Vaginal Microbiome and Metabolites in Preterm Birth

早产中的阴道微生物组和代谢物

• 批准号: 10673751
• 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/10673751
• 关键词: Acetates; Affect; African; African American; Age; Anaerobic Bacteria; Bacteria; Bacterial Counts; Bacterial Vaginosis; Bioinformatics; Biological; Butyrates; Career Mobility; Clinical; Clinical Trials Design; Cohort Studies; Communities; Data; Data Analyses; Discipline of obstetrics; Disparity; Environment; Exclusion; Financial cost; Foundations; Genital; Genitalia; Goals; Gynecology; HIV; HIV Infections; HIV Seronegativity; HIV Seropositivity; HIV risk; Health Care Costs; Human; Inflammation; Inflammation Mediators; Inflammatory; Institution; 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 Load result; Virus Shedding; Vision; Volatile Fatty Acids; Woman; Work; adverse pregnancy outcome; antileukoprotease; antimicrobial peptide; beta diversity; beta-Defensins; career development; cervicovaginal; chemokine; cohort; cytokine; design; dysbiosis; experience; experimental study; health care disparity; improved; indexing; inflammatory milieu; medical schools; metabolomics; microbiome; microbiome research; perinatal HIV; pregnant; preventive intervention; professor; rRNA Genes; reproductive; skills; transmission process; vaginal fluid; 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.

项目总结/摘要 该提案提出了一项为期五年的研究职业发展计划，重点是研究阴道 微生物组对感染艾滋病毒妇女早产的贡献，以扩大 了解早产中的阴道微生态失调（PTB）。候选人目前是助理教授， 约翰霍普金斯大学医学院妇产科。概述的提案建立在 候选人以前在艾滋病毒感染妇女怀孕结果方面的研究和临床经验， 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PTB的炎症途径与阴道微生物组研究。所提出的实验和 教学工作将使候选人具有一套独特的跨学科技能，使她能够 过渡到独立的医生科学家，具有队列研究设计和微生物组方面的专业知识 生物信息学 细菌性阴道病（BV）是阴道微生物组的一种改变，几乎使早产的风险增加一倍， 怀孕37周之前分娩的妇女人数最多，三分之一的育龄妇女受到影响。在美国，感染艾滋病毒的女性 与未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， 乳酸杆菌缺陷/厌氧菌占主导地位的阴道微生物群增加了阴道炎症， 生殖器HIV病毒载量和HIV病毒脱落增加。缺乏美国孕妇的数据， 艾滋病毒有可能使重大的保健差距永久化。目前尚不清楚潜在的机制是否 HIV感染和PTB之间的关系是由阴道生态失调驱动的。这项建议的基础是基于先前的 记录阴道微生态失调作为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，特别是非洲裔美国妇女。感染艾滋病毒和阴道生态失调的妇女 增加生殖器粘膜炎症和病毒脱落的风险。阴道微生态失调在 到目前为止，艾滋病毒感染妇女怀孕的情况还没有得到研究，ART对阴道的影响也没有 怀孕期间的微生物具体而言，本建议旨在：1）比较结构（相对和绝对 感染HIV的孕妇的阴道微生物群的丰度）和组成（多样性）， PTB与足月分娩，2）确定阴道微生物群功能的程度，通过中位数测量 代谢物（短链脂肪酸）的差异，与PTB相关，以及3）测量和比较颈动脉- 可溶性炎症介质（抗微生物肽和促炎因子）的阴道浓度 细胞因子）。这项提议的科学目标是开始确定这种关联的强度 阴道微生物群，粘膜炎症标志物和PTB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。

项目成果

Experience and Outcomes of Breastfed Infants of Women Living With HIV in the United States: Findings From a Single-Center Breastfeeding Support Initiative.

美国艾滋病毒感染者母乳喂养婴儿的经验和结果：单中心母乳喂养支持计划的调查结果。

• DOI: 10.1093/jpids/piab116
• 发表时间: 2022
• 期刊: Journal of the Pediatric Infectious Diseases Society
• 影响因子: 3.2
• 作者: Yusuf,HasiyaE;Knott-Grasso,MaryAnn;Anderson,Jean;Livingston,Alison;Rosenblum,Nadine;Sturdivant,Heather;Byrnes,KristenC;Powell,Anna;Sheffield,JeanneS;Enns,Justine;Persaud,Deborah;Golden,WilliamChristopher;Agwu,AllisonL
• 通讯作者: Agwu,AllisonL

Structural Racism and Adverse Pregnancy Outcomes Through the Lens of the Maternal Microbiome.

• DOI: 10.1097/aog.0000000000005345
• 发表时间: 2023-10-01
• 期刊: Obstetrics and gynecology
• 影响因子: 7.2

Data on Safety of Intravaginal Boric Acid Use in Pregnant and Nonpregnant Women: A Narrative Review.

• DOI: 10.1097/olq.0000000000001562
• 发表时间: 2021-12-01
• 期刊: SEXUALLY TRANSMITTED DISEASES
• 影响因子: 3.1
• 作者: Mittelstaedt, Rachel;Kretz, Alyssa;Levine, Michael;Handa, Victoria L.;Ghanem, Khalil G.;Sobel, Jack D.;Powell, Anna;Tuddenham, Susan
• 通讯作者: Tuddenham, Susan