The Vaginal Microbiome and Racial Disparity in Preterm Delivery

阴道微生物组和早产的种族差异

• 批准号: 9241046
• 负责人: Stephanie Engel
• 金额: $ 45.08万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-02-01 至 2021-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9241046
• 关键词: Address; Area; Behavior; Behavioral; Bioinformatics; Biological Markers; Black race; Classification; Clinical; Communities; Data; Databases; Dietary Practices; Ecology; Enrollment; Epidemiology; Ethnic Origin; Etiology; Genes; Genetic; Genetic Markers; Genetic Polymorphism; Genetic Variation; Genotype; Habitats; Health Priorities; Health behavior; Human Microbiome; Infection; Infectious Pregnancy Complications; Investigation; Lactic acid; Lactobacillus; Medical; Mental Depression; Methodology; Methods; Minor; Molecular; Natural Immunity; Nutritional; Organism; Pathogenicity; Patient Self-Report; Pattern; Perinatal; Phenotype; Physiological; Predisposition; Pregnancy; Premature Birth; Premature Labor; Premature Rupture Fetal Membranes; Prevention; Primary Prevention; Production; Prospective Studies; Psychosocial Stress; Race; Risk; Risk Factors; Sampling; Seeds; Sex Behavior; Swab; Technology; Time; United States National Institutes of Health; Vagina; Vaginal Douching; Woman; Xenobiotics; base; biobank; cohort; fetal medicine; interest; maternal cigarette smoking; metagenomic sequencing; microbial; microbiome; microbiota; modifiable risk; next generation sequencing; novel; nutrition; permissiveness; premature; prenatal; psychologic; racial disparity; racial diversity; social; vaginal microbiome; whole genome

Project Summary Ascending infection is hypothesized to underlie a large but unknown fraction of preterm births. The vaginal microbiome represents a physiological barrier to ascending infection through the production of lactic acid by select organisms principally of the Lactobacillus genus. We hypothesize that vaginal microbiota lacking sufficient Lactobacillus spp. (or others), have a heightened susceptibility to ascending infection following the introduction of pathogenic organisms, or the escalation in the relative proportion of seed pathogenic organisms (minor constituents of the normal flora that multiply in permissive states). These susceptible phenotypes may be over-represented among Blacks, or among women practicing specific behaviors that disrupt the normal flora, like douching. We propose to discover what factors influence these unfavorable vaginal microbiome profiles in an existing, diverse cohort of women enrolled in the Pregnancy, Infection and Nutrition (PIN) study. PIN is a landmark longitudinal investigation of the causes of prematurity among Blacks and Whites. Drawing from an existing biobank including vaginal swabs collected at 24-29 weeks' gestation, we propose to: (1) Examine the associations of the vaginal microbiome with spontaneous preterm birth (sPTB), and explore whether these associations differ by maternal race; (2) Examine the influence of innate sPTB risk factors, such as maternal polymorphisms in innate immunity genes and maternal psychosocial stress and depression, on vaginal microbiome profiles overall and stratified by race; and, (3) Examine the influence of exogenous risk factors for sPTB on vaginal microbiome profiles, such as maternal nutritional patterns, maternal smoking, and other health behavior. Furthermore, as an exploratory aim, we will conduct whole genome metagenome sequencing in a subset of PTB cases enriched for an infectious etiology, with delivery before 32 completed weeks' gestation. A better understanding of the relationship between vaginal microbial ecology and premature delivery is poised to offer new opportunities for primary prevention, and the time is ripe to apply these methods to a racially diverse prenatal cohort.

项目摘要 上升感染被认为是早产的一大部分但未知的基础。 阴道微生物群代表着一种生理屏障，通过 主要由乳杆菌属的精选生物产生乳酸。我们 假设阴道微生物区系缺乏足够的乳杆菌属。(或其他人)，有一个 在引入致病因子后，对上行感染的易感性增加 生物体，或种子病原生物体(次要)相对比例的上升 在允许状态下繁殖的正常植物区系的成分)。这些易受影响的 表型在黑人或从事特定职业的女性中可能过多。 扰乱正常菌群的行为，如冲洗。我们建议发现是什么因素 在现有的不同的女性队列中影响这些不利的阴道微生物组特征 参加怀孕、感染和营养(PIN)研究。大头针是纵向的标志性建筑 黑人和白人早产原因的调查。从现有的 生物库，包括在怀孕24-29周收集的阴道拭子，我们建议：(1) 检查阴道微生物群与自发早产的关系， 并探讨这些关联是否因母系种族而不同；(2)检验 先天肺结核危险因素，如母体先天免疫基因和 母亲心理社会压力和抑郁，对阴道微生物组的总体和 按种族分层；以及，(3)检查外源性肺结核危险因素对阴道的影响 微生物组概况，如产妇营养模式、产妇吸烟和其他健康 行为。此外，作为一个探索性目标，我们将进行全基因组元基因组学 在32岁之前分娩的感染病原学丰富的肺结核病例中的一组病例的测序 完成了几周的孕期。更好地理解阴道病与阴道病的关系 微生物生态和早产有望为初级保健提供新的机遇 预防，将这些方法应用于不同种族的产前队列的时机已经成熟。