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 假设上升感染是在早产的大量但未知数的基础。 阴道微生物组代表着通过 主要是乳酸属的精选生物生产乳酸。我们 假设阴道菌群缺乏足够的乳酸杆菌。 （或其他），有一个 引入致病性后，对上升感染的敏感性增强 生物体，或种子致病生物相对比例的升级（次要 正常菌群的成分在宽容状态下繁殖）。这些容易受到影响 在黑人中或从事特定的女性中，表型可能过多 破坏普通菌群的行为，例如灌肠。我们建议发现哪些因素 影响这些不利的阴道微生物组轮廓 参加了妊娠，感染和营养（PIN）研究。引脚是一个具有里程碑意义的纵向 调查黑人和白人早产的原因。从现有的 生物库，包括在妊娠24-29周收集的阴道拭子，我们建议：（1） 检查阴道微生物组与自发早产（SPTB）的关联， 并探索这些关联是否因母种族而有所不同； （2）检查 先天SPTB的危险因素，例如先天免疫基因中的母体多态性和 孕产妇的社会心理压力和抑郁症，阴道微生物组谱总体上 按种族分层； （3）检查外源危险因素对SPTB对阴道的影响 微生物组概况，例如母体营养模式，孕产妇和其他健康状况 行为。此外，作为探索性目的，我们将进行整个基因组元基因组 在富含感染性病因的PTB病例子集中进行测序，并在32之前递送 完成了几周的妊娠。更好地理解阴道之间的关系 微生物生态学和过早交付有望为初级提供新的机会 预防，并且将这些方法应用于种族多样的产前队列的时间已经成熟。