Oral–systemic metabolic crosstalk linking periodontal inflammation to energy homeostasis dysregulation

Introduction: Periodontal inflammation is increasingly linked to systemic metabolic dysfunction, although its mechanism of involvement in energy balance is unclear. Microbial dysbiosis and chronic periodontitis cause inflammation and affect insulin signalling and lipid metabolism. Methods: This study introduces the PerioMet-HOMEOSTASIS framework to examine oral–systemic metabolic crosstalk using integrated physiological and biochemical methods, including periodontal assessment, cytokine profiling, microbial sequencing, and metabolomics. Results: XAI analysis reveals that severe periodontal inflammation leads to a 50–60% rise in pro-inflammatory cytokines and a 30–35% decrease in insulin sensitivity, with inflammation-driven pathways as key contributors. Conclusion: The proposed framework provides a mechanistically interpretable understanding of oral–systemic metabolic interactions. The integration of Explainable AI enhances transparency and supports early prediction and targeted intervention for metabolic disorders, aligning with the principles of integrative metabolism research.