogfr.2006.05.001. View

20.

. Donor Human Milk for the High-Risk Infant: Preparation, Safety, and Usage Options in the United States. Pediatrics. 2016; 139(1). DOI: 10.1542/peds.2016-3440. View