Food-Derived microRNAs in Human Health: Bioavailability, Cross-Kingdom Regulation, Biomarker Potential and Applications in Functional Foods and Precision Nutrition

MicroRNAs (miRNAs) are small (19–24 nucleotide), non-coding RNAs that regulate post-transcriptional gene expression and play fundamental roles in maintaining cellular homeostasis and human health. Their disease-specific expression profiles have established them as promising biomarkers for the diagnosis, prognosis, and therapeutic monitoring of cancers, infectious diseases, cardiovascular disorders, neurological diseases, and metabolic conditions. More recently, miRNAs have been identified in diverse plant, animal, and microbial-derived foods, raising interest in their potential roles as bioactive dietary molecules capable of modulating human physiology following oral consumption. This review summarises current knowledge on food-derived miRNAs, their biological functions, cross-kingdom regulatory activities, and therapeutic potential. To achieve this, a literature search was undertaken across PubMed, Web of Science, and Scopus for articles published between January 2000 and May 2026. Keywords related to food-derived miRNAs, cross-kingdom regulation, stability mechanisms, and advanced biosensing platforms were utilised for article retrieval with a focus on peer-reviewed experimental and clinical studies. Beyond the biological roles of miRNAs, the review highlights the structural and biophysical determinants governing miRNA stability, including secondary structure, thermodynamic properties, Argonaute (AGO) interactions, extracellular vesicle encapsulation, and biomolecular assemblies that influence their persistence, transport, bioavailability, and regulatory activity. Recent advances in nanomaterial-enabled biosensors, electrochemical sensing, CRISPR-based diagnostics, super-resolution imaging, and microfluidic analytical platforms for miRNA detection and quantification are also discussed. Despite growing evidence supporting the biological relevance of dietary miRNAs, important challenges remain regarding their stability during food processing and gastrointestinal digestion, absorption, systemic transport, and definitive demonstration of bioactivity in humans. Collectively, this review highlights the potential of food-derived miRNAs in precision nutrition, biomarker discovery, functional food development, and RNA-based therapeutics while emphasizing the need for standardized analytical methodologies, mechanistic validation, and rigorous clinical investigation to facilitate future translational applications.