A Multi'omics Approach towards Deciphering the Influence of the Microbiome on Pre

破译微生物组对预防的影响的多组学方法

• 批准号: 9091301
• 负责人: Kjersti Marie Aagaard
• 金额: $ 54.55万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-27 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9091301
• 关键词: Basal Plate; Biological Markers; Cataloging; Catalogs; Cells; Cervix Uteri; Child; Clinical; Clinical Research; Code; Collaborations; Common Good; Communities; Consent; DNA; DNA Sequence; Data; Development; Enrollment; Environment; Etiology; Feces; Fetal Membranes; Fetus; Funding; Future; Gene Expression; Generations; Genes; Genital system; Genitourinary system; Genome; Genomics; Gestational Age; Health; Hematogenous; Histocompatibility Antigens; Hominidae; Human; Human Genome; Human Microbiome; Immune; Infant; Infection; Inflammatory; Informatics; Institution; Integration Host Factors; Intervention; Lead; Learning; Medicine; Metabolic; Metadata; Metagenomics; Methods; Microbe; Molecular; Neonatal; Nurses; Oral; Organism; Perinatal; Periodontal Diseases; Physicians; Placenta; Population; Predisposition; Pregnancy; Pregnant Women; Premature Birth; Recording of previous events; Research; Research Proposals; Resources; Risk; Sampling; Science; Scientist; Second Pregnancy Trimester; Sepsis; Shotguns; Side; Site; Skin; Sterility; Structure; Taxon; Technology; Term Birth; Testing; Time; Umbilical Cord Blood; Umbilical cord structure; United States National Institutes of Health; Vagina; Whole-Genome Shotgun Sequencing; Woman; base; burden of illness; cohort; college; experience; fetal; genetic variant; gut microbiome; high throughput technology; innovation; intraamniotic infection; longitudinal design; metabolomics; metagenome; microbial; microbial community; microbial host; microbiome; microbiota; microorganism; oral microbiome; pathogen; postnatal; public health relevance; reconstruction; reproductive tract; residence; tool; transcriptome sequencing; transmission process; vaginal microbiome; whole genome

DESCRIPTION (provided by applicant): Humans are remarkable hosts to microbes, and we have in fact co-evolved as highly plethoric communities. Human-associated microorganisms (the "microbiome") are present in numbers exceeding the quantities of human cells by at least 10-fold beginning in the neonatal period The collective genome (the "metagenome") exceeds our human genome in terms of gene content by more than 150-fold. With respect to microbiota and preterm birth, it has generally assumed that the majority of intrauterine infections originate in the lower genital tract, with microbiota ascending into the otherwise sterile intrauterine environment to infect the placenta (preterm birth), fetal membranes (chorioamnionitis), umbilical cord (funisitis), and the fetus (sepsis). However, we and others have recently demonstrated that (1) the vaginal and gut microbiome communities are distinctly structured in pregnancy, and (2) the placenta is in fact not sterile, but rather harbors a low-abundance microbiome which is likely acquired through hematogenous transmission of the oral microbiome. Based on our prior studies and preliminary data, our central hypothesis is that a distinct and largely commensal resident microbiome in pregnancy renders risk for preterm birth. In order to prove this hypothesis, we will execute three essential aims: Aim 1 will use 16S-based approaches with inferred metagenomics employing samples from at-risk gravidae enrolled at <20 weeks gestation to reveal distinct microbial communities which occur in association with preterm birth; Aims 2&3 will use whole-genome shotgun sequencing with integrated host genomics, metatranscriptomics, and metabolomics to build on our functional computational pipelines and enable species identification, microbial gene catalogues, metabolic reconstructions, and mechanisms and networks of susceptibility to preterm birth. In addition, we describe our concomitant efforts to build a community resource for future large-scale studies on host and microbe biomarkers acquired in this set of preterm, near term, and term births. By utilizing our state-of-the-science technology and analysis tools in a longitudinal case-cohort of preterm birth subjects, we will be able to transform "discovery based" metagenomics and multi'omics science into readily translatable mechanistic studies at a previously unparalleled level. Our proven abilit to execute such clinical studies and utilize high-throughput technologies makes such large-scale "team science" feasible. Because preterm birth is prevalent in both the developed and developing world, these studies are of broad significance to our population's disease burden and will lead to potential innovative interventions.

描述（由申请人提供）：人类是微生物的非凡宿主，实际上我们已经作为高度庞大的社区共同发展。与人类相关的微生物（“微生物组”）以超过人类细胞数量的数量存在至少10倍，从新生儿时期开始，集体基因组（“元基因组”）超过了我们的人类基因组，其基因含量的含量超过150倍。关于菌群和早产，通常假设大多数子宫内感染起源于下生殖道，而微生物群升至原本无菌的子宫内环境中，以感染胎盘（早产），胎儿膜，胎儿膜（绒毛膜炎），柔术（umbilicalicalialical（funisis）（funisis）和fetus（fetus）和fetus（fetus）。但是，我们和其他人最近证明（1）阴道和肠道微生物组群落在怀孕中明显结构，并且（2）胎盘实际上不是无菌的，而是含有低丰度的微生物组，可能是通过血源性传播的血液传播而获得的。基于我们先前的研究和初步数据，我们的中心假设是，妊娠中的独特且在很大程度上是共同居民的微生物组，使早产风险。为了证明这一假设，我们将执行三个基本目标：AIM 1将使用16S基于推断的宏基因组学的方法采用少于20周的妊娠期妊娠的危险中的样本，以揭示与早产相关的不同微生物群落； AIM 2＆3将使用整体基因组shot弹枪测序与综合宿主基因组学，元文字组和代谢组学来建立我们的功能计算管道，并启用物种识别，微生物基因目录，代谢重建，机械机制，机械和网络，以使自早期生物的生育。此外，我们描述了我们为建立社区资源建立社区资源的努力，以在这套早产，近学期和定期出生中获得的关于宿主和微生物生物标志物的未来大规模研究。通过在纵向的早产学科中，利用我们的科学技术和分析工具，我们将能够将基于“发现的”元基因组学和多'词科学转换为以前无与伦比的水平。我们经过验证的执行此类临床研究并利用高通量技术使大规模的“团队科学”可行的事情可行。由于早产在发达国家和发展中国家都普遍存在，因此这些研究对我们人群的疾病负担具有广泛的意义，并将导致潜在的创新干预措施。