Gut microbiota-derived extracellular vesicles: bridging microbial-host crosstalk in metabolic disorders.

Gut microbiota-derived extracellular vesicles have emerged as crucial mediators in microbe-host communication, not only facilitating intracellular communication, quorum sensing, and horizontal gene transfer among bacteria but also playing a central role in cross-kingdom dialogue. In recent years, bacterial extracellular vesicles (BEVs) have attracted widespread attention due to their ability to carry a diverse array of bioactive molecules-such as proteins, lipids, and nucleic acids-and deliver them to host cells, thereby precisely regulating host metabolic and immune homeostasis. This review systematically elaborates the entire biological process of BEVs, from their biogenesis to functional interactions with host cells, with a specific emphasis on revealing their roles in the pathogenesis of various metabolic diseases-including obesity, type 2 diabetes (T2DM), metabolic dysfunction-associated steatotic liver disease (MASLD), atherosclerosis, and hypertension-at both molecular and cellular levels. Furthermore, leveraging their inherent stability, biocompatibility, and targeting capabilities, we discuss the translational potential and challenges of BEVs in the diagnosis and treatment of metabolic disorders. Beyond summarizing the latest research advances on BEVs in metabolic disorders, this review provides a critical analysis of current mechanistic insights and clinical translation pathways, aiming to establish a theoretical framework for developing novel microbiome-based metabolic interventions. Deciphering the BEV-mediated microbiota-host interaction network holds promise for pioneering new strategies for the precision prevention and treatment of metabolic disease.