Extracellular vesicle miRNAs as key mediators in diet-gut microbiome-host interplay

Background: Gut microbiome, the modifiable "second genome" of human body, is increasingly recognized as a critical determinant of human health and disease. Host genetic and dietary factors are key players in shaping microbial composition. Particularly striking has been the diet-derived exogenous and host-derived endogenous miRNAs packaged in extracellular vesicle (EV, an emerging messenger of intercellular communication), which are newly identified as specific modulators of gut microbiota. Scope and approach: Developing microbiota-based strategies for precision nutrition, disease management and personalized treatment necessitates a robust understanding of the intricate linkages between diet, gut microbiome and host. In this Review, we integrate emerging evidence on the extrinsic and intrinsic EVs or EV miRNAs closely tied to gut microbes. Key findings and conclusions: Edible foods-derived EV miRNAs, under the protection of lipid bilayers, are exempt from decomposition by the digestive system and then are selectively taken up by certain gut microbes to specifically affect their growth. Excavating specific miRNAs in foodstuffs with potential prebiotic effects are prospective to facilitate the application of "probiotic miRNAs" as novel natural materials in designing microbiotadirected foods. Moreover, studies on host-gut microbiota crosstalk shed light on the endogenous EV miRNAsmediated regulatory mechanism by which the host manipulates gut microbiome, highlighting the potential of host cells-secreted EV miRNAs as novel diagnostic/prognostic biomarkers and therapeutic targets for gut microbiota-related diseases. Intriguingly, as a rising field in biomedicine, gut microorganisms-derived EVs, which can deliver the bioactive microbial components not only to local but also to distal tissues, in turn affect the host physiology on multiple facets. Continued advances on candidate miRNAs specifically targeting microbiota may elicit tangible impacts on human health.