Modulation of oral microenvironment by E-cigarette aerosol mixtures

电子烟气溶胶混合物调节口腔微环境

• 批准号: 9236180
• 负责人: Xin Li
• 金额: $ 40.19万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2020-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9236180
• 关键词: Address; Adverse effects; Aerosols; Affect; Age; Air; Aldehydes; Bacteria; Biological Markers; Breathing; Cell Survival; Cells; Chemicals; Cigarette; Cigarette Smoker; Clinical; Clinical Research; Complex; Control Groups; Cultured Cells; Cytokine Gene; Data; Electronic cigarette; Employee Strikes; Enrollment; Epithelial Cells; Exhalation; Gene Expression; Genes; Glycine; Growth; Guidelines; Harvest; Health; Homeostasis; Human body; IL8 gene; Impairment; In Vitro; Individual; Inflammation Mediators; Inflammatory; Interferon Type II; Interleukin-1 beta; Interleukin-10; Interleukin-12; Interleukin-13; Interleukin-6; Interruption; Learning; Liquid substance; Marketing; Measures; Metagenomics; Metals; Monitor; National Institute of Dental and Craniofacial Research; Nicotine; Nitrosamines; Oral; Oral cavity; Oral health; Outcome; Pathway interactions; Periodontal Diseases; Poison; Policies; Porphyromonas gingivalis; Production; Prospective Studies; Public Health; RNA; Recruitment Activity; Regulation; Research Design; Research Priority; Ribosomal RNA; Risk; Safety; Saliva; Salivary; Sampling; Series; Smoke; Smoker; Smoking; TNF gene; Time; Tissue Model; Tissues; Tobacco; Tobacco smoke; Tobacco use; Toxic effect; Transcript; United States National Institutes of Health; Virulence; Visit; addiction; base; chemokine; co-infection; college; cytokine; dentilisin; design; evidence base; gingipain; improved; microbiome; microorganism; non-smoker; novel; oral bacteria; oral cavity epithelium; oral microbiome; pathogen; public health relevance; volatile organic compound

 DESCRIPTION (provided by applicant): The popularity of electronic cigarettes (E-cigarettes) is increasing worldwide. Marketing strategies have suggested that E-cigarettes can be used by tobacco smokers to help them quit, however, recent studies from 8 U.S. colleges indicate that 17% of E-cigarette users had never smoked a conventional cigarette. Each E-cigarette can provide 200-400 puffs, without interruption, which is equivalent to 2-3 packs of cigarettes. Nicotine, the main ingredient in E-cigarettes aerosol and at high concentration it is toxic and addictive. Given that E-cigarette aerosol may contain other harmful toxic compounds, regulatory agencies recommend caution in the use of E-cigarettes until their safety is better evaluated and documented. The initial interaction of E-cigarette aerosol mixtures occurs largely in the oral cavity, where nicotine and other compounds are expected to be most active and the exposure is most intense. Our preliminary data using commercially available E-cigarettes, demonstrate that the effects of E-cigarette aerosol on epithelial cells are profound. The effect of E-cigarette aerosol on the oral microbiome was significant as our 16S rRNA sequencing detected a shift in the salivary bacterial profile. Inflammatory mediators associated with periodontal health were higher in E-cigarette users than in nonsmokers. Furthermore, in vitro studies using a novel Electronic Cigarette Aerosol Generator (ECAG) and epithelial cells demonstrated that levels of transcripts that encode cytokines and chemokines were significantly higher in the group of cells which were first challenged by Porphyromonas gingivalis and then exposed to the E-cigarette aerosol than in cells exposed to either P. gingivalis only or P. gingivalis and air. These data suggest that E-cigarette aerosol can alter the homeostasis of the oral cavity through its direct effects on epigingival tissue and the oral microbiome. We hypothesize that E-cigarette aerosol mixtures disrupts the homeostasis of the oral microenvironment by altering the composition of the oral microbiome and increasing the expression of inflammatory mediators. We will conduct clinical and in vitro mechanistic studies in two integrated Specific Aims. In Specific Aim 1, we propose to conduct a prospective study in which we will enroll 120 age-matched subjects (40 in each of 3 groups: control nonsmokers, only tobacco smokers, and only E-cigarette users) to determine the effects of E-cigarettes aerosol on the oral microbiome and inflammatory mediators associated with periodontal disease. In Specific Aim 2, we will use a 3D epigingival tissue model with an ECAG to determine the impact of E-cigarette aerosols on epigingival tissue and inflammatory mediators when challenged by periodontal pathogens. We will apply novel clinical and in vitro approaches to reveal the oral health impact of E-cigarettes, which will address the research priorities of the NIH-NIDCR. This is the first comprehensive study designed specifically to identify microbiome and periodontal disease biomarkers for measuring and monitoring the adverse health effects of E-cigarette aerosol mixtures and for filling gaps in our understanding of the potential risks associated with E-cigarettes.

 描述（由申请人提供）：电子烟（E-香烟）在全球范围内越来越受欢迎。营销策略表明，吸烟者可以使用电子烟来帮助他们戒烟，然而，美国 8 所大学最近的研究表明，17% 的电子烟使用者从未吸过传统香烟。每支电子烟可不间断地吸200-400口，相当于2-3包香烟。尼古丁是电子烟气雾剂中的主要成分，高浓度时具有毒性和成瘾性。鉴于电子烟气溶胶可能含有其他有害的有毒化合物，监管机构建议谨慎使用电子烟，直到其安全性得到更好的评估和记录。电子烟气溶胶混合物的最初相互作用主要发生在口腔中，预计尼古丁和其他化合物在口腔中最活跃并且暴露最强烈。我们使用市售电子烟​​的初步数据表明，电子烟气溶胶对上皮细胞的影响是深远的。电子烟气雾剂对口腔微生物组的影响非常显着，因为我们的 16S rRNA 测序检测到唾液细菌谱发生了变化。电子烟使用者中与牙周健康相关的炎症介质高于不吸烟者。此外，使用新型电子烟气溶胶发生器（ECAG）和上皮细胞的体外研究表明，首先受到牙龈卟啉单胞菌攻击然后暴露于电子烟气溶胶的细胞组中，编码细胞因子和趋化因子的转录物水平显着高于仅暴露于牙龈卟啉单胞菌或暴露于牙龈卟啉单胞菌和空气的细胞。这些数据表明，电子烟气雾剂可以通过对牙龈组织和口腔微生物组的直接影响来改变口腔的稳态。我们假设电子烟气雾混合物通过改变口腔微生物组的组成并增加炎症介质的表达来破坏口腔微环境的稳态。我们将针对两个综合具体目标进行临床和体外机制研究。在具体目标 1 中，我们建议进行一项前瞻性研究，其中我们将招募 120 名年龄匹配的受试者（3 组中每组 40 名：对照非吸烟者、仅吸烟者和仅电子烟使用者），以确定电子烟气雾剂对口腔微生物组和与牙周病相关的炎症介质的影响。在具体目标 2 中，我们将使用带有 ECAG 的 3D 牙龈组织模型来确定电子烟气溶胶在受到牙周病原体攻击时对牙龈组织和炎症介质的影响。我们将应用新的临床和体外方法来揭示电子烟对口腔健康的影响，这将解决 NIH-NIDCR 的研究重点。这是第一项专门设计用于确定微生物组和牙周病生物标志物的综合研究，用于测量和监测电子烟气雾混合物对健康的不利影响，并填补我们对电子烟相关潜在风险的理解空白。