Metabolic Syndrome, Periodontal Health, and the Oral Microbiome

项目摘要 代谢综合征(METS)，一种影响超过三分之一美国成年人的全球流行病 群体，是一组生化和生理异常，易患T型 2糖尿病(T2D)和心血管疾病(CVD)。新出现的证据表明 代谢综合征(METS)是肥胖的不良后果，与体重增加有关 牙周炎的程度和严重程度。牙周炎是由微生物引起的慢性牙周炎。 一种炎症性疾病，破坏牙齿的支撑结构，最终导致牙齿 这种疾病的损失和严重形式影响了大约10%的美国成年人。尽管有 叙事性综述和一些横断面研究表明， 蛋氨酸与牙周炎患病率的增加，这些联系背后的机制(S) 还没有被调查。 口腔环境中的生物失调导致牙周病，然而，其机制 甲型肝炎患者口腔微生物组中的这些干扰和随后的功能变化 仍然没有定义。因此，我们的中心假设是，METS产生了一种危险的伤害 环境，甚至在临床牙周病发作之前通过改变微生物 功能和代谢物。我们将通过实现两个目标来检验我们的假设：在特定目标中 1、我们将通过比较和量化来确定蛋氨酸对口腔后基因组的影响 Met和Met之间微生物基因丰度和相关功能途径的变化 对照，采用多臂横断面研究设计，全基因组测序。在……里面 具体目标2我们将绘制微生物衍生的代谢物(最终产品)在 气相色谱/质谱法测定甲硫氨酸转移症患者的龈下环境 (GC/MS)分析。拟议研究的预期结果是确定 甲硫氨酸对龈下环境功能和代谢格局的影响。我们 预计我们的综合系统生物学方法与临床流行病学相结合将 为今后的机械化调查奠定基础。由令人震惊的统计数据驱动的 在艾滋病流行的背景下大都会医院造成的经济和卫生负担 在美国成年人中的牙周病，我们在一项急需的研究中提出了一项 严重开发不足的地区：代谢综合征对口腔健康的影响。我们的长- 术语目标是确定个性化的、经过实验验证的生物标记物/潜在指标 在这个高危队列中的健康和未来的牙周病。

Project Summary Metabolic syndrome (MetS), a global epidemic that affects more than 1/3rd of the US adult population, is a cluster of biochemical and physiological abnormalities that predisposes to Type 2 Diabetes (T2D) and Cardiovascular Diseases (CVD). Emerging evidence indicates that Metabolic Syndrome (MetS), an adverse consequence of obesity, is associated with an increase in the extent and severity of periodontitis. Periodontitis is a microbially induced chronic inflammatory disease that destroys the supporting structures of teeth, eventually leading to tooth loss and the severe form of the disease affects ~10% of the American adults. Although there are narrative reviews and a handful of cross-sectional studies that suggest the association between MetS and increased prevalence of periodontitis, the mechanism(s) behind these associations have not been investigated. Dysbiosis in the oral environment leads to periodontal disease, however, the mechanisms of these disruptions and subsequent functional alterations in the oral microbiome of MetS patients remain undefined. Therefore, our central hypothesis is that MetS creates an at-risk-for-harm environment, even before the onset of clinical periodontal disease by altering the microbial functions and metabolites. We will test our hypothesis by carrying out two aims: In Specific Aim 1, we will determine the effects of MetS on the oral metagenome, by comparing and quantifying changes in microbial gene abundances and associated functional pathways between MetS and controls, using a multi-arm, cross-sectional study design with whole-metagenome sequencing. In Specific Aim 2 we will map the microbially-derived metabolites (the end products) in the subgingival environment of patients with MetS using gas chromatography/mass spectrometry (GC/MS) analysis. The expected outcomes of the proposed studies are the determination of effects of MetS on the functional and metabolic landscape of the subgingival environment. We anticipate that our integrative systems biology approach combined with clinical epidemiology will lay the foundation for future mechanistic investigations. Driven by the startling statistics of economic and health burden caused by the MetS in the backdrop of the prevalence of the periodontal disease in the US adult population, we are proposing a much-needed study in a severely under-explored area: the impact of Metabolic Syndrome on oral health. Our long- term goal is to identify personalized, experimentally validated biomarkers/potential indicators of health and future periodontal disease in this high-risk cohort.