Bacterial and gut microbiota-derived extracellular vesicles as emerging sources of cancer biomarkers: molecular mechanisms, diagnostic approaches, and therapeutic applications.

Extracellular vesicles (EVs) originating from bacteria and gut microbiota have recently been recognized as pivotal agents in the communication between host and microbes, exhibiting considerable promise as innovative biomarkers and therapeutic instruments in the realm of oncology. These nanoscale vesicles encapsulate a heterogeneous array of molecular constituents, including metabolites, proteins, nucleic acids, and toxins, which possess the capacity to influence tumor proliferation, apoptosis, immune responses, and metastasis. Recent investigations underscore their bifunctional nature: specific bacterial EVs can facilitate oncogenesis by altering signaling cascades such as BRCA1/EXO1/TP53BP1 or TGF-β1/Smad, while others may suppress tumor growth through the induction of oxidative stress, mitophagy, or the activation of antitumor immunity via STING or cGAS pathways. The metabolomic and molecular characterizations of bacterial and fecal EVs afford a distinctive, non-invasive perspective into tumor biology and the interactions between host and microbiome. Sophisticated diagnostic methodologies, encompassing targeted metabolomics, high-throughput sequencing, and flow cytometry-based characterization of EVs, have enabled the discovery of EV-derived cancer biomarkers with exceptional specificity and sensitivity. Moreover, engineered EVs that transport therapeutic agents, including prodrugs, microRNAs, or photosensitizers, exhibit significant anticancer efficacy in preclinical experimental models. This review consolidates contemporary understanding regarding the molecular mechanisms, diagnostic capabilities, and therapeutic implications of bacterial and gut microbiota-derived EVs in the context of cancer.