Evidence map›Paper›PMID 34716465›Full record

ArticleEuropean journal of nutrition2022

Dietary bovine milk miRNAs transported in extracellular vesicles are partially stable during GI digestion, are bioavailable and reach target tissues but need a minimum dose to impact on gene expression.

María-Carmen López de Las Hazas, Lorena Del Pozo-Acebo, Maria S Hansen, Judit Gil-Zamorano, Diana C Mantilla-Escalante, Diego Gómez-Coronado, Francisco Marín, Almudena Garcia-Ruiz, Jan T Rasmussen, Alberto Dávalos

Abstract read
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In one paragraph

Article in European journal of nutrition, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed
5.4field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

54 citing papers in PubMed, 93 citations in OpenAlex.

  1. Article
  2. Investigating Dietary microRNA Stability and Function Using a Transgenic Milk Model With Unique microRNA Sequences.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
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  17. Milk-Derived Extracellular Vesicles and microRNAs: Potential Modulators of Intestinal Homeostasis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 2 countries.

María-Carmen López de Las Hazas *Laboratory of Epigenetics of Lipid Metabolism, IMDEA Food Institute, CEI UAM+CSIC, Ctra. De Cantoblanco 8, 28049, Madrid, Spain.
Lorena Del Pozo-AceboLaboratory of Epigenetics of Lipid Metabolism, IMDEA Food Institute, CEI UAM+CSIC, Ctra. De Cantoblanco 8, 28049, Madrid, Spain.
Maria S HansenDepartment of Molecular Biology and Genetics, Aarhus University, 8000, Aarhus, Denmark.
Judit Gil-ZamoranoLaboratory of Epigenetics of Lipid Metabolism, IMDEA Food Institute, CEI UAM+CSIC, Ctra. De Cantoblanco 8, 28049, Madrid, Spain.
Diana C Mantilla-EscalanteLaboratory of Epigenetics of Lipid Metabolism, IMDEA Food Institute, CEI UAM+CSIC, Ctra. De Cantoblanco 8, 28049, Madrid, Spain.
Diego Gómez-CoronadoDepartment of Biochemistry-Research, Hospital Universitario Ramón y Cajal, IRYCIS, 28034, Madrid, Spain.
Francisco MarínDepartment of Applied Chemistry-Physics, Faculty of Science, University Autónoma of Madrid, 28049, Madrid, Spain.
Almudena Garcia-RuizLaboratory of Epigenetics of Lipid Metabolism, IMDEA Food Institute, CEI UAM+CSIC, Ctra. De Cantoblanco 8, 28049, Madrid, Spain.
Jan T RasmussenDepartment of Molecular Biology and Genetics, Aarhus University, 8000, Aarhus, Denmark.
Alberto DávalosLaboratory of Epigenetics of Lipid Metabolism, IMDEA Food Institute, CEI UAM+CSIC, Ctra. De Cantoblanco 8, 28049, Madrid, Spain. alberto.davalos@imdea.org.ORCID http://orcid.org/0000-0001-5709-6443
Madrid Institute for Advanced Studies · ESAarhus University · DKInstituto de Salud Carlos III · ESUniversidad Autónoma de Madrid · ES

Funding

Agencia Estatal de Investigación (ES) and European FEDER Funds PID2019-109369RB-I00Agencia Estatal de Investigación (ES) and European FEDER Funds RTI2018-093873-A-I00Agencia Estatal de Investigación (ES) and European FEDER Funds RTI2018-098113-B-I00Milk Levy Foundation PHLIP Project
6 · The paper itself

Abstract

purposeExtracellular RNAs are unstable and rapidly degraded unless protected. Bovine-milk extracellular vesicles (EVs) confer protection to dietary miRNAs, although it remains unclear whether this importantly improves their chances of reaching host target cells to exert biological effects.

methodsCaco-2, HT-29, Hep-G2 and FHs-74 cell lines were exposed to natural/labelled milk EVs to evaluate cellular uptake. Five frequently reported human milk miRNAs (miR-146b-5p, miR-148a-3p, miR-30a-5p, miR-26a-5p, and miR-22-3p) were loaded into EVs. The intracellular concentration of each miRNA in cells was determined. In addition, an animal study giving an oral dose of loaded EVs in C57BL6/ mice were performed. Gene expression regulation was assessed by microarray analysis.

resultsDigestive stability analysis showed high overall degradation of exogenous miRNAs, although EV-protected miRNAs better resisted gastrointestinal digestion compared to free miRNAs (tenfold higher levels). Importantly, orally delivered EV-loaded miRNAs reached host organs, including brain, in mice. However, no biological effect has been identified.

conclusionMilk EVs protect miRNAs from degradation and facilitate cellular uptake. miRNA concentration in EVs from bovine milk might be insufficient to produce gene modulation. Nevertheless, sizable amounts of exogenous miRNAs may be loaded into EVs, and orally delivered EV-loaded miRNAs can reach tissues in vivo, increasing the possibility of exerting biological effects. Further investigation is justified as this could have an impact in the field of nutrition and health (i.e., infant formulas elaboration).

Indexed as

Extracellular VesiclesMicroRNAsAnimalsCaco-2 CellsDigestionGene ExpressionHumansMiceMilk, HumanMicroRNAsExosomesExtracellular vesiclesIn vitro digestionMilk miRNAsTranscriptomeTransfection

Identifiers

PMID34716465
OpenAlexW3208336880

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.