Cross - Kingdom Dialogue of Microbial Messengers: Multi - Target Regulatory Mechanisms and Therapeutic Strategies of Gut Microbiota - Derived Extracellular Vesicles in Metabolic Diseases.

Gut microbiota-derived extracellular vesicles (GMEVs) serve as pivotal mediators of cross-communication between microorganisms and their hosts, playing a complex and central role in the onset and progression of metabolic diseases. This review systematically summarizes the biological characteristics, molecular composition, and regulatory mechanisms of GMEVs in metabolic disorders such as obesity, diabetes, and non-alcoholic fatty liver disease. GMEVs facilitate dialogue along the "gut-organ axis" by transporting active molecules such as lipopolysaccharides (LPS), flagellin, nucleic acids, and metabolic products, thereby mediating bidirectional regulation of host metabolic homeostasis. GMEVs derived from pathogenic bacteria promote metabolic inflammation and insulin resistance by compromising the intestinal barrier, activating inflammatory pathways, and inhibiting insulin signaling. Conversely, GMEVs originating from probiotics exert protective effects by enhancing tight junction functionality, modulating immune responses, and improving lipid metabolism. Notably, the dynamic fluctuations of GMEVs are closely linked to disease progression, and their microbiota-specific molecular characteristics offer novel biomarkers for the early diagnosis of metabolic diseases. Despite the challenges posed by standardization of isolation and elucidation of underlying mechanisms, the potential applications of GMEVs in the precise prevention and treatment of metabolic diseases are vast, providing a theoretical foundation for the development of novel microbiome-based intervention strategies. Future research should further elucidate the heterogeneity of GMEVs and their spatiotemporal dynamics in host interactions, facilitating the transition from fundamental research to clinical application.