Work

Dietary exogenous microRNAs in the gut: biological effects, mechanistic evidence, and controversies

Year: 2026

Type: review

Abstract: Dietary exogenous microRNAs (miRNAs) have emerged as potential mediators of interorganismal communication, with growing interest in their ability to influence gastrointestinal physiology and the gut microbiota. These molecules encompass plant-derived miRNAs implicated in cross-kingdom regulation, animal-derived dietary miRNAs involved in cross-species communication, and maternal milk miRNAs that may participate in mother-to-offspring molecular crosstalk. A proportion of dietary miRNAs are associated with extracellular vesicles or other protective complexes, which may enhance their stability during food processing and gastrointestinal transit and facilitate interactions with intestinal epithelial cells, immune cells, and microbial communities. This review critically evaluates recent computational, detection-based, in vitro , in vivo , and human observational evidence concerning the gastrointestinal stability, uptake, target engagement, and biological activity of dietary exogenous miRNAs. Experimental studies have reported effects on inflammatory signaling, epithelial barrier integrity, macrophage polarization, intestinal development, tumor-associated pathways, and gut microbial composition and gene expression. However, the strength of this evidence varies considerably. In particular, detection of dietary miRNAs in food, extracellular vesicles, feces, or recipient tissues does not by itself establish functional target regulation, while studies using purified vesicles, synthetic miRNA mimics, or engineered delivery systems may involve exposures that differ substantially from normal dietary intake. Moreover, biological effects observed following whole-vesicle administration cannot always be attributed specifically to their miRNA cargo. Collectively, current evidence provides stronger support for the biological plausibility of local gastrointestinal effects than for widespread systemic regulation after dietary exposure. Further studies using physiologically relevant doses, rigorous miRNA-specific loss-of-function approaches, direct target validation, standardized analytical methods, and controlled human interventions will be essential to establish the functional significance and translational potential of dietary exogenous miRNAs.

Source: Frontiers in Nutrition

DOI: 10.3389/fnut.2026.1974997