Abstract
BACKGROUND: Dyslipidemia has been implicated as a risk factor for periodontitis; however, the underlying mechanisms remain poorly understood. This study aims to investigate the correlation between blood lipid levels and periodontitis and to explore the cellular and molecular mechanisms linking dyslipidemia to periodontal disease. METHODS: Participants with complete data on serum lipid levels and periodontal examinations were selected from the 2009-2014 National Health and Nutrition Examination Survey (NHANES). Subgroup and logistic regression analyses were performed to assess the associations between periodontal status and lipid profiles, including triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and remnant cholesterol (RC). Single-cell Ribonucleic Acid (RNA) sequencing (scRNA-seq) statistical analysis, cellular metabolic pathway analysis, and CellChat were employed to examine cellular variations and intercellular communication in periodontal tissues with and without periodontitis. RESULTS: A total of 5,342 participants were included in the analysis. Subgroup analyses revealed significant positive associations between elevated levels of TG, TC, and LDL-C and the prevalence of severe periodontitis. Participants in the high TC group had a 55% higher risk of severe periodontitis compared to those in the normal TC group (OR = 1.55, 95% CI: 1.17-2.05). Similarly, the risk of severe periodontitis increased by 50% in the high LDL-C group (OR = 1.50, 95% CI: 1.09-2.06) and by 35% in the high TG group (OR = 1.35, 95% CI: 1.02-1.79). scRNA-seq analysis revealed enhanced lipid metabolism in immune cells, particularly mast cells, within the periodontitis group. These mast cells were found to modulate fibroblast activity through inflammatory signaling pathways such as Interleukin 7 (IL7), Interleukin 15 (IL15). CONCLUSIONS: Elevated blood lipid levels are associated with an increased risk of severe periodontitis, potentially mediated by enhanced lipid metabolism in immune cells, particularly mast cells, and their interactions with fibroblasts via inflammatory signaling pathway. These findings suggest the importance of monitoring lipid levels in periodontitis patients with dyslipidemia and highlight potential therapeutic targets for managing periodontal disease in this population.