Differential Associations of Human Herpesviruses With Oral Bacteria and Periodontitis Severity: A Cross-Sectional...

The polymicrobial synergy and dysbiosis model is increasingly recognized as a key pathogenic factor in periodontitis. Human herpesviruses (HHVs), including EBV, HCMV, and HSV-1, have been linked to periodontitis development. However, current research lacks sufficient evidence to clarify the correlation between HHVs, periodontitis progression, and periodontal microbiota. This study aimed to investigate the association between HHVs in gingival crevicular fluid (GCF) and periodontitis severity, as well as the correlation patterns between viruses and periodontal microbiota.

A total of 339 subjects (64 healthy controls, 275 periodontitis patients) were stratified according to the 2018 periodontitis classification criteria. Viral loads were quantified by quantitative real-time PCR (qPCR), and microbial communities were analysed via high-throughput 16S rRNA sequencing.

HCMV and EBV loads were significantly positively correlated with clinical parameters including probing depth (PD), clinical attachment loss (CAL), and bleeding on probing (BOP) (all P < .001), and their infection status was closely associated with periodontitis staging. HSV-1 showed no significant association with any periodontal indicators (P > .05). In the EBV/HCMV coinfection group, 92.9% of patients were classified as stage II-IV periodontitis, suggesting potential combined viral associations with disease severity. Microbiome analysis revealed significantly higher microbial diversity in the HCMV-H compared to the HCMV-L. HCMV load was positively correlated with known pathogens such as Porphyromonas gingivalis and Tannerella forsythia, as well as novel associated bacteria (eg, Schwartzia succinivorans, Peptostreptococcus stomatis). Functional prediction showed significant enrichment of microbial metabolic pathways in HCMV-H patients, including Helicobacter pylori infection and isoquinoline alkaloid biosynthesis.

HCMV is strongly associated with periodontitis severity and bacterial dysbiosis, while EBV acts as an independent risk factor correlated with periodontitis severity. In contrast, HSV-1 shows no significant association with periodontitis severity. This study provides new evidence for the polymicrobial pathogenesis of periodontitis and highlights virus-bacteria associations as potential therapeutic targets, although further longitudinal studies are needed to establish causality.