Tobacco smoking and perturbations in the subgingival microbial ecosystem

吸烟和龈下微生物生态系统的扰动

• 批准号: 8273549
• 负责人: Purnima Kumar
• 金额: $ 38.13万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-13 至 2017-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8273549
• 关键词: Adult; Affect; Age-Years; Area; Bacteria; Bioinformatics; Biological; Biological Assay; Clinical; Clinical Research; Communities; Coronary heart disease; Cross-Sectional Studies; Diabetes Mellitus; Disease; Disease Marker; Ecosystem; Epidemiologic Studies; Fingerprint; Goals; Health; Health Status; Hour; In Vitro; Individual; Infection; Investigation; Knowledge; Large-Scale Sequencing; Life; Metric; Microbial Biofilms; Modeling; Molecular; Organism; Outcome; Outcome Study; Pathogenesis; Patients; Periodontal Diseases; Periodontitis; Periodontium; Phylogenetic Analysis; Play; Population; Public Health; Recombinant DNA; Relative (related person); Research; Research Design; Resolution; Role; Salivary; Sampling; Smoker; Smoking; Structure; Testing; Therapeutic Intervention; TimeLine; Tobacco smoking; Tooth Loss; Tooth structure; Treatment outcome; base; cerebrovascular; cohort; disorder prevention; high risk; microbial; microbial community; microbiome; next generation; non-smoker; pathogen; pathogenic bacteria; point-of-care diagnostics; predictive modeling; rRNA Genes; response; smoking cessation; statistics; subgingival biofilm

DESCRIPTION (provided by applicant): Periodontitis is a polymicrobial infection that causes destruction of tooth-supporting structures and results in tooth loss. 41.9% of periodontitis is attributable to smoking; and with 1.2 billion adults worldwide currently smoking, this disease presents a global public health issue. Subgingival bacteria are known to play an important role in disease pathogenesis; however, the effects of smoking on this community are poorly understood. Our goal is to test the hypothesis that smoking preferentially enriches this polymicrobial ecosystem for pathogenic organisms at the expense of health-compatible species. Our strategy is to combine unique, large-scale clinical studies with robust, high-throughput molecular assays, computational phylogenetics and bioinformatics for a comprehensive exploration of the subgingival microbiome. This approach will bridge the gap between clinical outcome-based studies and in vitro investigations using bacterial cultures and artificially developed biofilms. We will initially combine a cross-sectional study design with deep sequencing of 16S rRNA genes to identify bacteria associated with smoking-related periodontitis. We will then explore the compositional responses of the subgingival biofilm to smoking cessation by combining a longitudinal clinical study with deep sequencing. We will use a targeted, quantitative molecular assay to explore the salivary microbiome for disease markers and predictors. The proposed studies will bring us closer to understanding the role of smoking in the pathogenesis of periodontitis, provide biologically-validated timelines for administering periodontal therapy to patients following smoking cessation, and develop salivary indicators or predictors of disease. PUBLIC HEALTH RELEVANCE: These studies represent the first comprehensive approach to examine the association between smoking and the subgingival microbial community as well as the response of this community to smoking cessation. Identification of putative pathogens and health- associated bacteria in this high-risk population will bring us closer to understanding the role of smoking in the pathogenesis of periodontitis, provide biologically-validated timelines for administering periodontal therapy to patients following smoking cessation, and develop salivary indicators or predictors of disease.

描述（由申请人提供）：牙周炎是一种多种微生物感染，会导致牙齿支撑结构破坏并导致牙齿脱落。 41.9%的牙周炎与吸烟有关；目前全球有 12 亿成年人吸烟，这种疾病构成了全球公共卫生问题。众所周知，龈下细菌在疾病发病机制中发挥着重要作用。然而，人们对吸烟对这个社区的影响知之甚少。我们的目标是检验这样的假设：吸烟优先丰富病原微生物的多微生物生态系统，而牺牲健康兼容的物种。我们的策略是将独特的大规模临床研究与强大的高通量分子测定、计算系统发育学和生物信息学相结合，以全面探索龈下微生物组。这种方法将弥合基于临床结果的研究与使用细菌培养物和人工开发的生物膜的体外研究之间的差距。我们首先将横断面研究设计与 16S rRNA 基因深度测序相结合，以识别与吸烟相关的牙周炎相关的细菌。然后，我们将通过纵向临床研究与深度测序相结合，探索龈下生物膜的成分对戒烟的反应。我们将使用有针对性的定量分子检测来探索唾液微生物组的疾病标记物和预测因子。拟议的研究将使我们更深入地了解吸烟在牙周炎发病机制中的作用，为戒烟后的患者提供经生物学验证的牙周治疗时间表，并开发唾液指标或疾病预测因子。 公共卫生相关性：这些研究代表了第一个全面的方法来检查吸烟与龈下微生物群落之间的关联以及该群落对戒烟的反应。鉴定这一高危人群中假定的病原体和健康相关细菌将使我们更深入地了解吸烟在牙周炎发病机制中的作用，为戒烟后的患者进行牙周治疗提供经过生物学验证的时间表，并制定唾液指标或疾病的预测因子。