The Vaginal Microbiome: Disease, Genetics and the Environment

阴道微生物组：疾病、遗传学和环境

• 批准号: 8313990
• 负责人: Gregory Allen Buck
• 金额: $ 191.21万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-15 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8313990
• 关键词: Address; Affect; African American; Age; Antibiotics; Area; Bacteria; Bacterial Vaginosis; Caucasians; Caucasoid Race; Chronic; Chronic Disease; Communicable Diseases; Data; Development; Diabetes Mellitus; Disease; Disease susceptibility; Dizygotic Twins; Environment; Environmental Exposure; Epithelial; Ethnic Origin; European; Evaluation; Future; Gastrointestinal tract structure; Genes; Genetic; Genital system; Genitourinary system; Genome; HIV-1; Hereditary Disease; Hispanics; Hormones; Human; Hysterectomy; Immunosuppressive Agents; Individual; Intervention; Knowledge; Laboratory Finding; Lead; Light; Maintenance; Menopause; Mexican; Microbe; Modeling; Molecular Analysis; Monozygotic Twinning; Monozygotic twins; Nucleic Acids; Oral cavity; Outcome; Pathologic; Personal Satisfaction; Physiological; Play; Population; Population Heterogeneity; Predisposition; Pregnancy; Pregnancy loss; Premature Birth; Process; Race; Registries; Relative (related person); Research; Risk; Role; Sampling; Second Pregnancy Trimester; Sexually Transmitted Diseases; Smoking; Surface; Technology; Testing; Twin Multiple Birth; Vagina; Vaginal Douching; Vaginitis; Virus Diseases; Woman; Women' s Health; base; disease transmission; instrument; microbial; microbiome; microorganism; pathogen; racial and ethnic; reproductive; research facility; transmission process

DESCRIPTION: The vagina is an interactive interface with the environment, and as such is covered by a protective epithelial surface. This surface, in turn, is colonized by bacteria and other microorganisms which, through a variety of mechanisms serve to further protect the host from invasion by pathogens. Alterations in the normal vaginal microflora, particularly those associated with bacterial vaginosis, are thought to contribute to risk of spontaneous pregnancy loss in the second trimester and spontaneous preterm birth. Additionally, alterations in the vaginal microbiome may increase the likelihood of transmission of certain agents including human immunodeficiency virus type 1 (HIV-1). There are physiologic alterations in host condition (e.g., menopause and pregnancy), which are beginning to be investigated as potential selective conditions for change in the "normal" flora, and their impact on disease susceptibility and transmission remains to be more definitively elucidated. The effects of chronically abnormal physiologic states (e.g., diabetes mellitus) on normal vaginal flora have not been well described or studied. Finally, an almost unexplored area of inquiry is the genetic contribution, including race/ethnicity, to the establishment and maintenance of a "normal" vaginal flora, under normal and physiologically altered circumstances. The proposed research will address gaps in our knowledge and shed light on how the vaginal microbiome contributes to adverse obstetrical outcomes and sexually transmitted disease in diverse populations. The aims of the project are intended to answer the following questions: Specific Aim 1. Do the genes of the host contribute to the composition of the vaginal microbiome? We hypothesize that a woman's genetic composition significantly affects the ability of certain commensal, parasitic and pathogenic microbes to colonize and/or infect the genital tract. This aim is divided into 2 subaims, the first of which will compare and quantify the microbial populations inhabiting the vaginas of monozygotic (MZ) and dizygotic (DZ) twins in the Mid Atlantic Twin Registry (MATR). The second subaim will address the question of whether there is a relationship between the microbiomes of the vagina, mouth and GI tract utilizing samples collected from the DZ and MZ twins. Specific Aim 2. What changes in the vaginal microbiome are associated with common physiological perturbations or non-infectious pathological states of the host? We hypothesize that "altered" physiologic (pregnancy, menopause) and pathologic (chronic disease, hysterectomy) conditions, or environmental "exposures" (exogenous hormones, antibiotics, chronic immunosuppressant, smoking; douching) can and often do predictably alter the vaginal microenvironment. These alterations in turn will lead to alterations in microbial populations within the vagina. Changes in the microbial populations may have impacts, positive or more likely negative, on the spontaneous and future well-being of the affected individual. We will characterize the effects of these "altered" physiologic and pathologic conditions, and environmental exposures exert on the composition of the vaginal microbiome, and test the hypothesis that they lead to predictable changes in the vaginal microbiome. The relationship between the molecular analysis of the microbiome and laboratory findings based on Amsel's criteria and the Nugent Score will be evaluated. Specific Aim 3. What changes in the vaginal microbiome are associated with relevant infectious diseases and conditions? We will test the hypothesis that infectious diseases predictably alter the vaginal microbiome, and that these changes have an impact on the disease process. We will also test the hypothesis that the vaginal microbiome has an impact on susceptibility to some relevant infectious diseases. The research to be conducted in this Specific Aim will provide a platform for modeling the impact of physiological, pathological, environmental and ethnic/racial factors, and their interactions, in determining the vaginal microbiome. In addition to providing critical descriptive data, this will be a hypothesis-generating Specific Aim. We will analyze the vaginal microbiomes of: normal women of reproductive age; women in the same age range with common pathological conditions (e.g., vaginosis, vaginitis, viral infections, bacterial STDs); women of three different ethnic/racial groups: European Caucasian, African-American, and Mexican Hispanic. We will address these questions using a combination of high throughput 'nextgen' sequencing technologies, including the Roche 454 FLX and the upgraded Illumina Genome Analyzer II instruments currently installed in the Nucleic Acids Research Facilities at VCU.

