From Microbiota to Cancer: Role of Extracellular Vesicles in Gut-Lung Axis.

Lung cancer (LC) remains the leading cause of cancer-related mortality worldwide, and resistance to therapy continues to pose a major clinical challenge. Increasing evidence highlights the relevance of the gut-lung axis in immune response modulation, tumor progression, and treatment outcomes. Within this inter-organ network, bacterial extracellular vesicles (bEVs), nanosized particles containing proteins, nucleic acids, and metabolites, serve as important mediators of host-microbiota communication, influencing immune regulation, metabolic pathways, and tumor biology. This review explores EV-mediated mechanisms involved in LC pathogenesis, including immune modulation, epigenetic regulation, and microbial metabolite signaling. The mechanistic influence of environmental and dietary factors on bEV composition and function is further explored, and emerging translational applications, ranging from diagnostic biomarker development to drug delivery strategies and modulation of immunotherapy responses, are discussed. Moreover, ongoing clinical trials testing microbiota-based strategies in non-small cell lung cancer (NSCLC) are summarized, offering potential new perspectives for personalized cancer management.