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

Cross-kingdom communication via non-coding RNAs is a recent discovery. Exogenous microRNAs (exog-miRNAs) mainly enter a host through diet. Generally considered unstable in the gastrointestinal (GI) tract, some exogenous RNAs may resist these harsh conditions, especially if transported in extracellular vesicles. They could then reach the intestines and more probably exert a regulatory effect. We provide an overview of recent discoveries concerning dietary miRNAs, possible ways of enhancing their resistance to technological processing and GI conditions, their transport in extracellular vesicles (animal- and plant-origin) and their possible biological effects on recipient cells after oral ingestion. We critically focus on what we believe are the most relevant data for future pharmacological development of dietary miRNAs as therapeutics. 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 for pharmacological development.