描述：阴道是与环境的交互界面，因此被保护性上皮表面覆盖。该表面反过来又被细菌和其他微生物定殖，这些微生物通过多种机制进一步保护宿主免受病原体的入侵。正常阴道菌群的改变，特别是与细菌性阴道病相关的菌群的改变，被认为会增加妊娠中期自发性流产和自发性早产的风险。此外，阴道微生物群的改变可能会增加某些病原体传播的可能性，包括 1 型人类免疫缺陷病毒 (HIV-1)。宿主状况（例如更年期和怀孕）存在生理变化，人们开始将其作为“正常”菌群变化的潜在选择性条件进行研究，并且它们对疾病易感性和传播的影响仍有待更明确地阐明。慢性异常生理状态（例如糖尿病）对正常阴道菌群的影响尚未得到充分描述或研究。最后，一个几乎未被探索的研究领域是在正常和生理改变的情况下，遗传因素（包括种族/民族）对“正常”阴道菌群的建立和维持的贡献。拟议的研究将弥补我们的知识空白，并揭示阴道微生物组如何导致不同人群的不良产科结果和性传播疾病。该项目的目的旨在回答以下问题： 具体目标 1. 宿主的基因是否有助于阴道微生物组的组成？我们假设女性的遗传组成显着影响某些共生微生物、寄生微生物和病原微生物定植和/或感染生殖道的能力。该目标分为 2 个子目标，第一个子目标将比较和量化中大西洋双胞胎登记处 (MATR) 中同卵 (MZ) 和异卵 (DZ) 双胞胎阴道中的微生物种群。第二个子目标将利用从 DZ 和 MZ 双胞胎收集的样本来解决阴道、口腔和胃肠道微生物组之间是否存在关系的问题。具体目标 2. 阴道微生物组的哪些变化与宿主常见的生理扰动或非感染性病理状态相关？我们假设“改变”的生理（怀孕、更年期）和病理（慢性疾病、子宫切除术）状况或环境“暴露”（外源性激素、抗生素、慢性免疫抑制剂、吸烟、冲洗）可以而且经常确实可预测地改变阴道微环境。这些改变反过来将导致阴道内微生物种群的改变。微生物种群的变化可能会对受影响个体的自发和未来福祉产生积极或更可能的消极影响。我们将描述这些“改变的”生理和病理条件以及环境暴露对阴道微生物组组成的影响，并检验它们导致阴道微生物组发生可预测变化的假设。将评估微生物组分子分析与基于 Amsel 标准和 Nugent 评分的实验室结果之间的关系。具体目标 3. 阴道微生物组的哪些变化与相关传染病和病症相关？我们将检验以下假设：传染病可预见地改变阴道微生物组，并且这些变化对疾病过程产生影响。我们还将检验阴道微生物组对某些相关传染病的易感性有影响的假设。在这一具体目标中进行的研究将为模拟生理、病理、环境和民族/种族因素及其相互作用在确定阴道微生物组方面的影响提供一个平台。除了提供关键的描述性数据之外，这还将是一个生成假设的具体目标。我们将分析以下人群的阴道微生物组： 正常育龄女性；具有常见病理状况的同年龄段女性（例如阴道病、阴道炎、病毒感染、细菌性性传播疾病）；三个不同民族/种族群体的女性：欧洲白种人、非洲裔美国人和墨西哥西班牙裔。我们将结合使用高通量“下一代”测序技术来解决这些问题，包括 Roche 454 FLX 和目前安装在 VCU 核酸研究设施中的升级版 Illumina Genome Analyzer II 仪器。

项目成果

The changing landscape of the vaginal microbiome.

• DOI: 10.1016/j.cll.2014.08.006
• 发表时间: 2014-12
• 期刊: Clinics in laboratory medicine
• 影响因子: 1.7
• 作者: Huang B;Fettweis JM;Brooks JP;Jefferson KK;Buck GA
• 通讯作者: Buck GA

BOTUX: bayesian-like operational taxonomic unit examiner.

BOTUX：类似贝叶斯的操作分类单元检查器。

• DOI: 10.1504/ijcbdd.2014.061652
• 发表时间: 2014
• 期刊: International journal of computational biology and drug design
• 作者: Koparde,VishalN;Adkins,RickyS;Fettweis,JenniferM;Serrano,MyrnaG;Buck,GregoryAA;Reimers,MarkA;Sheth,NiharU
• 通讯作者: Sheth,NiharU