口腔疾病与动脉粥样硬化可能与重叠的代谢途径相关。
Oral Disease and Atherosclerosis May Be Associated with Overlapping Metabolic Pathways.
作者信息
Bezamat M, Saeed A, McKennan C, Duan J, Zhou R, Baxter D J, Liu L, Las Fuentes L de, Foxman B, Shaffer J R, McNeil D W, Marazita M L, Reis S E
机构信息
Department of Oral and Craniofacial Sciences, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Heart and Vascular Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
出版信息
JDR Clin Trans Res. 2025 Jul;10(3):315-323. doi: 10.1177/23800844241280383. Epub 2024 Oct 9.
OBJECTIVES
Dental caries and periodontitis are among the most prevalent chronic diseases worldwide and have been associated with atherosclerotic cardiovascular diseases (ASCVD). This study aimed to determine (1) the independent associations between subclinical ASCVD markers (carotid intima media thickness [CIMT] and coronary artery calcification [CAC]) and quantitative indices of oral disease including the decayed, missing, and filled teeth (DMFT) index, gingivitis parameters, periodontal status, and number of teeth lost and (2) the extent to which metabolites altered in individuals with oral disease overlapped with those altered in individuals with ASCVD.
METHODS
We used data from 552 participants recruited through the Dental Strategies Concentrating on Risk Evaluation project. Oral examinations were conducted, and CIMT and CAC were measured. Multiple linear regression models were constructed with CIMT and CAC as dependent variables in the epidemiologic analysis. In the metabolomic analysis, logistic or linear regression was used to test 1,228 metabolites for association with each phenotype adjusted for age, sex, race, blood pressure, smoking, diabetes, cholesterol, high-sensitivity C-reactive protein, and interleukin-6.
RESULTS
None of the oral disease markers were significant predictors of ASCVD markers in the fully adjusted models. However, critical lipid and lipid-signaling pathway metabolites were significantly associated with gingivitis, periodontitis, and DMFT: the lysophospholipid pathway (odds ratio [OR] = 2.29, false discovery rate [FDR]-adjusted = 0.038) and arachidonate with gingivitis (OR = 2.35, FDR-adjusted = 0.015), the sphingolipid metabolism pathway with periodontitis (OR = 2.09, FDR-adjusted = 0.029), and borderline associations between plasmalogen and lysophospholipid pathways and DMFT (P = 0.055). Further, the same metabolite from the sphingolipid metabolism pathway, sphingomyelin (d17:1/14:0, d16:1/15:0), was inversely associated with both CIMT (β = -0.14, FDR-adjusted P = 0.014) and gingivitis (OR = 0.04, FDR-adjusted = 0.033).
CONCLUSIONS
The discovery of a common sphingomyelin metabolite in both disease processes is a novel finding suggesting that gingivitis and periodontitis may be associated with some overlapping metabolic pathways associated with ASCVD and indicating potential shared mechanisms among these diseases.Knowledge Transfer Statement:The same metabolites may be altered in atherosclerosis and oral disease. Specifically, a common sphingomyelin metabolite was inversely associated with gingivitis and carotid intima media thickness, a subclinical marker of atherosclerotic cardiovascular disease. These findings can provide valuable insights for future mechanistic studies to establish potential causal relationships, with the hope of influencing disease prevention and targeted early treatment.
目的
龋齿和牙周炎是全球最常见的慢性疾病,且与动脉粥样硬化性心血管疾病(ASCVD)相关。本研究旨在确定:(1)亚临床ASCVD标志物(颈动脉内膜中层厚度[CIMT]和冠状动脉钙化[CAC])与口腔疾病定量指标(包括龋失补牙数[DMFT]指数、牙龈炎参数、牙周状况和失牙数)之间的独立关联;(2)口腔疾病患者体内改变的代谢物与ASCVD患者体内改变的代谢物重叠的程度。
方法
我们使用了通过“专注于风险评估的牙科策略”项目招募的552名参与者的数据。进行了口腔检查,并测量了CIMT和CAC。在流行病学分析中,以CIMT和CAC作为因变量构建多元线性回归模型。在代谢组学分析中,使用逻辑回归或线性回归来测试1228种代谢物与每种经年龄、性别、种族、血压、吸烟、糖尿病、胆固醇、高敏C反应蛋白和白细胞介素-6校正的表型之间的关联。
结果
在完全调整的模型中,没有一种口腔疾病标志物是ASCVD标志物的显著预测因子。然而,关键脂质和脂质信号通路代谢物与牙龈炎、牙周炎和DMFT显著相关:溶血磷脂途径(比值比[OR]=2.29,错误发现率[FDR]校正=0.038)和花生四烯酸与牙龈炎相关(OR=2.35,FDR校正=0.015),鞘脂代谢途径与牙周炎相关(OR=2.09,FDR校正=0.029),缩醛磷脂和溶血磷脂途径与DMFT之间存在临界关联(P=0.055)。此外,来自鞘脂代谢途径的同一种代谢物鞘磷脂(d17:1/14:0,d16:1/15:0)与CIMT(β=-0.14,FDR校正P=0.014)和牙龈炎(OR=0.04,FDR校正=0.033)均呈负相关。
结论
在两种疾病过程中发现一种共同的鞘磷脂代谢物是一项新发现,表明牙龈炎和牙周炎可能与一些与ASCVD相关的重叠代谢途径有关,并提示这些疾病之间可能存在共同机制。知识转移声明:动脉粥样硬化和口腔疾病中可能存在相同的代谢物改变。具体而言,一种共同的鞘磷脂代谢物与牙龈炎和颈动脉内膜中层厚度呈负相关,颈动脉内膜中层厚度是动脉粥样硬化性心血管疾病的亚临床标志物。这些发现可为未来的机制研究提供有价值的见解,以建立潜在的因果关系,有望影响疾病预防和针对性的早期治疗。
相似文献
JDR Clin Trans Res. 2025-7
Cochrane Database Syst Rev. 2017-3-31
Cochrane Database Syst Rev. 2008-7-16
Cochrane Database Syst Rev. 2013-12-5
Cochrane Database Syst Rev. 2013-12-18
Cochrane Database Syst Rev. 2024-10-4
Psychopharmacol Bull. 2024-7-8
Cochrane Database Syst Rev. 2024-5-16