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Eating microRNAs: pharmacological opportunities for cross-kingdom regulation and implications in host gene and gut microbiota modulation

Journal

BRITISH JOURNAL OF PHARMACOLOGY
Volume 178, Issue 11, Pages 2218-2245

Publisher

WILEY
DOI: 10.1111/bph.15421

Keywords

cross‐ kingdom; cross species; diet; digestion; exosomes; food safety; miRNAs; ncRNA

Funding

  1. Marie Curie AMAROUT-II Europe Program [291803]
  2. Spanish Agencia Estatal de Investigacion
  3. European FEDER Funds [PID2019-109369RB-I00, AGL2018-78922-R, AGL2017-90623-REDT]
  4. Fundacion Ramon Areces [CIVP18A3888]

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Cross-kingdom communication through non-coding RNAs, particularly exogenous miRNAs ingested through diet, has risen as a novel discovery. These miRNAs, considered unstable in the gastrointestinal tract, may resist conditions and exert regulatory effects after being transported in extracellular vesicles. Despite challenges, extracellular miRNAs show promise as potential therapeutic agents for future pharmacological development.
Cross-kingdom communication via non-coding RNAs is a recent discovery. Exogenous microRNAs (exog-miRNAs) mainly enter the host via the diet. Generally considered unstable in the gastrointestinal tract, some exogenous RNAs may resist these conditions, especially if transported in extracellular vesicles. They could then reach the intestines and more probably exert a regulatory effect. We give an overview of recent discoveries concerning dietary miRNAs, possible ways of enhancing their resistance to food processing and gut conditions, their transport in extracellular vesicles (animal- and plant-origin) and possible biological effects on recipient cells after ingestion. We critically focus on what we believe are the most relevant data for future pharmacological development of dietary miRNAs as therapeutic agents. Finally, we discuss the miRNA-mediated cross-kingdom regulation between diet, host and the gut microbiota. We conclude that, despite many obstacles and challenges, extracellular miRNAs are serious candidates to be targeted pharmacologically for development of new therapeutic agents.

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