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

项目摘要/摘要 全球艾滋病毒相关心血管疾病(CVD)的负担在过去20年中增加了两倍， 大部分负担发生在撒哈拉以南非洲(SSA)。减轻心血管疾病在这方面的负担 人口将需要对特定地区的风险因素有深刻的了解，特别是那些已知的调节因素 炎症反应参与了CVD的发生。虽然肠道细菌群落的变化(生物失调) 已经与健康成年人的心血管疾病有关，但肠道生物失调对心血管疾病风险的作用尚未得到很好的研究 艾滋病毒感染者接受抑制性抗逆转录病毒治疗。这份K01提案详细说明了一个五年计划，以提供 候选人，Tecla Temu博士，具有评估肠道之间关系所需的培训和专业知识 肯尼亚HIV-HIV登记的HIV感染成人队列中的生物失调和早期心血管疾病标志物 CVD研究(R21 TW010459；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、混合感染(潜伏结核病、蠕虫)和早期监测措施的大量数据 肯尼亚HIV-CVD研究中的动脉粥样硬化性疾病(颈动脉内膜中层厚度)和代谢性疾病 该项目建议1)描述SSA中感染艾滋病毒的成年人的肠道微生物区系，2)确定 肠道微生物区系与炎症指标和亚临床心血管疾病的关系。特姆博士的长期目标 是成为一名成功的内科科学家和独立调查者，专注于理解 在资源有限的情况下艾滋病毒相关心血管疾病的发病机制。她的目标是开发新的预防和 治疗方法将改善SSA和SSA中弱势、未得到充分服务的人群的健康 全球范围内。拟议的计划将建立在候选人在国际临床方面的丰富经验的基础上 和实验室研究，并提高她在心血管研究方面的技能，特别是研究设计，以及 微生物组数据的分析和解释，以及艾滋病毒粘膜免疫学。特姆医生有很强的 来自华盛顿大学全球卫生系的机构支持，她目前在那里 临床助理教授。她的培训计划包含了一个出色的指导环境，一个 包括SSA的艾滋病毒、心血管疾病和肠道微生物组研究方面的专家，它利用了更多 30多年来，华盛顿大学与福格蒂资助的研究和培训合作 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实现她的目标 提出了研究和培训目标，并成功地定位了自己的独立研究生涯，但 也使她能够充分发挥她作为威斯康星州内科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.