Tobacco smoking and perturbations in the subgingival microbial ecosystem

描述（由申请人提供）：牙周炎是一种多种微生物感染，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;目前全球有12亿成年人吸烟，这种疾病是一个全球性的公共卫生问题。众所周知，牙龈下细菌在疾病发病机制中发挥着重要作用;然而，人们对吸烟对该群落的影响知之甚少。我们的目标是测试这一假设，即吸烟优先丰富这个多微生物生态系统的致病生物在健康相容的物种为代价。我们的策略是将联合收割机独特的大规模临床研究与稳健的高通量分子检测、计算遗传学和生物信息学相结合，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。我们最初将联合收割机结合横断面研究设计和16 S 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与深度测序相结合，探索龈下生物膜对戒烟的组成反应。我们将使用靶向的定量分子测定来探索唾液微生物组的疾病标志物和预测因子。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，为戒烟后的牙周治疗提供生物学验证的时间表，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和龈下微生物群落之间的联系，以及这个社区对戒烟的反应。在这一高危人群中鉴定推定的病原体和健康相关细菌将使我们更接近于理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生物学验证的时间表，并开发唾液指标或疾病预测因子。

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. 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.