The Gut Microbiota, Inflammation and Cardiovascular Disease in HIV-InfectedIndividuals.

项目总结/摘要 艾滋病毒相关心血管疾病（CVD）的全球负担在过去二十年中增加了两倍， 撒哈拉以南非洲（SSA）的大部分负担。减少CVD的负担， 人口将需要坚定地了解区域特定的风险因素，特别是那些已知的调节 CVD中的炎症反应。虽然肠道细菌群落的改变（生态失调） 在健康成年人中，肠道生态失调对CVD风险的作用尚未得到很好的研究， 接受抑制性抗逆转录病毒治疗的艾滋病毒感染者。K 01提案详细介绍了一项五年计划， 候选人，博士Tecla Temu，与培训和专业知识需要评估肠道之间的关系， 在肯尼亚HIV-1研究所登记的已建立的HIV感染成人队列中， CVD研究（R21 TW 010459; PI：Farquhar）。利用粪便样本，存档的血液样本， 关于艾滋病毒感染相关因素、合并感染（潜伏性结核病、蠕虫）和早期 动脉粥样硬化疾病（颈动脉内膜中层厚度）和代谢疾病在肯尼亚的HIV-CVD研究， 该项目建议1）描述SSA中HIV感染成人的肠道微生物群，2）确定 肠道微生物群与炎症和亚临床CVD测量的关系。特姆博士的长期目标是 是一个成功的医生，科学家和独立的调查员，专注于了解 在资源有限的环境中HIV相关CVD的发病机制。她的目标是开发新的预防和 治疗方法，将改善健康的弱势群体，服务不足的人口在SSA和 在全球拟议的计划将建立在候选人的丰富经验，国际临床 和实验室研究，提高她在心血管研究方面的技能，特别是研究设计， 微生物组数据的分析和解释，以及HIV粘膜免疫学。特姆博士有很强的 华盛顿大学全球卫生系的机构支持，她目前是 临床助理教授。她的培训计划包括一个出色的指导环境， 包括艾滋病毒，心血管疾病和肠道微生物组研究的专家在SSA，它利用更多的 超过30年的福格蒂资助的研究和培训合作之间的华盛顿大学 和内罗毕大学。这种高度支持的环境将使特姆博士不仅能够完成她的使命， 提出了研究和培训目标，并成功地定位自己的独立研究生涯，但 这也使她能够充分发挥她作为华盛顿大学物理科学家的生产力和创造力的潜力 全球卫生部。

PROJECT SUMMARY/ABSTRACT The global burden of HIV associated cardiovascular disease (CVD) has tripled over the last two decades with the majority of the burden experienced in sub-Saharan Africa (SSA). Reducing the burden of CVD in this population will require a firm understanding of region-specific risk factors, particularly those known to modulate the inflammatory response involved in CVD. Although alteration of the gut bacteria communities (dysbiosis) has been linked to CVD in healthy adults, the role of gut dysbiosis on CVD risk is not well investigated among HIV-infected patients receiving suppressive ART. This K01 proposal details a five-year plan to provide the candidate, Dr. Tecla Temu, with the training and expertise needed to evaluate the relationship between gut dysbiosis and markers of early CVD in an established cohort of HIV-infected adults enrolled in the Kenya HIV- CVD study (R21 TW010459; PI: Farquhar). Taking advantage of stool specimens, archived blood samples, extensive data on HIV-infection related factors, co-infections (latent TB, helminths), and measures of early atherosclerotic disease (carotid intima media thickness) and metabolic disease in the Kenya HIV-CVD study, this project proposes to 1) characterize gut microbiota of HIV-infected adults in SSA and 2) determine the relationship of gut microbiota with measures of inflammation and subclinical CVD. Dr. Temu's long-term goal is to be a successful physician-scientist and independent investigator focused on understanding the pathogenesis of HIV-associated CVD in resource-limited settings. She aims to develop new preventive and therapeutic methods that will improve the health of disadvantaged, underserved populations in SSA and globally. The proposed program will build on the candidate's extensive experience with international clinical and laboratory research and improve her skills in cardiovascular research, specifically study design, as well as analysis and interpretation of microbiome data, and HIV mucosal immunology. Dr. Temu has strong institutional support from the University of Washington's Department of Global Health where she is currently a Clinical Assistant Professor. Her training plan incorporates an outstanding mentoring environment, one that includes experts in HIV, cardiovascular disease, and gut microbiome research in SSA, and it leverages more than 30 years of Fogarty-funded research and training collaborations between the University of Washington and University of Nairobi. This highly supportive environment will enable Dr. Temu to not only accomplish her proposed research and training goals and successfully position herself for an independent research career, but also allow her to achieve her full potential for productivity and creativity as a physician-scientist in the UW Department of Global Health.