Human microbiome alterations in Epstein-Barr Virus infection: a systematic review

Epstein-Barr virus (EBV) is associated with several malignancies and immune-mediated conditions, but its relationship with human microbial communities remains incompletely understood. We systematically searched PubMed, Embase, and Scopus for human studies evaluating EBV-associated alterations in the microbiome. Because of substantial clinical and methodological heterogeneity, findings were synthesized narratively, and study quality was assessed using the ROBINS-I tool. Nine observational studies published between 2017 and 2025 were included, covering the oral cavity, nasopharynx, gut, gastric tissue, and subgingival plaque. EBV positivity or EBV-related clinical status was associated with niche-specific microbial shifts, including altered gut bacterial profiles, distinct microbial patterns in EBV-associated gastric cancer tissue, and enrichment of oral-associated pathobionts in nasopharyngeal carcinoma compartments. Alpha- and beta-diversity findings were inconsistent across studies. Overall, the evidence suggests context-dependent alterations in the microbiome in EBV-positive or EBV-related disease settings. However, these findings should be interpreted as EBV-associated rather than EBV-specific, particularly when EBV status overlaps with malignancy. The small observational evidence base, heterogeneous EBV-status definitions, methodological variability, and residual confounding limit causal inference. Larger longitudinal and standardized multi-omic studies are needed to clarify directionality, mechanisms, and clinical relevance.