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: 8603238
• 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/8603238
• 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; 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; deep sequencing; disorder prevention; high risk; microbial; microbial community; microbiome; never smoker; next generation sequencing; non-smoker; pathogen; pathogenic bacteria; point-of-care diagnostics; predictive modeling; pyrosequencing; 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.

描述（由申请人提供）：牙周炎是一种多数型感染，会导致牙齿支持结构的破坏并导致牙齿脱落。 41.9％的牙周炎归因于吸烟；目前在全球吸烟中有12亿名成年人，这种疾病提出了全球公共卫生问题。众所周知，尺寸细菌在疾病发病机理中起着重要作用。但是，吸烟对这个社区的影响知之甚少。我们的目标是检验以下假设，即吸烟优先富集了该多数生态系统的致病生物，而牺牲了与卫生相兼容的物种。我们的策略是将独特的大规模临床研究与稳健的高通量分子测定，计算系统发育学和生物信息学结合起来，以全面探索亚gingival微生物组。这种方法将弥合基于临床结果的研究和使用细菌培养物和人为开发的生物膜进行体外研究之间的差距。我们最初将结合16S rRNA基因的横断面研究设计，以鉴定与吸烟相关牙周炎相关的细菌。然后，我们将通过将纵向临床研究与深层测序相结合，探索尺寸生物膜对戒烟的组成反应。我们将使用靶向定量的分子测定法探索疾病标志物和预测因子的唾液微生物组。拟议的研究将使我们更加了解吸烟在牙周炎发病机理中的作用，为戒烟后为患者提供牙周治疗的生物学验证时间表，并开发唾液指标或疾病的预测指标。