Metabolic Syndrome, Periodontal Health, and the Oral Microbiome

代谢综合征、牙周健康和口腔微生物组

• 批准号: 10372351
• 负责人: Sukirth Murthy Ganesan
• 金额: $ 15.45万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-15 至 2024-01-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10372351
• 关键词: Adult; Affect; American; Area; Bacteria; Biochemical; Biological Markers; Cardiovascular Diseases; Case-Control Studies; Clinical; Complex; Control Groups; Cross-Sectional Studies; Data; Development; Diagnosis; Disease; Early Intervention; Economics; Ecosystem; Environment; Epidemic; Foundations; Future; Genes; Goals; Health; Homeostasis; Immune; Individual; Investigation; Knowledge; Lead; Longitudinal Studies; Maps; Mass Fragmentography; Metabolic; Metabolic Control; Metabolic Pathway; Metabolic syndrome; Metabolism; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Oral; Oral cavity; Oral health; Oral mucous membrane structure; Order Spirochaetales; Outcome; Pathogenicity; Pathway interactions; Patients; Periodontal Diseases; Periodontitis; Periodontium; Physiological; Population; Predisposition; Prevalence; Reporting; Research Design; Risk; Role; Selenomonas; Severities; Site; Systems Biology; Testing; Tooth Loss; Treatment Cost; Treponema; Volatile Fatty Acids; adverse outcome; arm; base; chronic inflammatory disease; clinical epidemiology; cohort; cost estimate; dysbiosis; gene product; genome sequencing; healthy weight; high risk; metagenome; metagenomic sequencing; microbial; microbial colonization; microbial composition; microbiome; obese person; oral microbiome; small molecule; statistics; whole genome

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.

项目概要 代谢综合征 (MetS)，一种影响超过 1/3 的美国成年人的全球流行病 人群，是一组容易出现类型的生化和生理异常 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) 是肥胖的一种不良后果，与体重增加有关 牙周炎的范围和严重程度。牙周炎是一种由微生物引起的慢性牙周炎 炎症性疾病会破坏牙齿的支撑结构，最终导致牙齿脱落 损失和严重的疾病影响了约 10% 的美国成年人。虽然有 叙述性评论和一些横断面研究表明， MetS 和牙周炎患病率增加，这些关联背后的机制 尚未被调查。 口腔环境的菌群失调会导致牙周病，但其机制 MetS 患者口腔微生物组的这些破坏和随后的功能改变 保持未定义。因此，我们的中心假设是 MetS 造成了一种有伤害的风险 环境，甚至在临床牙周病发病之前，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： 具体目标 1、我们将通过比较和量化来确定 MetS 对口腔宏基因组的影响 MetS 和 MetS 之间微生物基因丰度和相关功能途径的变化 对照，使用多臂、横断面研究设计和全宏基因组测序。在 具体目标 2 我们将绘制微生物衍生代谢物（最终产品）的图谱 使用气相色谱/质谱分析 MetS 患者的龈下环境 (GC/MS) 分析。拟议研究的预期结果是确定 MetS 对龈下环境功能和代谢景观的影响。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 为今后的机理研究奠定基础。在令人震惊的统计数据的推动下 在流行病盛行的背景下，MetS 造成的经济和健康负担 针对美国成年人的牙周病，我们提出了一项急需的研究 严重未开发的领域：代谢综合征对口腔健康的影响。我们的长期 术语目标是确定个性化的、经过实验验证的生物标志物/潜在指标 这个高风险人群的健康状况和未来的牙周病。