Accumulating empirical evidence suggests that extracellular vesicles derived from gut microbiota (GM-EVs) function as independent biological entities that facilitate inter-kingdom communication between microorganisms and host cells. In addition to reflecting the composition of microbial communities, GM-EVs convey bioactive components including proteins, lipids, metabolites, and regulatory nucleic acids, which empower them to traverse biological barriers and modulate host immune, metabolic, and neuronal signaling cascades. In this narrative review, we systematically elucidate contemporary advancements in the cellular and molecular mechanisms by which GM-EVs influence host immunity and orchestrate gut-organ axes, with a specific emphasis on inflammatory, metabolic, and neurodegenerative pathologies. Particular focus is directed toward the gut-brain axis, underscoring emerging evidence that microbiota-derived EVs impact microglial activation, neuroinflammation, synaptic plasticity, and amyloid-β pathology, thereby playing a role in cognitive decline and the progression of Alzheimer's disease. We further examine the bifunctional roles of pathogenic versus probiotic-derived EVs in modulating host responses, underscoring their context-dependent influences on epithelial barrier integrity, immune polarization, and neural homeostasis. Ultimately, we investigate the translational applicability of gut microbiota-derived EVs as innovative biomarkers, postbiotic therapeutics, and drug-delivery systems, while confronting existing challenges pertaining to EV heterogeneity, standardization of isolation protocols, and mechanistic specificity. We additionally discuss emerging evidence that microbiota-derived EVs participate in maternal-fetal communication and prenatal immune programming by transmitting microbial and immunomodulatory signals that influence fetal immune maturation and developmental homeostasis. Collectively, this review delineates gut microbiota-derived extracellular vesicles as pivotal regulators of interkingdom signaling and as promising targets for precision interventions in the management of complex chronic diseases.
