The subgingival microbiome in periodontitis: from ecological dysbiosis and metabolic reprogramming to precision...

Periodontitis is a dysbiosis-driven chronic inflammatory disease characterized by complex interactions among the subgingival microbiome, microbial metabolism, and host immune responses. Accumulating evidence indicates that disease progression is not solely determined by the enrichment of specific periodontal pathogens but is critically associated with ecological disruption and functional reprogramming of the subgingival microbial community. During the transition from periodontal health to disease, microbial metabolism shifts from carbohydrate utilization toward proteolysis and amino acid fermentation, resulting in altered production of short-chain fatty acids, polyamines, volatile sulfur compounds, hydrogen sulfide, and nitric oxide. These metabolic alterations contribute to inflammasome activation, immune dysregulation, osteoclastogenesis, and progressive periodontal tissue destruction. Beyond local pathology, periodontal microorganisms and their metabolites can disseminate through the oral-systemic axis, thereby influencing the pathogenesis of multiple systemic disorders. Recent advances in multi-omics technologies have further revealed that metabolic reprogramming represents a critical mechanistic link connecting ecological dysbiosis with host inflammatory responses. Consequently, therapeutic strategies are evolving from conventional antimicrobial approaches toward precision microbiome-based interventions, including probiotics, postbiotics, bacteriophages, predatory bacteria, metabolic modulation, and oral microbiome transplantation. In this review, we integrate current evidence on microbial ecology, metabolism, and host interactions and propose the Ecological Dysbiosis-Metabolic Reprogramming-Host Crosstalk framework. This framework highlights metabolic reprogramming as the central bridge linking microbial dysbiosis to host inflammatory damage and provides a conceptual basis for the development of precision periodontal medicine.