Reassessing Biofilm Dysbiosis as the Primary Etiological Driver in Chronic Periodontitis: Beyond the Keystone Pathogen Hypothesis

Abstract

The keystone pathogen hypothesis has dominated periodontal etiopathogenesis discourse for over a decade, positioning Porphyromonas gingivalis as the principal orchestrator of polymicrobial synergy and dysbiosis. However, accumulating metagenomic and transcriptomic evidence challenges the sufficiency of this model in explaining the full spectrum of chronic periodontitis progression. This study performed a systematic meta-analysis of 47 clinical cohort datasets (n = 6,312 subjects), integrating 16S rRNA amplicon sequencing, host immunogenomic profiling, and subgingival metabolomics. Findings demonstrate that polymicrobial community restructuring—driven by shifts in Treponema denticola, Tannerella forsythia, and Filifactor alocis abundance ratios—predicts clinical attachment loss with greater fidelity than P. gingivalis load alone. These results necessitate a fundamental re-evaluation of treatment paradigms targeting single-species virulence and advocate for community-level antimicrobial intervention strategies.