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

项目摘要/摘要 一个快速发展的研究领域表明，肠道微生物群与肥胖和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) 暴露会影响肠道屏障的完整性，并降低肥胖和2型糖尿病的风险。在这项研究中，坦尼娅博士 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 肠道微生物组和元基因组组。在K99指导阶段，Alderete博士将建立在现有微生物的基础上， 健康，以及来自正在进行的纵向儿童健康研究(CHS)的暴露数据，该研究正在审查 南加州空气污染暴露对代谢健康的影响。她将探索两人之间的关系 应用16S rRNA测序对200名青少年进行肠道微生物群落结构分析。 Alderete博士还将分析来自非靶向元基因组学的更复杂的微生物数据，以检查微生物 与空气污染暴露相关的细菌易位的基因、生化途径和标志物 参与者的子集。她将提高环境流行病学和统计分析方面的知识 用于分析暴露和微生物数据的技术，通过教学、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样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症和2型糖尿病方面的专业知识，为她提供 具备以下方面的新技能：1)环境暴露评估(例如，近路和AAP)，2)分析技术 用于现代流行病学；3)用于微生物组研究的统计方法和研究设计。在 在R00阶段，她将通过检查细菌种类、基因和生化来启动一项新的调查 在整个青少年队列中与肥胖、胰岛素抵抗和肠道屏障完整性相关的途径。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。来自这些的发现 研究将提高我们对空气增加之间潜在关系的机制的理解 污染暴露与肥胖和2型糖尿病风险。组织的组成和功能的表征 在空气污染暴露的背景下，肠道微生物群对旨在减少 暴露在空气污染中。这项研究的结果也有可能识别疾病的新生物标记物。 以及针对肠道微生物群的治疗。有了这项拟议的研究，阿尔德雷特博士很好地采取了 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暴露对肠道微生物群影响的认识上的关键差距 这可能会对肥胖和代谢性疾病产生深远的公共健康影响。

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.