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 该建议提出了一项五年研究职业发展计划，重点是阴道研究 微生物组对艾滋病毒女性早产的贡献，以扩大 对早产（PTB）中阴道营养不良的了解。候选人目前是 约翰·霍普金斯大学医学院的妇科和妇产科。概述的提案以 候选人以前在艾滋病毒和艾滋病毒妇女中在怀孕结局方面的研究和临床经验 整合了她的导师博士的两个新专业知识领域。约翰·霍普金斯（Johns Hopkins）的艾琳娜·伯德（Irina Burd）和哈利尔·加纳姆（Khalil Ghanem）： 通过阴道微生物组研究导致PTB的炎症途径。提出的实验和 教学工作将为候选人提供独特的跨学科技能，使她能够 过渡到具有队列研究设计专业知识和微生物组专业知识的物理科学家到独立性 生物信息学。 细菌性阴道化（BV）是阴道微生物组的改变，几乎使早产的风险翻了一番 在37周之前分娩，并影响生殖年龄的三分之一。在美国，艾滋病毒的妇女 与没有艾滋病毒的女性相比，PTB风险增加了两倍。患有艾滋病毒的妇女 缺乏乳杆菌/厌氧症的阴道菌群增加了阴道注射，更高 生殖器HIV病毒载量和HIV病毒脱落的增加。美国的孕妇缺乏数据 艾滋病毒风险延续了大量医疗保健分布。尚不清楚基本机制是否 在HIV感染和PTB之间是由阴道营养不良驱动的。该提议的基础是基于先验 记录阴道营养不良的数据是改变炎症途径和逆境的潜在驱动因素 怀孕结果，特别是在非裔美国妇女中。艾滋病毒和阴道营养不良的妇女 生殖器粘膜感染和病毒脱落的风险增加。阴道营养不良中的作用 迄今为止尚未探讨艾滋病毒女性的怀孕，艺术对阴道的影响也没有 怀孕的微生物组。具体而言，该建议的目的是：1）比较结构（相对和绝对 艾滋病毒孕妇的阴道微生物群的丰度）和经历的孕妇的成分（多样性） PTB与期限出生，2）确定通过中位数测量的阴道菌群功能的程度 代谢物（短链脂肪酸）的差异，与PTB相关，3）测量并比较子宫颈 固体炎症介质的阴道浓度（抗菌胡椒和促炎 PTB中的细胞因子）。该提议的科学目标是开始定义关联的力量 在阴道微生物群之间，艾滋病毒女性的粘膜注射和PTB标记和PTB 假设为随后研究的方向和设计提供了侧重于潜在干预措施的方向和设计。