Metagenome-based virome analysis identifies the oral viral signatures for periodontitis

Background: Periodontitis (PD) is a chronic infectious disease driven by bacterial biofilms, yet the oral virome's role in pathogenesis remains poorly understood. Objective: This cross-cohort meta-analysis aims to define PD-associated viral signatures, characterize predicted virus-host interactions, and evaluate the diagnostic potential of viral biomarkers. Methods: We integrated 89 saliva (44 PD, 45 healthy) and 86 subgingival plaque (48 PD, 38 healthy) metagenomes from six public cohorts for a unified virome analysis. Results: -targeting phages were decreased. PD-associated vOTUs harbored diverse bacterial defense and anti-defense systems, with those enriched in PD overrepresenting lysozyme and replication-associated genes. Diagnostic models based on key viral markers achieved robust performance, with AUCs of 0.95 (saliva) and 0.92 (subgingival plaque) for classifying PD. Conclusion: This study delineates a distinct oral virome profile in PD, highlights predicted virus-host interactions, and underscores the potential of viral biomarkers for PD diagnosis,providing a basis for future investigations into viral ecology and phage-based interventions.