Project 3: Exploring Tobacco Microbial Constituents and the Oral Microb

过去50年来进行的研究提供了关于无烟烟草制品、烟熏烟草制品和香烟烟雾的化学成分的大量知识。与此同时，关于烟草和烟雾中的微生物成分及其相关的不良健康影响的数据很少。然而，烟草微生物成分可能在烟草使用者的传染病和慢性病的发展中发挥重要作用。为了解决这些知识差距，本拟议项目的长期目标是利用下一代测序技术的力量，增加我们对传统、新的和新兴烟草产品的微生物成分的了解，并大大提高我们对烟草使用者中与微生物有关的健康风险的了解。该提案的具体目的如下：1）探索传统、新型和经操纵的吸烟和无烟烟草制品和烟雾的细菌微生物组，并检查特定属在烟草特异性N-亚硝胺形成中的作用; 2）为了提供新颖的，吸烟者和无烟烟草使用者与非吸烟者相比，用户;和3）表征在单次使用新的和经操作的吸烟和无烟烟草产品后口腔微生物组中的瞬时变化-细菌群落组成和表达的代谢活性。为了实现这些目标，本研究将采用一种创新的多相方法，包括在以下方面应用下一代测序方法：1）常规，新的和操作的烟草产品的时间过程实验; 2）烟草使用者和非使用者的纵向研究;和3）烟草使用者测试新的或操作的烟草产品的交叉试验。这种方法将产生丰富、新颖和有价值的数据源，FDA在实施《家庭吸烟预防和烟草控制法》并寻求改善烟草监管以造福公众健康时可以立即利用这些数据源。具体而言，这些数据可以为美国政府监管机构从未考虑过的潜在的新微生物相关烟草法规提供信息。

Research conducted over the past 50 years has provided considerable knowledge regarding the chemical constituents of smokeless tobacco products, smoked tobacco products and cigarette smoke. Meanwhile, there is a paucity of data regarding the microbial constituents of tobacco and smoke, and their associated adverse health effects. Yet, tobacco microbial constituents may play significant roles in the development of both infectious and chronic diseases among tobacco users. To address these knowledge gaps, the longterm objective of this proposed project is to harness the power of next-generation sequencing technologies to increase our understanding of the microbial constituents of conventional, new and emerging tobacco products, and greatly improve our understanding of microbial-related health risks among tobacco users. The specific aims of the proposal are as follows: 1) To explore the bacterial microbiome of conventional, new and manipulated smoked and smokeless tobacco products and smoke, and examine the role of specific genera in tobacco-specific N-nitrosamine formation; 2) To provide novel, baseline data on the composition of the oral microbiome and its associated expressed activities in smokers and smokeless tobacco users compared with that of non-users; and 3) To characterize the transient changes-bacterial community composition and expressed metabolic activities-in the oral microbiome after single-use of new and manipulated smoked and smokeless tobacco products. To accomplish these aims, this study will employ an innovative, polyphasic approach involving the application of next-generation sequencing methods in: 1) time course experiments with conventional, new and manipulated tobacco products; 2) a longitudinal study of tobacco users and nonusers; and 3) cross-over trials of tobacco users testing new or manipulated tobacco products. This approach will generate a rich, novel and valuable data source that can be immediately utilized by FDA as it implements the Family Smoking Prevention and Tobacco Control Act and seeks to improve tobacco regulation for the benefit of public health. Specifically, these data could inform potential new microbial-related tobacco regulations that have never before been considered by U.S. governmental regulators.