Vaginal Microbiome and Metabolites in Preterm Birth

早产中的阴道微生物组和代谢物

• 批准号: 10192909
• 负责人: Anna Maya Powell
• 金额: $ 19.82万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-10 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10192909
• 关键词: Acetates; Affect; African; African American; Age; Anaerobic Bacteria; Bacteria; Bacterial Counts; Bacterial Vaginosis; Bioinformatics; Biological; Butyrates; Clinical; Clinical Trials Design; Cohort Studies; Communities; Data; Data Analyses; Discipline of obstetrics; Environment; Foundations; Genital; Genitalia; Goals; Gynecology; HIV; HIV Infections; HIV Seronegativity; HIV Seropositivity; HIV risk; Healthcare; Human; Inflammation; Inflammation Mediators; Inflammatory; Interdisciplinary Study; Interleukin-1 beta; Interleukin-6; Intervention; Lactic acid; Lactobacillus; Lactoferrin; Learning; Liquid substance; Measures; Mediating; Mentors; Metagenomics; Mucositis; Output; Pathway interactions; Patient Recruitments; Physicians; Population; Positioning Attribute; Pregnancy; Pregnancy Outcome; Pregnant Women; Premature Birth; Program Development; Propionates; Research; Research Design; Research Personnel; Resources; Risk; Role; Sampling; Scientist; Structure; Succinates; Techniques; Term Birth; Time; Training; Translating; Universities; Vagina; Viral; Viral Load result; Virus Shedding; Vision; Volatile Fatty Acids; Woman; Work; adverse pregnancy outcome; antileukoprotease; antimicrobial peptide; base; beta diversity; beta-Defensins; career; career development; cervicovaginal; chemokine; cohort; cytokine; design; dysbiosis; experience; experimental study; health care disparity; improved; indexing; inflammatory milieu; medical schools; metabolomics; microbiome; microbiome research; microbiota metabolites; perinatal HIV; pregnant; preventive intervention; professor; rRNA Genes; reproductive; skills; transmission process; vaginal microbiome; vaginal microbiota; vaginal mucosa

PROJECT SUMMARY/ABSTRACT This proposal presents a five year research career development program focused on the study of vaginal microbiome contributions to preterm birth among women with HIV to expand the breadth and depth of understanding of vaginal dysbiosis in preterm birth (PTB). The candidate is currently an Assistant Professor of Gynecology and Obstetrics at Johns Hopkins University School of Medicine. The outlined proposal builds on the candidate’s previous research and clinical experience in pregnancy outcomes among women with HIV and integrates two new domains of expertise of her mentors, Drs. Irina Burd and Khalil Ghanem at Johns Hopkins: inflammatory pathways leading to PTB with vaginal microbiome research. The proposed experiments and didactic work will position the candidate with a unique set of cross disciplinary skills that will enable her to transition to independence as a physician scientist with expertise in cohort study design and microbiome bioinformatics. Bacterial vaginosis (BV), an alteration in the vaginal microbiome, nearly doubles the risk of preterm birth, delivery prior to 37 weeks, and affects one third of women of reproductive age. In the US, women with HIV experience a two-fold increased risk of PTB compared to women without HIV. Women with HIV who have a Lactobacilus-deficient/ anaerobe-dominant vaginal microbiota have increased vaginal inflammation, higher genital HIV viral load and increased HIV viral shedding. The lacking data in US-based pregnant women with HIV risk perpetuating significant healthcare disparities. It is unknown whether the underlying mechanism between HIV infection and PTB is driven by vaginal dysbiosis. The foundation of this proposal is based on prior data documenting vaginal dysbiosis as a potential driver for altered inflammatory pathways and adverse pregnancy outcomes, particularly among African American women. Women with HIV and vaginal dysbiosis have increased risk for genital mucosa inflammation and viral shedding. The role of vaginal dysbiosis in pregnancy among women with HIV has not been explored to date, nor have the effects of ART on the vaginal microbiome in pregnancy. Specifically, this proposal aims to: 1) compare the structure (relative and absolute abundance) and composition (diversity) of the vaginal microbiota of pregnant women with HIV who experience PTB versus term birth, 2) determine the extent to which vaginal microbiota function, measured by median difference in metabolites (short chain fatty acids), correlates with PTB, and 3) measure and compare cervico- vaginal concentrations of soluble inflammatory mediators (antimicrobial peptides and pro-inflammatory cytokines) in PTB. The scientific objective of this proposal is to begin to define the strength of the association between vaginal microbiota, markers of mucosal inflammation and PTB among women with HIV and generate hypotheses that inform the direction and design of subsequent studies focused on potential interventions.

项目摘要/摘要 这项建议提出了一个五年的研究职业发展计划，重点是阴道的研究 微生物群对艾滋病毒感染妇女早产的贡献扩大其广度和深度 对早产(PTB)阴道生物失调的认识。该候选人目前是哈佛大学的助理教授。 约翰霍普金斯大学医学院妇产科。概述的提案建立在 候选人之前关于艾滋病毒携带者和女性妊娠结局的研究和临床经验 整合了她的导师、约翰·霍普金斯大学的伊琳娜·伯德博士和哈利勒·加尼姆博士的两个新的专业领域： 导致肺结核的炎症途径与阴道微生物组研究。建议的实验和 教学工作将使应聘者具备一套独特的跨学科技能，使她能够 转变为独立的内科科学家，在队列研究设计和微生物组方面拥有专业知识 生物信息学。 细菌性阴道病(BV)是一种阴道微生物群的改变，几乎使早产的风险增加一倍， 在37周之前分娩，影响到三分之一的育龄妇女。在美国，携带艾滋病毒的女性 与没有感染艾滋病毒的妇女相比，患肺结核的风险增加了两倍。感染艾滋病毒的妇女患有 乳杆菌缺乏/厌氧菌占优势的阴道微生物区系增加了阴道炎症， 生殖器艾滋病毒病毒载量和艾滋病毒病毒脱落率增加。缺乏数据的美国孕妇患有 艾滋病毒有可能使巨大的医疗差距永久化。目前尚不清楚潜在的机制是否 HIV感染和肺结核之间的关系是由阴道生物失调驱动的。这项提议的基础是以前的 记录阴道生物失调是炎症途径改变和不良反应的潜在驱动因素的数据 妊娠结局，特别是在非裔美国妇女中。患有艾滋病毒和阴道生物失调的妇女 会增加生殖器粘膜发炎和病毒脱落的风险。阴道菌群失调在妇科疾病中的作用 到目前为止，艾滋病毒携带者中的怀孕还没有被探索过，ART对阴道的影响也没有。 怀孕期间的微生物群。具体地说，这一建议旨在：1)比较结构(相对结构和绝对结构 HIV携带者孕妇阴道微生物区系的丰度和组成(多样性) PTB与足月分娩，2)确定阴道微生物区系功能的程度，通过中位数测量 与肺结核相关的代谢物(短链脂肪酸)的差异；3)测量和比较宫颈病变。 阴道中可溶性炎症介质(抗菌肽和促炎因子)的浓度 细胞因子)。这项提议的科学目标是开始确定协会的力量 女性HIV感染者阴道微生物区系、粘膜炎症标志物与肺结核之间的关系 为后续研究的方向和设计提供信息的假设侧重于潜在的干预措施。