Quantifying the interactions among maternal race, vaginal metabolites, and microbes in preterm birth

量化早产中母体种族、阴道代谢物和微生物之间的相互作用

• 批准号: 10860924
• 负责人: William Francis Kindschuh
• 金额: $ 4.87万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-15 至 2026-09-14
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10860924
• 关键词: 16S ribosomal RNA sequencing; 37 weeks gestation; Address; Affect; Biological Markers; Birth; Black race; Clinical; Clinical Data; Computational Biology; Data; Data Analyses; Early Diagnosis; Elements; Environmental Risk Factor; Foundations; Future; Genomics; Growth; Intervention; Investigation; Maternal complication; Measures; Medical; Metabolic; Metabolism; Metadata; Metagenomics; Microbe; Mothers; Neonatal Mortality; Nulliparity; Participant; Population; Population Heterogeneity; Pregnancy; Pregnancy Rate; Pregnant Women; Premature Birth; Prevention; Race; Reproductive Biology; Reproductive Health; Research; Resolution; Risk Factors; Role; Sample Size; Sampling; Second Pregnancy Trimester; Statistical Methods; Swab; Time; Tyramine; United States; Vagina; Virulence; Woman; Work; biomarker identification; black women; cohort; data modeling; disability; genetic element; high risk; improved; innovation; insight; machine learning model; maternal morbidity; mathematical model; metabolome; metabolomics; metagenomic sequencing; microbial; microbial products; microbiome; microbiome composition; microorganism interaction; mortality; neonatal morbidity; neonate; novel; potential biomarker; prevent; racial disparity; racial diversity; social; social factors; socioeconomics; vaginal microbiome

Project Summary/Abstract Despite years of investigation into its causes and potential biomarkers, the rate of pregnancies ending preterm in the United States has remained around 10% in the overall population and 15% in Black women. Two thirds of preterm births occur spontaneously and are not initiated by a medical intervention. As spontaneous preterm birth is a leading cause of neonatal morbidity and mortality, and is associated with maternal complications, it both reflects and drives significant racial disparities in reproductive health. We and others have shown that both vaginal metabolites and microbes are associated with spontaneous preterm birth, but also that these associations vary across races. Therefore, in order to identify biomarkers that will enable early diagnosis of preterm birth and develop strategies for its prevention in diverse populations, we must fully understand how maternal race interacts with these associations. Understanding the role of race in spontaneous preterm birth will require identifying the social and environmental variables that explain its impact on microbial and metabolite risk factors. Previous studies on the influence of race on the associations between vaginal metabolites, microbes, and preterm birth suffered from small sample sizes, limited clinical data, and a lack of longitudinal data. They also relied on 16S rRNA gene sequencing, which measures only the composition of the microbiome, and does not account for strain differences or quantify functional genetic elements. The objective of this proposal is to study the interactions among maternal race, vaginal metabolite levels, vaginal microbes, and spontaneous preterm birth. I will perform a paired analysis of vaginal metabolites and vaginal metagenomic sequencing data, which profiles the entire genomic content of the microbiome. The data I will analyze originates from the nuMoM2b cohort, a large, extensively characterized, and racially-diverse cohort of pregnant women, in which microbiome samples were collected at multiple timepoints. My central hypothesis is that maternal race has significant interactions with the associations among vaginal metabolites, vaginal microbes, and preterm birth. To understand these interactions, I will identify associations between vaginal metabolites and functional elements of vaginal microbes with spontaneous preterm birth, and compare them between Black and white women. I will also identify microbiome dynamics using longitudinal data and mathematical models of microbial interactions and growth rates. I will then identify the social and environmental factors that explain the influence of race on associations among vaginal microbes, metabolites, and preterm birth. This project will identify preterm birth risk factors that will be useful in diverse populations, will raise additional hypotheses regarding potential mechanisms underlying spontaneous preterm birth in both Black and white women, and will lay a groundwork for future research on preterm birth treatment and prevention.

项目概要/摘要 尽管对其原因和潜在的生物标志物进行了多年的调查，但早产终止率 在美国，黑人女性的比例一直保持在总人口的 10% 左右，黑人女性的比例则保持在 15% 左右。三分之二的 早产是自发发生的，并非由医疗干预引发。作为自发性早产 是新生儿发病和死亡的主要原因，并且与孕产妇并发症相关，它既 反映并推动了生殖健康方面的显着种族差异。我们和其他人已经证明， 阴道代谢物和微生物与自发性早产有关，而且这些 协会因种族而异。因此，为了识别能够早期诊断的生物标志物 早产并制定不同人群的预防策略，我们必须充分了解如何 母系种族与这些关联相互作用。了解种族在自发性早产中的作用将 需要确定社会和环境变量来解释其对微生物和代谢物风险的影响 因素。先前关于种族对阴道代谢物、微生物、 早产的样本量小、临床数据有限且缺乏纵向数据。他们 还依赖于 16S rRNA 基因测序，该测序仅测量微生物组的组成，并且 不考虑菌株差异或量化功能遗传元件。 该提案的目的是研究母亲种族、阴道代谢物水平、阴道 微生物和自发性早产。我将对阴道代谢物和阴道分泌物进行配对分析 宏基因组测序数据，描述微生物组的整个基因组内容。我要的数据 分析源自 nuMoM2b 队列，这是一个大型、广泛特征且种族多样化的队列 孕妇，在多个时间点收集微生物组样本。我的中心假设是 母体种族与阴道代谢物、阴道 微生物和早产。为了理解这些相互作用，我将确定阴道之间的关联 自发性早产阴道微生物代谢物及功能成分分析及比较 黑人和白人妇女之间。我还将使用纵向数据和 微生物相互作用和生长速率的数学模型。然后我将确定社会和环境 解释种族对阴道微生物、代谢物和早产之间关联的影响的因素 出生。该项目将确定对不同人群有用的早产风险因素，将提高 关于黑人和黑人自发性早产潜在机制的其他假设 白人女性，将为未来早产治疗和预防的研究奠定基础。