Gut-derived bacterial extracellular vesicles: the microbial dark matter contributing to host inflammation and cardiometabolic disease.

Cardiometabolic diseases (CMDs) represent a growing global health burden, with chronic inflammation and gut microbiota dysbiosis emerging as central contributors to their pathogenesis. Among the diverse microbial products influencing host physiology, bacterial extracellular vesicles (BEVs) have gained attention as potent mediators of interkingdom communication. These nanoscale vesicles, secreted by both gram-positive and gram-negative bacteria, carry a complex cargo of proteins, lipids, nucleic acids, and pathogen-associated molecular patterns (PAMPs) that interact with host pattern recognition receptors (PRRs) to modulate immune and metabolic responses. BEVs can traverse intestinal barriers, disseminate systemically, and accumulate in cardiometabolic tissues, where they influence inflammation, insulin sensitivity, and organ function. This review synthesizes current evidence linking BEVs to CMDs, explores mechanisms of BEV-host crosstalk, and highlights their potential as diagnostic biomarkers and therapeutic vectors. We also discuss emerging technologies for BEV characterization and propose future research directions to better understand their role in CMD pathophysiology.