Matsagani · International journal of molecular sciences 2026 · narrative review · n=?

An Apple a Day? The Hypothesis of Cross-Kingdom Gene Regulation by Plant miRNAs in Mammals and Its Controversies.

Cited 2 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Narrative review synthesizing existing mechanistic and observational literature without new human data or systematic review methodology.

PubMed 42196200 · doi:10.3390/ijms27104220 · record verified 2026-08-29

What was done

This narrative review synthesized the published literature regarding the hypothesis of cross-kingdom gene regulation by dietary plant-derived microRNAs (pmiRNAs) in mammals. The authors reviewed evidence evaluating whether pmiRNAs survive cooking and digestion, enter systemic circulation via extracellular vesicles, and reach tissues to exert gene-regulatory effects, while addressing methodological challenges and contrasting positive reports with non-replication studies.

What was found

The abstract reports no numerical findings. It states that while several studies suggest plant miRNAs survive processing and digestion to enter circulation and mediate cross-kingdom gene expression, multiple subsequent studies have failed to reproduce or confirm these results, leaving the biological reality of the mechanism in question.

Why it matters

Understanding whether dietary plant miRNAs can functionally alter mammalian gene expression is foundational for nutritional genomics and therapeutic RNA delivery. The review highlights analytical pitfalls and aims to establish best practices for future investigations.

Limits

As a narrative review, it presents no original experimental data, quantitative synthesis, or systematic search protocol. The broader field is limited by substantial reproducibility issues, low physiological concentrations, and analytical artifacts in sequencing and detection assays.

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