Tobacco smoking and perturbations in the subgingival microbial ecosystem

描述(申请人提供)：牙周炎是一种多菌感染，会破坏牙齿支撑结构，导致牙齿脱落。41.9%的牙周炎可归因于吸烟；全世界目前有12亿成年人吸烟，这种疾病是一个全球公共卫生问题。已知龈下细菌在疾病发病机制中起重要作用；然而，吸烟对这一群体的影响却知之甚少。我们的目标是测试这一假设，即吸烟优先丰富了病原体的多菌生态系统，而牺牲了健康相容的物种。我们的战略是将独特的大规模临床研究与强大的高通量分子分析、计算系统发生学和生物信息学相结合，以全面探索龈下微生物群。这种方法将弥合基于临床结果的研究和使用细菌培养和人工开发的生物膜进行的体外研究之间的差距。我们最初将结合横断面研究设计和16S rRNA基因的深度测序来识别与吸烟相关的牙周炎相关细菌。然后，我们将结合纵向临床研究和深度测序，探索龈下生物膜对戒烟的成分反应。我们将使用有针对性的、定量的分子分析来探索唾液微生物组的疾病标记和预测因素。拟议的研究将使我们更接近于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过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指标。

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.