E-cigarettes and perturbations in the subgingival ecosystem

电子烟和龈下生态系统的扰动

• 批准号: 9765271
• 负责人: Purnima Kumar
• 金额: $ 67.27万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-16 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9765271
• 关键词: Acute; Address; Adolescent and Young Adult; Aerosols; Affect; Algorithmic Analysis; Algorithms; Animal Model; Area; Bacteria; Bacterial Genes; Bioinformatics; Biological; Biological Markers; Biological Models; Centers for Disease Control and Prevention (U.S.); Characteristics; Child; Chronic; Cigarette; Clinical; Clinical Research; Communities; Custom; Cytotoxic agent; Data; Disease; Ecosystem; Electronic Nicotine Delivery Systems; Electronic cigarette; Elements; Entropy; Equilibrium; Event; Exposure to; Flavoring; Formulation; Gene Expression; Gingival Crevicular Fluid; Glycerol; Goals; Gold; Graph; Health; Homeostasis; Human; Immune response; Immunity; In Vitro; Individual; Inflammatory Response; Investigation; Juice; Knowledge; Legal; Maps; Measures; Metagenomics; Methodology; Mucous Membrane; Nicotine; Observational Study; Oral; Oral cavity; Oral health; Oral mucous membrane structure; Outcome; Pathogenicity; Pathway Analysis; Perception; Periodontitis; Phase; Physiological; Placebos; Propylene Glycols; Reporting; Research; Research Design; Risk; Risk Assessment; Role; Smoking; Structure; System; Systems Biology; Testing; Time; TimeLine; Tobacco smoking behavior; United States; Validation; Virulence; arm; base; beta diversity; catalyst; clinical epidemiology; cohort; dosage; dysbiosis; electronic cigarette use; electronic cigarette user; high school; host-microbe interactions; immunogenic; improved; in vitro Model; in vivo; metatranscriptome; metatranscriptomics; microbial; microbial host; microbiome; multilevel analysis; mutualism; nicotine replacement; novel; oral bacteria; oral microbiome; pathogen; response; smoking cessation; subgingival microbiome; tobacco products; tool; transcriptome; transcriptome sequencing; transcriptomics; vaping; young adult

Despite having been introduced ten years ago, little is known of the impact of electronic nicotine delivery systems (ENDS or e-cigarettes or e-cigs) on human health. ENDS usage is rapidly rising among adolescents and young adults and this is partially due to a perception that e-cigs are safer than cigarettes and other nicotine replacement therapies. However, these products vary widely in nicotine content, propylene glycol, glycerol, additives and flavorings; all of which are poorly studied. Therefore, there is an urgent need for biological investigations that will improve our understanding of how ENDS impact human health. The initial point of contact of ENDS, and the first-affected system in humans is the oral cavity. It is known that nicotine impacts oral health, acting as a cytotoxic agent as well as increasing virulence of certain bacteria. Oral health is dependent upon an intricate balance between the microbial ecosystem and host immunity. Based on our preliminary studies that ENDS alter the compositional structure and the functional potential of the oral ecosystem, we hypothesize that e-cigs will impact this microbial-mucosal homeostasis. We propose to test this hypothesis by combining novel clinical study designs with integrated `-omics' approaches and computational bioinformatics. This approach will bridge the gap between purely clinical outcome-based studies, in vitro investigations and in vivo investigations using animal models. First, the biological effects of different formulations of ENDS on an in vitro model of the oral host-microbial interactome will be examined through dual transcriptome-metatranscriptome sequencing. Second, we will observe the effects of ENDS on host-bacterial interactions over time by combining a multi-arm, longitudinal clinical study with a network analysis algorithm. The proposed studies will bring us closer to understanding the role of ENDS in disrupting oral ecological homeostasis, provide biologically-validated timelines for assessing risk associated with ENDS use, and develop indicators or predictors of exposure.

尽管电子尼古丁在十年前就已推出，但人们对它的影响却知之甚少。 传输系统（电子烟或电子香烟）对人类健康的影响。 ENDS 的使用率正在迅速上升 青少年和年轻人，部分原因是电子烟比香烟更安全， 其他尼古丁替代疗法。然而，这些产品的尼古丁含量、丙烯含量差异很大。 乙二醇、甘油、添加剂和调味剂；所有这些都没有得到很好的研究。因此，迫切需要 生物学研究将提高我们对电子尼古丁传送系统如何影响人类健康的理解。最初的 ENDS 的接触点，人体首先受影响的系统是口腔。据了解，尼古丁 影响口腔健康，充当细胞毒剂并增加某些细菌的毒力。口腔健康 取决于微生物生态系统和宿主免疫力之间的复杂平衡。基于我们的 初步研究表明 ENDS 改变了口腔的成分结构和功能潜力 生态系统中，我们假设电子烟将影响这种微生物粘膜稳态。我们建议对此进行测试 通过将新颖的临床研究设计与集成的“组学”方法和计算相结合的假设 生物信息学。这种方法将弥合纯粹基于临床结果的研究与体外研究之间的差距 使用动物模型进行研究和体内研究。一、不同的生物效应 口腔宿主-微生物相互作用体外模型上的 ENDS 配方将通过双重检查进行检查 转录组-宏转录组测序。其次，我们将观察ENDS对宿主细菌的影响 通过将多臂纵向临床研究与网络分析算法相结合，随着时间的推移进行交互。 拟议的研究将使我们更深入地了解 ENDS 在破坏口腔生态方面的作用 稳态，提供经过生物学验证的时间表来评估与 ENDS 使用相关的风险，以及 制定暴露指标或预测指标。