Longitudinal investigations of the infant virome and its associations with obesity

婴儿病毒组的纵向研究及其与肥胖的关系

• 批准号: 9564164
• 负责人: Julie Parsonnet
• 金额: $ 55.21万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-12 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9564164
• 关键词: 3 year old; Acute; Adult; Affect; Age; Animals; Area; B-Lymphocytes; Bangladesh; Bangladeshi; Bioinformatics; Birth; Birth Weight; Blood; Body Fluids; California; Characteristics; Child; Childbirth; Childhood; Chronic; Clinical; Collection; Communicable Diseases; Computing Methodologies; Coupled; Data; Databases; Development; Endocrine; Epidemiology; Feces; Fever; Frequencies; Gastroenteritis; Growth; Growth and Development function; Hormones; Household; Human; Human Microbiome; Immune; Immunity; Incidence; Infant; Infection; Investigation; Life; Longitudinal Studies; Longitudinal cohort; Measures; Metabolic; Metabolic Marker; Metagenomics; Molecular Biology; Neurologic; Nose; Obesity; Outcome; Pathogenesis; Pathogenicity; Pathway Analysis; Population; Prevention; Protocols documentation; Role; Saliva; Sampling; Serum; Severities; Site; Statistical Methods; Swab; System; T-Lymphocyte; Time; Uterus; Viral; Viral Load result; Virus; Virus Diseases; Weight Gain; Work; bacteriome; cohort; comparison group; cytokine; early childhood; gastrointestinal; host-microbe interactions; inflammatory marker; innovation; metagenome; microbial; microbiome; neonate; news; next generation sequencing; novel; obesity in children; respiratory; statistics; tool; virome

PROJECT SUMMARY The role of the human microbiome in growth and development has become an intensive area of investigation and convincing data demonstrate that perturbations can influence growth in adults and in animals. Almost all work, however, has focused on the bacterial microbiome, and not on the even more abundant eukaryotic and prokaryotic virome. The virome, however, has equal or more potential to affect growth. In children under three years old, the great majority of infections are caused by viruses; these infections take both a metabolic toll and, on a more chronic level, have the potential to highjack endocrine, neurologic and metabolic systems. To date, however, very little is known about this essential component of the human metagenome. Prior studies on the virome: 1) have been limited as to body site investigated, 2) have not typically included healthy children, and 3) do not capture the dynamic changes in the virome occurring over time. Here we propose to use metagenomic next-generation sequencing (NGS) to analyze the gut, respiratory, and blood virome in serially collected samples from 86 children from birth to age 3, collected as part of a unique, multiethnic, pediatric cohort from northern California (the STORK study). A comparison group of 50 Bangladeshi children will also be assessed. Longitudinal sampling of the pediatric virome will reveal how the virome is initially established and changes over time. We hypothesize that establishment of a baseline virome and dynamic changes from birth to three years will have a significant impact in modulating growth in young children. Novel aspects of this project include: (1) longitudinal sampling of child from birth to age 3 years in the US, (2) simultaneous sampling of the virome in three body fluid compartments (blood, nasal swabs, and stool), (3) state-of-the-art metagenomic analysis by NGS coupled to a rapid bioinformatics pipeline, (4) accurate viral quantitation using a massively parallel NGS multiplexing approach and (5) ability to correlate viral findings with well-curated anthropometric, clinical and epidemiological outcomes data to search for associations, and with immunome and microbiome data generated in other projects to enable network analysis of host-microbial interactions. The proposed project will generate the most comprehensive and in-depth analysis to date of how the virome impacts growth in early life and has the potential to alter our approach to pathogenesis, prevention and treatment of childhood obesity.

项目摘要 人类微生物组在增长和发展中的作用已成为 调查和令人信服的数据表明，扰动会影响成人和动物的生长。 但是，几乎所有工作都集中在细菌微生物组上，而不是更丰富的 真核生物和原核生物病毒蛋白。但是，病毒蛋白具有影响生长的相等或更多潜力。在 三岁以下的儿童，绝大多数感染是由病毒引起的。这些感染两者都 代谢性死亡人数，在更慢性的水平上，有可能进行高砍可内分泌，神经系统和 代谢系统。然而，迄今为止，对人类的这一重要组成部分知之甚少 元基因组。先前对病毒蛋白的研究：1）在研究身体部位的情况下受到限制，2）尚未 通常包括健康的孩子，3）请勿捕获病毒蛋白发生的动态变化 时间。在这里，我们建议使用宏基因组下一代测序（NGS）来分析肠道，呼吸系统 从出生到3岁的86名儿童的串行收集样本中的血液病毒蛋白，作为A的一部分 来自北加州的独特，多种族的儿科队列（Stork研究）。 50的比较组 孟加拉国儿童也将进行评估。小儿病毒蛋白的纵向采样将揭示 Virome最初是建立的，并且会随着时间的推移而变化。我们假设建立基线病毒蛋白 从出生到三年的动态变化将对调节年轻人的增长产生重大影响 孩子们。该项目的新颖方面包括：（1）从出生到3岁的孩子的纵向采样 美国（2）在三个体液室（血液，鼻拭子和凳子）中同时对病毒素进行采样， （3）NGS与快速生物信息学管道相结合的NGS的最先进的元基因组分析，（4）精确病毒 使用大规模并行NGS多路复用方法进行定量，（5）将病毒发现与 经过良好策划的人体测量学，临床和流行病学结果数据以搜索关联，并与 在其他项目中生成的免疫组和微生物组数据，以实现宿主微生物的网络分析 互动。拟议的项目将生成迄今为止最全面，最深入的分析 病毒蛋白会影响早期生命的生长，并有可能改变我们的发病机理方法 和儿童肥胖症的治疗。