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: 9163096
• 负责人: Susan Anne Tuddenham
• 金额: $ 18.42万
• 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/9163096
• 关键词: Affect; 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; Epidemiologic Studies; Epithelial Cells; Funding; Gardnerella; Genitourinary System Infection; Genitourinary system; Glycogen; Goals; HIV; Health; Hemorrhage; Infection; Intervention; Isomerism; Knowledge; Lactic acid; Lactobacillus; Lead; Leptothrix; Leptotrichia; Link; Longitudinal Studies; Measures; Mentorship; Metagenomics; Microbial Biofilms; Modeling; Molecular; Mucins; Mucous body substance; Observational Study; Organism; Outcome; Output; Pathogenesis; Patient Recruitments; Patients; Predisposition; Premature Labor; Prevotella; Production; Recruitment Activity; Recurrence; Reproductive Health; Risk; Sexually Transmitted Diseases; Structure; Symptoms; Syndrome; Techniques; Training; United States National Institutes of Health; Vagina; Woman; Work; abstracting; base; cohort; data management; design; experience; hormonal contraception; improved; insight; metabolome; metabolomics; microbial community; microbiome; microbiota; 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.

项目摘要/摘要： 阴道微生物群被破坏或“失调”，以细菌性阴道病 (BV) 临床综合征为代表， 尽管接受抗生素治疗，仍可能导致严重的复发症状以及严重的生殖问题 后果包括早产以及性传播感染的获得和传播。 新的分子技术使人们能够更深入地理解复杂的结构 阴道微生物群落，而代谢组学新兴领域的研究表明，功能性 这些微生物群的输出可能是激素避孕（HC）发病机制的关键因素。 流行病学研究表明，可降低某些人（但并非全部）发生 BV 事件和复发的风险 初步数据表明，HC 可以稳定微生物群并将其从低乳酸菌中转移出来。 BV 的混合厌氧菌为主的群落特征因此，它可能有望作为一种方法。 改善生态失调并治疗选定患者的复发性 BV 然而，尽管已有 50 多年的历史。 广泛使用，我们了解 HC 对阴道群落结构的影响 无症状女性的研究是不完整的，HC 对这些女性阴道群落功能的影响 此外，HC 对阴道微生物群结构和功能的影响尚不清楚。 患有复发性 BV 的女性尚不清楚。该提案旨在通过 3 个目标来阐明这些问题：1) 评估 HC 对无症状女性阴道微生物群结构的影响，测量方法为 乳杆菌（特别是惰性乳杆菌）和其他选定厌氧菌的绝对细菌计数 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衡量的无症状女性，以及 3) 在一个小型试点队列中评估 HC 对阴道微生物群结构和功能的影响 目标 1 和 2 的女性复发性 BV 将纳入现有的队列研究“激素”中。 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观察性研究。 通过正式的教学和团队的结构化指导，患有复发性 BV 的女性开始接受 HC。 该 PI 由泌尿生殖感染、宏基因组学和高级分析方面的专家组成， 开发一套独特的分析技能，包括 R 统计包知识、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 这将使她能够实现成为一名患者的长期目标。 独立的临床研究者将利用宏基因组学和代谢组学的强大新工具来 设计和领导干预措施以改善女性的临床结果。