Gut Microbiota-Derived Extracellular Vesicles in Cancer: Friends or Foes?

The gut microbiota has emerged as a key regulator of cancer biology through its dynamic interaction with host immunity, metabolism, and cellular signaling. Recent evidence highlights that gut microbiota-derived extracellular vesicles (GMEVs), nanosized bi-layered particles secreted by gut bacteria, play a pivotal role in mediating microbiota-host communications. Unlike whole bacteria, GMEVs can cross epithelial and vascular barriers, circulate systemically, and deliver bioactive cargo including proteins, nucleic acid, and metabolites to distant organs exerting profound effects on tumor development and therapy. This review provides an up-to-date overview of the dual role of GMEVs in cancer. A comprehensive literature search was conducted across PubMed, Scopus, Web of Science, and Google Scholar without time restrictions using standardized keywords related to gut microbiota, extracellular vesicles, and cancer. Studies were included based on relevance to GMEVs biogenesis, mechanisms of host interaction, and functional roles in cancer hallmarks. Within the Yin-Yang conceptual framework, GMEVs associated with pathogenic or dysbiotic microbial states may promote tumorigenesis as demonstrated by vesicles derived from Fusobacterium nucleatum, Escherichia coli, Bacteroides fragilis, and Enterococcus faecalis foster tumorigenesis by inducing inflammation, sustaining proliferative signaling, promoting epithelial-mesenchymal transition, reprogramming cellular metabolism, and enabling immune evasion. Conversely, GMEVs derived from beneficial or commensal bacteria may exhibit therapeutic potential, particularly those from Akkermansia muciniphila, Lactobacillus plantarum, and attenuated Escherichia coli, which have demonstrated therapeutic effects by restoring intestinal homeostasis, suppressing tumor-associated inflammation, enhancing antitumor efficacy, and serving as natural delivery systems for targeted therapy and cancer vaccines. Understanding the complex Yin-Yang paradigm of GMEVs offers exciting opportunities in oncology. Future research should focus on mechanistic validation, biosafety profiling, and clinical translation of GMEV based-therapeutics.