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THE VAGINAL MICROBIOME, MATERNAL RESPONSE, AND PRETERM BIRTH

阴道微生物组、孕产妇反应和早产

基本信息

批准号：
9578621
负责人：
Molly Stout
金额：
$ 65.36万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-12 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9578621
关键词：
37 weeks gestation Anti-inflammatory Bacteria Bacterial Genes Base Sequence Biological Biology Chickenpox Clinical Clinical Data Communities Data Decision Trees Development Disease Distant Environment Epidemiologist Family Future Gene Expression Genome Genomics Goals Health Care Costs Human Papillomavirus Immune response Infant Infection Inflammation Inflammatory Inflammatory Response Influenza Informatics Institutes Investigation Joints Knowledge Lead Life Light Link Malignant neoplasm of cervix uteri Measurable Metagenomics Microbe Morbidity - disease rate Neonatal Mortality Outcome Pathway interactions Patients Physiological Pregnancy Pregnancy Complications Pregnant Women Premature Birth Prevention Prevention Measures Prevention strategy Production Public Health Research Research Design Research Infrastructure Ribosomal RNA Risk Sampling Screening procedure Shotgun Sequencing Signal Transduction Specimen Structure Survivors Technology Term Birth Testing Time United States Universities Vagina Viral Virus Virus Diseases Washington Woman bacterial community bacteriome clinical application cohort cost cytokine design genome sequencing high risk improved innovation microbial microbial community microbial host microbiome mortality neonatal morbidity novel patient population predictive signature prevent racial diversity response vaginal microbiome virome

项目摘要

ABSTRACT An estimated 13 million preterm births (PTBs) occur annually worldwide, and PTB is the single most significant contributing factor to neonatal morbidity and mortality. Mechanisms underlying preterm birth are unknown hampering development of effective prediction and prevention strategies. PTB is linked to local and distant infections and recent data suggests that vaginal bacterial microbiome early in pregnancy is associated with subsequent preterm birth. Viral infections behave differently during pregnancy, with common viral infections such as varicella and influenza causing much more severe disease during pregnancy and human papillomavirus, the causative virus in cervical cancer, associated with a 2-fold increased risk for PTB. However, comprehensive assessment of vaginal viral communities during pregnancy has not been performed. Lastly, although maternal inflammation is one of the leading triggers for PTB the precise constellation of inflammatory signals is not known. We propose that examining microbial communities or host response alone is incomplete, but that their combination will lead to refined definitions of appropriate and inappropriate microbe-maternal biology and shed new light on the old problem of PTB. Our central hypothesis is that preterm birth can be estimated by a combination of three criteria: vaginal bacterial communities, vaginal eukaryotic viral communities, and maternal inflammatory response. We have an interdisciplinary team assembled including perinatologists, epidemiologists, virologists, and genomics informatics experts, leveraging the unique capabilities of the McDonnell Genome Institute at Washington University in St. Louis, a well-established pregnancy bio-specimen and clinical data infrastructure, and a high-PTB burdened racially diverse patient population to test this novel hypothesis. The aims of this project are: 1) Determine the ability of bacterial and viral communities in the vagina and their dynamics over time to predict preterm birth 2) Determine the ability of the host inflammatory response in the vagina in the context of microbial communities to predict preterm birth. The proposed research is innovative, for the first time, comprehensively characterizing the eukaryotic vaginal virome simultaneously with vaginal bacterial communities and longitudinally capturing the maternal response to these communities. We employ an efficient study design, a well-established research infrastructure, and renowned genome sequencing expertise to test a physiologically plausible but uninvestigated paradigm that bacterial and viral communities in concert with the maternal host response can predict PTB.

摘要