Dysbiosis, Recurrent Bacterial Vaginosis and the Vaginal Microbiome

菌群失调、复发性细菌性阴道病和阴道微生物组

• 批准号: 9297211
• 负责人: Susan Anne Tuddenham
• 金额: $ 19.7万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9297211
• 关键词: Affect; Amination; Amines; Amino Acids; Anaerobic Bacteria; Antibiotic Therapy; Bacteria; Bacterial Counts; Bacterial Vaginosis; Biogenic Amines; Characteristics; Clinical; Clinical Investigator; Clinical Medicine; Clinical Research; Cluster Analysis; Cohort Studies; Communities; Complex; Consensus; Data; Data Analyses; Databases; Development; Disease; Epithelial Cells; Funding; Gardnerella; Genitourinary System Infection; Genitourinary system; Glycogen; Goals; HIV; Health; Hemorrhage; Infection; Intervention; Isomerism; Knowledge; Lactic acid; Lactobacillus; Lead; Leptotrichia; Link; Longitudinal Studies; Measures; Mentorship; Metagenomics; Microbial Biofilms; Molecular; Mucins; Mucous body substance; Observational Study; Organism; Outcome; Output; Pathogenesis; Pathogenicity; Patient Recruitments; Patients; Predisposition; Premature Labor; Prevotella; Production; Recruitment Activity; Recurrence; Reproductive Health; Risk; Sexual Transmission; Sexually Transmitted Diseases; Structure; Symptoms; Syndrome; Techniques; Training; United States National Institutes of Health; Vagina; Woman; Work; base; cohort; data management; design; epidemiology study; experience; hormonal contraception; improved; insight; metabolome; metabolomics; microbial community; microbiome; microbiota; multilevel analysis; prevent; rRNA Genes; reproductive; skills; targeted treatment; tool; transmission process; vaginal microbiome

Project Summary/Abstract: Disrupted or “dysbiotic” vaginal microbiota, as epitomized by the clinical syndrome of bacterial vaginosis (BV), can result in severe recurrent symptoms despite antibiotic therapy, as well as serious reproductive consequences including preterm labor and the acquisition and transmission of sexually transmitted infections. New molecular techniques are enabling a more sophisticated understanding of the complex structure of vaginal microbial communities, while studies from the nascent field of metabolomics suggest that the functional output of these microbiota may be a key factor in the pathogenesis of dysbiosis. Hormonal contraception (HC) has been shown in epidemiologic studies to decrease the risk of incident and recurrent BV in some, but not all women. Preliminary data suggests that HC stabilizes and shifts the microbiota away from the low-lactobacilli, mixed anaerobe-predominant communities characteristic of BV. As such, it may hold promise as a way to ameliorate dysbiosis and treat recurrent BV in selected patients. However, despite over 50 years of widespread use, our understanding of the impact of HC on the structure of vaginal communities in asymptomatic women is incomplete, and the impact of HC on the function of vaginal communities in these women is not known. Additionally, the impact of HC on the structure and function of the vaginal microbiota in women with recurrent BV is unknown. This proposal seeks to elucidate these questions through 3 aims: 1) To evaluate the impact of HC on the structure of the vaginal microbiota in asymptomatic women as measured by absolute bacterial counts of Lactobacillus species, (in particular L. iners), and other selected anaerobes in vaginal microbial communities, 2) To determine the impact of HC on the function of the vaginal microbiota in asymptomatic women as measured by the production of lactic acid isomers and biogenic amines, and 3) To evaluate the impact of HC on the structure and function of the vaginal microbiota in a small pilot cohort of women with recurrent BV. Aims 1 and 2 will be nested within an existing cohort study, the Hormonal Contraception Longitudinal Study. For aim 3, the PI will recruit a small pilot cohort for an observational study of women with recurrent BV starting on HC. Through formal didactics and structured mentorship from a team which comprises experts in genitourinary infections, metagenomics, and advanced analytics, the PI will develop a unique analytic skill set, including knowledge of the R statistical package, longitudinal data analysis, multi-level modeling, principle component analysis and hierarchical clustering analysis, as well as experience in patient recruitment and clinical research. This will enable her to achieve the long-term goal of becoming an independent clinical investigator who will utilize the powerful new tools of metagenomics and metabolomics to design and lead interventions to improve clinical outcomes in women.

项目概要/摘要： 细菌性阴道病（BV）临床综合征是阴道微生物群失调或"生态失调"的缩影， 尽管进行了抗生素治疗，但仍可能导致严重的复发症状， 后果包括早产和性传播感染的获得和传播。 新的分子技术使人们能够更复杂地理解 阴道微生物群落，而来自代谢组学新兴领域的研究表明， 这些微生物群的输出可能是生态失调发病机制中的关键因素。激素避孕（HC） 流行病学研究显示，在某些（但不是全部）患者中， 妇女初步数据表明，HC稳定并使微生物群远离低乳酸杆菌， BV的混合厌氧菌优势群落特征。因此，它可能有希望作为一种方式， 在选定的患者中改善生态失调和治疗复发性BV。尽管50多年来 广泛使用，我们了解HC对阴道群落结构的影响， 无症状妇女是不完整的，HC对这些妇女阴道群落功能的影响是不完整的。 女人不知道。此外，HC对阴道微生物群的结构和功能的影响也是不确定的。 复发性BV的女性不详。这项建议旨在透过三个目的澄清这些问题： 评价HC对无症状女性阴道微生物群结构的影响， 乳杆菌属物种（特别是L. iners）和其他选定的厌氧菌， 阴道微生物群落，2）确定HC对阴道微生物群功能的影响， 通过乳酸异构体和生物胺的产生来测量的无症状妇女，和3） 在一个小型试验性队列中评估HC对阴道微生物群结构和功能的影响， 复发性BV的女性。目标1和2将嵌套在现有的队列研究中，激素 避孕纵向研究。对于目标3，PI将招募一个小型试点队列进行以下观察性研究： 从HC开始的复发性BV女性。通过正式的教学法和来自团队的结构化指导 由泌尿生殖感染、宏基因组学和高级分析专家组成，PI将 发展独特的分析技能，包括R统计软件包的知识，纵向数据分析， 多层次建模、主成分分析和层次聚类分析，以及经验 病人招募和临床研究这将使她能够实现成为一名 独立的临床研究者，他们将利用宏基因组学和代谢组学的强大新工具， 设计和领导干预措施，以改善妇女的临床结果。