Association Between Metabolic Syndrome And Periodontitis:A Multi-Omics Analysis

To identify biomarkers and elucidate mechanisms underlying Metabolic syndrome (MetS)-associated periodontitis via integrative multi-omics analysis. Rat models of MetS, periodontitis, and dual-disease were established. Transcriptomic (RNA-seq) and metabolomic (LC-MS/MS) profiles of gingival tissues were analyzed to identify differentially expressed genes (DEGs) and metabolites, followed by pathway mapping. Successful establishment of rat models of MetS and periodontitis demonstrated that MetS exacerbates periodontal tissue destruction and alveolar bone resorption compared to periodontitis alone, as confirmed by histopathological analysis. Multi-omics integration identified distinct disease-associated signatures: periodontitis exhibited upregulated stress-response genes (e.g., Fosb, Fos) and inflammatory metabolites (e.g., LPC 24:4, β-nicotinamide mononucleotide), while the dual-disease group showed circadian rhythm regulators (Nr1d1), barrier dysfunction-related genes (LCE family), oxidative stress metabolites (ergothioneine), and immune-modulatory markers (neopterin, AICAR) when compared to controls or MetS alone. Functional crosstalk between dual-disease metabolites (cAMP, propionyl-L-carnitine) and the Sik1 gene implicated a Sik1-cAMP-AMPK feedback axis in pathogenesis, with cAMP, propionyl-L-carnitine, 8-isoprostaglandin F1β, and Sik1 proposed as biomarkers, highlighting phospholipase D signaling as a key mechanistic pathway linking metabolic dysregulation to periodontal inflammation. MetS exacerbates periodontitis progression. The identified biomarkers (cAMP, propionyl-L-carnitine, 8-isoprostaglandin F1β) and target gene (Sik1), along with the PLD signaling pathway, may serve as pivotal elements for understanding and managing MetS with periodontitis, highlighting their translational potential in future research.