Title:	Exosome-Derived MicroRNAs of Human Milk and Their Effects on Infant Health and Development
Authors:	Melnik, Bodo C. Stremmel, Wolfgang Weiskirchen, Ralf John, Swen Malte Schmitz, Gerd
ORCID of the author:	https://orcid.org/0000-0002-4501-1809 https://orcid.org/0000-0002-1325-1007 https://orcid.org/0000-0003-3888-0931 https://orcid.org/0000-0001-5406-9458
Abstract:	Multiple biologically active components of human milk support infant growth, health and development. Milk provides a wide spectrum of mammary epithelial cell-derived extracellular vesicles (MEVs) for the infant. Although the whole spectrum of MEVs appears to be of functional importance for the growing infant, the majority of recent studies report on the MEV subfraction of milk exosomes (MEX) and their miRNA cargo, which are in the focus of this review. MEX and the dominant miRNA-148a play a key role in intestinal maturation, barrier function and suppression of nuclear factor-κB (NF-κB) signaling and may thus be helpful for the prevention and treatment of necrotizing enterocolitis. MEX and their miRNAs reach the systemic circulation and may impact epigenetic programming of various organs including the liver, thymus, brain, pancreatic islets, beige, brown and white adipose tissue as well as bones. Translational evidence indicates that MEX and their miRNAs control the expression of global cellular regulators such as DNA methyltransferase 1—which is important for the up-regulation of developmental genes including insulin, insulin-like growth factor-1, α-synuclein and forkhead box P3—and receptor-interacting protein 140, which is important for the regulation of multiple nuclear receptors. MEX-derived miRNA-148a and miRNA-30b may stimulate the expression of uncoupling protein 1, the key inducer of thermogenesis converting white into beige/brown adipose tissue. MEX have to be considered as signalosomes derived from the maternal lactation genome emitted to promote growth, maturation, immunological and metabolic programming of the offspring. Deeper insights into milk’s molecular biology allow the conclusion that infants are both “breast-fed” and “breast-programmed”. In this regard, MEX miRNA-deficient artificial formula is not an adequate substitute for breastfeeding, the birthright of all mammals.
Citations:	Melnik, B.C.; Stremmel, W.; Weiskirchen, R.; John, S.M.; Schmitz, G. (2021): Exosome-Derived MicroRNAs of Human Milk and Their Effects on Infant Health and Development. Biomolecules, 11, 851.
URL:	https://doi.org/10.48693/37 https://osnadocs.ub.uni-osnabrueck.de/handle/ds-202202076042
Subject Keywords:	adipogenesis; DNA methyltransferase 1; immune tolerance; intestinal maturation; milk exosome; milk miRNAs; necrotizing enterocolitis; nuclear factor-κB; receptor-interacting protein 140; systemic milk effects
Issue Date:	7-Jun-2021
License name:	Attribution 4.0 International
License url:	http://creativecommons.org/licenses/by/4.0/
Type of publication:	Einzelbeitrag in einer wissenschaftlichen Zeitschrift [article]
Appears in Collections:	FB08 - Hochschulschriften Open-Access-Publikationsfonds

This item is licensed under a Creative Commons License