{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T12:46:33Z","timestamp":1791809193423,"version":"4.3.4"},"reference-count":478,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,6,7]],"date-time":"2021-06-07T00:00:00Z","timestamp":1623024000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>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-\u03baB (NF-\u03baB) 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\u2014which is important for the up-regulation of developmental genes including insulin, insulin-like growth factor-1, \u03b1-synuclein and forkhead box P3\u2014and 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\u2019s molecular biology allow the conclusion that infants are both \u201cbreast-fed\u201d and \u201cbreast-programmed\u201d. In this regard, MEX miRNA-deficient artificial formula is not an adequate substitute for breastfeeding, the birthright of all mammals.<\/jats:p>","DOI":"10.3390\/biom11060851","type":"journal-article","created":{"date-parts":[[2021,6,7]],"date-time":"2021-06-07T13:25:43Z","timestamp":1623072343000},"page":"851","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":178,"title":["Exosome-Derived MicroRNAs of Human Milk and Their Effects on Infant Health and Development"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4501-1809","authenticated-orcid":false,"given":"Bodo C.","family":"Melnik","sequence":"first","affiliation":[{"name":"Department of Dermatology, Environmental Medicine and Health Theory, University of Osnabr\u00fcck, D-49076 Osnabr\u00fcck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Stremmel","sequence":"additional","affiliation":[{"name":"Private Praxis for Internal Medicine, Beethovenstra\u00dfe 2, D-76530 Baden-Baden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3888-0931","authenticated-orcid":false,"given":"Ralf","family":"Weiskirchen","sequence":"additional","affiliation":[{"name":"Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry (IFMPEGKC), RWTH University Hospital Aachen, D-52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swen Malte","family":"John","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Environmental Medicine and Health Theory, University of Osnabr\u00fcck, D-49076 Osnabr\u00fcck, Germany"},{"name":"Institute for Interdisciplinary Dermatological Prevention and Rehabilitation (iDerm), University of Osnabr\u00fcck, D-49076 Osnabr\u00fcck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1325-1007","authenticated-orcid":false,"given":"Gerd","family":"Schmitz","sequence":"additional","affiliation":[{"name":"Institute for Clinical Chemistry and Laboratory Medicine, University Hospital of Regensburg, University of Regensburg, D-93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/nri3112","article-title":"The impact of perinatal immune development on mucosal homeostasis and chronic inflammation","volume":"12","author":"Renz","year":"2011","journal-title":"Nat. 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