MATERNAL INFLAMMATION, DIET AND GUT MICROBIOME IN HIV: IMPACT ON INFANT OUTCOMES

HIV 感染中的母体炎症、饮食和肠道微生物组：对婴儿结局的影响

• 批准号: 9762133
• 负责人: Rupak Shivakoti
• 金额: $ 24.32万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-10 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9762133
• 关键词: AIDS/HIV problem; Accounting; Acute-Phase Proteins; Address; Affect; Animals; Anti-inflammatory; Award; Bacteroides; Birth; C-reactive protein; CD4 Lymphocyte Count; CD4 Positive T Lymphocytes; Cell Count; Cessation of life; Child; Child Mortality; Childhood; Communicable Diseases; Comorbidity; Competence; Consumption; Data; Data Analyses; Databases; Diet; Dietary Intervention; Dietary Practices; Dietary intake; Discipline; Disease; Educational workshop; Epidemiology; Epithelial; Exposure to; Factor Analysis; Food; Frequencies; Funding; Goals; Grant; HIV; HIV Infections; HLA-DR Antigens; Immune; Immunology; Incidence; India; Individual; Infant; Infant Health; Inflammation; Inflammatory disease of the intestine; Intake; Intestines; Learning; Link; Low Birth Weight Infant; Maternal and Child Health; Meat; Microbiology; Micronutrients; Morbidity - disease rate; National Cancer Institute; National Institute of Child Health and Human Development; Neonatal; Nutrient; Nutritional; Orosomucoid; Outcome; Parents; Pathway interactions; Perinatal; Phase; Plasma; Play; Population; Pregnancy; Pregnant Women; Premature Birth; Prevalence; Prevotella; Probiotics; Public Health; Publications; Questionnaires; Reading; Recommendation; Research; Research Personnel; Risk; Risk Factors; Role; SIV; SLEB2 gene; T-Cell Activation; Testing; Therapeutic; Training; Treatment Protocols; United States National Institutes of Health; Viral Load result; Woman; adverse outcome; antiretroviral therapy; apprenticeship; base; career; career development; co-infection; cohort; design; fruits and vegetables; gut microbes; gut microbiome; high risk; improved; indexing; infant morbidity/mortality; infant outcome; inflammatory marker; intestinal fatty acid binding protein; learning strategy; microbial; microbiome; microbiome composition; monocyte; mortality; mother nutrition; nutrition; nutritional epidemiology; pregnant; primary outcome; randomized trial; secondary outcome; skills; stool sample; symposium; zonulin

Preterm birth (PTB) is one of the leading causes of childhood morbidity and mortality. HIV-infected pregnant women have a greater incidence of PTB and this population warrants further studies to determine the risk factors. Some risk factors such as low maternal CD4 count, high viral load, co-infections, co-morbidities and treatment regimen are associated with increased preterm birth, but whether and the extent to which inflammation, a risk factor for PTB in HIV-uninfected populations, affects adverse birth outcomes among HIV- infected women remains to be studied. I am seeking the Pathway to Independence Award in order to gain additional training to meet my career goals: to become an independent investigator conducting research on maternal immune, microbiological and nutritional factors that affect maternal-child health in the context of infectious diseases, especially HIV/AIDS. In doing so, I will productively bridge the different disciplines of public health epidemiology, immunology, microbiology and nutrition. The training plan for this proposal combines various forms of learning methods including didactic courses, workshops, apprenticeships resulting in publications, directed readings and career development seminars and activities. These are designed for me to gain specific skills in: 1) Nutritional Epidemiology and Perinatal Nutrition, and 2) Microbiome data analyses. The competencies I learn from the training plan will then be applied to the research phase of the proposal (K99, and especially R00). The research component proposes to study the relationship between maternal diet, gut microbiome and inflammation and their association with PTB among HIV-infected pregnant women. Leveraging a recently funded NIH cohort immunology study of 400 HIV-infected and uninfected pregnant women, I will nest my study within this parent trial to collect dietary information and stool samples to address my specific aims: 1) Examine association between inflammation during pregnancy and incidence of adverse birth outcomes among HIV-infected pregnant women, and 2) Determine the relationship of a) dietary intake and b) gut microbiome with inflammation status among HIV-infected pregnant women. Given that diet and gut microbiome are two environmentally modifiable factors that can affect inflammation, my study will identify mechanisms to reduce inflammation and improve infant outcomes in HIV-infected populations. The proposed training and research plan will result in publications and conference presentations leading to career development to become an independent investigator during the R00 phase and with the ability to successfully compete for a R01 grant.

早产是导致儿童发病率和死亡率的主要原因之一。艾滋病病毒感染者 孕妇有更高的肺结核发病率，这一人群需要进一步研究以确定 风险因素。一些危险因素，如母亲CD4细胞计数低，病毒载量高，合并感染，合并疾病 和治疗方案与早产的增加有关，但是否和程度上 在未感染艾滋病毒的人群中，炎症是肺结核的危险因素，会影响艾滋病毒感染者的不良生育结果。 被感染的女性仍有待研究。我正在寻求独立之路奖，以获得 为实现我的职业目标而进行的额外培训：成为一名独立调查员，负责研究 影响母婴健康的孕产妇免疫、微生物和营养因素 传染病，特别是艾滋病毒/艾滋病。在这样做的过程中，我将卓有成效地在公众的不同学科之间架起桥梁 健康流行病学、免疫学、微生物学和营养学。这项建议的培训计划结合了 各种形式的学习方法，包括授课课程、研讨会、学徒制，从而 出版物、定向读物和职业发展研讨会和活动。这些都是为我设计的 掌握以下专业技能：1)营养流行病学和围产期营养，2)微生物组数据分析。 我从培训计划中学到的能力随后将应用于提案的研究阶段 (K99，特别是R00)。研究部分建议研究母体饮食、母体饮食、 HIV感染孕妇肠道菌群和炎症及其与肺结核的关系。 利用最近资助的NIH队列免疫学研究，对400名感染和未感染艾滋病毒的人进行研究 孕妇，我将在这项家长试验中嵌套我的研究，以收集饮食信息和粪便样本 解决我的具体目标：1)检查妊娠期炎症与发病率之间的关系 感染艾滋病毒的孕妇的不良分娩结局，以及2)决定a)饮食的关系 (B)感染艾滋病毒的孕妇的肠道微生物群与炎症状态。考虑到这种饮食习惯 和肠道微生物群是两个环境可改变的因素，可以影响炎症，我的研究将 在艾滋病毒感染人群中确定减少炎症和改善婴儿结局的机制。这个 拟议的培训和研究计划将导致出版物和会议演讲导致职业生涯 发展成为R00阶段的独立调查员，并有能力成功 争夺R01奖助金。