Tobacco smoking and perturbations in the subgingival microbial ecosystem

描述（由申请人提供）：牙周炎是一种多微生物感染，可导致牙齿支撑结构破坏并导致牙齿脱落。41.9%的牙周炎可归因于吸烟；目前全世界有12亿成年人吸烟，这种疾病已成为一个全球性的公共卫生问题。已知牙龈下细菌在疾病发病机制中起重要作用；然而，人们对吸烟对这个群体的影响知之甚少。我们的目标是验证这样一个假设，即吸烟优先丰富了致病生物的多微生物生态系统，而牺牲了健康相容的物种。我们的策略是将独特的、大规模的临床研究与强大的、高通量的分子分析、计算系统发育和生物信息学相结合，以全面探索牙龈下微生物组。这种方法将弥合基于临床结果的研究和使用细菌培养和人工开发的生物膜的体外研究之间的差距。我们将首先结合横断面研究设计和16S rRNA基因的深度测序来鉴定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和深度测序相结合，探索牙龈下生物膜对戒烟的组成反应。我们将使用一种靶向的、定量的分子分析来探索唾液微生物组的疾病标志物和预测因子。这些研究将使我们进一步了解吸烟在牙周炎发病机制中的作用，为戒烟后患者进行牙周治疗提供生物学验证的时间表，并开发疾病的唾液指标或预测因子。

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.