Mechanistic Study Of Periodontal Disease And Metabolic Syndrome

To address confounding biases in observational studies, this study integrated Mendelian randomization (MR) and multi-omics bioinformatics analysis to systematically identify periodontal disease–metabolic syndrome (PD-MetS) associated genes and validate their functions in animal models. MR analysis using GWAS data assessed the genetic causality between PD and MetS, with IVW as the primary statistical model. Multi-omics integration identified differentially expressed genes from GEO datasets, and eQTL data combined with MetS GWAS revealed core PD-MetS comorbid genes. This study was approved by the Ethics Committee [2024-AE340].A 20-week in vivo study in 40 male SD rats, divided into normal and high-fat, high-fructose diet groups, induced MetS over 12 weeks, with PD modeled by 8-week periodontal ligation. Physiological, biochemical, and histological analyses assessed insulin resistance and lipid metabolism. qRT-PCR and Western blot confirmed gene expression in gingival and liver tissues. MR analysis using GWAS data identified a significant unidirectional causal relationship between PD and MetS, suggesting that PD may be an independent risk factor for MetS. Multi-omics integration revealed CYTIP as a key mediator gene positively correlated with MetS, and animal experiments demonstrated that PD exacerbates hepatic lipid metabolism disorders. Furthermore, PD and MetS synergistically aggravated each other’s pathology, with CYTIP and TNF-α showing synchronized upregulation, implicating inflammatory pathways in their comorbid mechanism. These findings provide multidimensional evidence supporting a causal link between PD and MetS, highlighting CYTIP as a potential molecular bridge in their comorbid pathology.