Near-Roadway and Ambient Air Pollution Exposure and the Gut Microbiome: Implications for Obesity and Insulin Resistance in Adolescence

项目概要/摘要 一个快速发展的研究领域表明，肠道微生物组与肥胖和2型糖尿病之间存在联系。 最近的研究表明，环境暴露，如近道路和环境空气污染（AAP） 暴露可影响肠道屏障完整性并改变肥胖和2型糖尿病的风险。在这项研究中，Tanya博士 Alderete建议通过以下方式研究空气污染暴露对肥胖和胰岛素抵抗风险的影响： 肠道微生物组和宏基因组。在K99指导阶段，Alderete博士将建立在现有的微生物， 健康，以及正在进行的纵向儿童健康研究（CHS）的暴露数据，该研究正在研究 南加州空气污染暴露对代谢健康的影响。她将探索 在200名青少年中使用16 S rRNA测序的近道路和AAP与肠道微生物群落结构。 博士Alderete还将分析来自非靶向宏基因组学的更复杂的微生物数据， 基因、生化途径和与空气污染暴露相关的细菌易位标记， 参与者的子集。她将推进她的环境流行病学和统计分析的知识 通过教学指导、研讨会、会议， 广泛的实践培训，以及由受人尊敬的研究人员组成的多元化咨询委员会的指导。这 多方面的培训计划将补充她在临床肥胖和2型糖尿病方面的专业知识， 具备以下方面的新技能：1）环境暴露评估（例如，近巷和AAP），2）分析技术 用于现代流行病学和3）用于微生物组研究的统计方法和研究设计。在 R 00阶段，她将通过检查细菌种类、基因和生化指标来启动一条新的研究路线。 与肥胖、胰岛素抵抗和肠道屏障完整性相关的通路。通过 利用K99阶段的结果和培训，她将揭示肥胖和肥胖之间的新关系。 胰岛素抵抗与肠道细菌种类和基因也与空气污染暴露有关。这些调查结果 这些研究将提高我们对空气增加与 污染暴露与肥胖和2型糖尿病的风险。的组成和功能的表征 在空气污染暴露的背景下，肠道微生物组对旨在减少 空气污染暴露。这项研究的结果也有可能确定新的疾病生物标志物 和针对肠道微生物组的治疗。通过这项拟议的研究，Alderete博士处于有利地位， 利用现有资源开发独立但互补的项目，旨在帮助填补 我们对近道路和AAP暴露对肠道微生物组影响的理解存在重大差距 这可能对肥胖和代谢疾病产生深远的公共卫生影响。

PROJECT SUMMARY / ABSTRACT A rapidly evolving field of study suggests a link between the gut microbiome with obesity and type 2 diabetes. Recent studies show that environmental exposures, such as near-roadway and ambient air pollution (AAP) exposure can affect gut barrier integrity and modify risk for obesity and type 2 diabetes. In this study, Dr. Tanya Alderete proposes to examine the impacts of air pollution exposure on risk for obesity and insulin resistance via the gut microbiome and metagenome. In the K99 mentored phase, Dr. Alderete will build upon existing microbial, health, and exposure data from the ongoing longitudinal Children’s Health Study (CHS), which is examining the metabolic health impacts of air pollution exposure in Southern California. She will explore relationships between near-roadway and AAP with gut microbial community structure using 16S rRNA sequencing in 200 adolescents. Dr. Alderete will also analyze more complex microbial data from untargeted metagenomics to examine microbial genes, biochemical pathways, and markers of bacterial translocation associated with air pollution exposure in a subset of participants. She will advance her knowledge of environmental epidemiology and statistical analysis techniques used to analyze exposure and microbial data through didactic instruction, seminars, conferences, extensive hands-on training, and guidance from a diverse advisory committee of respected researchers. This multifaceted training plan will complement her expertise in clinical obesity and type 2 diabetes by providing her with new skills in: 1) environmental exposure assessment (e.g., near-roadway and AAP), 2) analysis techniques used in modern epidemiology and 3) statistical methods and study design used in microbiome research. In the R00 phase, she will initiate a new line of investigation by examining bacterial species, genes, and biochemical pathways related to obesity, insulin resistance, and gut barrier integrity in the full cohort of adolescents. By utilizing results and training from the K99 phase, she will uncover novel relationships between adiposity and insulin resistance with gut bacterial species and genes also related to air pollution exposure. Findings from these studies will improve our understanding of the mechanisms underlying relationships between increased air pollution exposure with obesity and type 2 diabetes risk. Characterization of the composition and function of the gut microbiome, in the context of air pollution exposure, has implications for prevention policy directed at reducing air pollution exposure. Results from this study also have the potential to identify novel biomarkers for disease and therapies targeting the gut microbiome. With this proposed study, Dr. Alderete is well positioned to take advantage of existing resources to develop independent, yet complementary projects, designed to help to fill critical gaps in our understanding of the the impacts of near-roadway and AAP exposure on the gut microbiome that may have far-reaching public health implications for obesity and metabolic disease.