The microbiome-EBV axis in carcinogenesis bridges commensal influence and viral oncogenesis

This review synthesizes current evidence on the emerging role of the host microbiome in Epstein-Barr virus (EBV)-associated tumorigenesis. Moving beyond the traditional virus-host paradigm, we propose the "microbiome-EBV axis" as a conceptual framework for understanding interactions among microbial communities, microbial metabolites, EBV-infected cells, and the host tissue-immune environment during carcinogenesis. We summarize four interrelated mechanisms: microbial regulation of EBV latency and lytic reactivation, microbiome-associated remodeling of the immune microenvironment, microbial contribution to genomic and epigenetic instability, and the potential translational use of microbial signatures or microbiome-targeted interventions. Importantly, we distinguish mechanistic evidence derived from in vitro and animal studies, observational associations from clinical cohorts, and findings supported by clinical validation. Overall, this framework refines our understanding of EBV-associated cancers while highlighting microbiome-derived biomarkers and therapeutic strategies as promising, but still incompletely validated, areas for future investigation.