Decoding metabolic diseases through bacterial extracellular vesicles: mechanisms, diagnostics, and therapeutics.

Metabolic diseases represent a class of chronic conditions characterized by disturbances in energy and material metabolism. These diseases primarily include obesity, metabolic dysfunction-associated steatotic liver disease, atherosclerosis, type 2 diabetes, osteoporosis, and polycystic ovary syndrome. A core pathological feature underlying their development is the mutual reinforcement between chronic low-grade inflammation and metabolic imbalance. The gut microbiota has been highlighted by recent research as a key regulator of host metabolism, while bacterial extracellular vesicles (BEVs) are emerging as critical mediators. BEVs transport bioactive molecules (proteins, lipids, nucleic acids) to facilitate microbiota-host crosstalk without direct contact. Pathogen-derived BEVs often exacerbate metabolic dysfunction via inflammation, while commensal/probiotic BEVs protect against disorders by enhancing intestinal barrier function and regulating immunity. Furthermore, owing to their high stability, easy penetration of biological barriers, and capacity to carry abundant cellular information, BEVs demonstrate broad application prospects as non-invasive diagnostic biomarkers for metabolic diseases and as natural or engineered targeted drug delivery vehicles. This review outlines the mechanisms and progress in the application of gut BEVs in metabolic diseases. It aims to deepen our understanding of host-microbiota interaction networks and support the development of novel intervention strategies for metabolic diseases.