Deciphering the immunomodulatory cross-talk: Bacterial extracellular vesicles in gut homeostasis

Within mammalian gastrointestinal ecosystems, trillions of microorganisms generate sophisticated ecological networks through bacterial extracellular vesicles (bEVs). Emerging evidence positions these bEVs as pivotal mediators in gut homeostasis maintenance and host-microbiota crosstalk, capable of transporting bioactive cargo including virulence determinants, genetic transfer components, and host-derived defense molecules. This molecular payload enables bEVs to exert multifaceted immunomodulatory effects through: 1) Immune cell activation and differentiation. 2) Microbial community regulation. 3) Epithelial barrier reinforcement. This review systematically examines current understanding of bEV biology: First, we characterize the structural complexity and compositional diversity of bEVs across bacterial species. Second, we elucidate the molecular machinery governing bEV biogenesis and secretion pathways. Third, we analyze mechanisms underlying bEV-immune interactions through receptor-mediated signaling and cargo delivery processes. By integrating recent advances in bEV immunobiology with mechanistic insights into host-pathobiont communication networks, our framework not only clarifies current knowledge gaps but also proposes standardized methodologies for future investigations.