Longitudinal investigations of the infant virome and its associations with obesity

项目摘要 人类微生物组在生长和发育中的作用已成为研究的重点领域。 调查和令人信服的数据表明，扰动可以影响成年人和动物的生长。 然而，几乎所有的工作都集中在细菌微生物组上，而不是更丰富的微生物组。 真核和原核病毒组。然而，病毒组具有同等或更大的影响生长的潜力。在 对于三岁以下的儿童来说，绝大多数感染是由病毒引起的;这些感染既包括 代谢的代价，并在更长期的水平上，有可能劫持内分泌，神经系统和 代谢系统然而，迄今为止，对人体的这一重要组成部分所知甚少。 宏基因组先前对病毒组的研究：1）限于研究的身体部位，2）没有 通常包括健康儿童，和3）不捕获病毒组中发生的动态变化， 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，呼吸道， 从86名从出生到3岁的儿童中连续收集的样本中，血液病毒组和血液病毒组， 来自北方加州的独特的多种族儿科队列研究（STORK研究）。50人的对照组 孟加拉国儿童也将接受评估。儿科病毒组的纵向取样将揭示 病毒组最初建立并随时间变化。我们假设基线病毒组的建立 从出生到三岁的动态变化将对调节年轻人的生长产生重大影响。 孩子该项目的创新之处包括：（1）对儿童从出生到3岁的纵向抽样， US，（2）在三个体液隔室（血液、鼻拭子和粪便）中同时采样病毒组， (3)通过NGS结合快速生物信息学管道进行最先进的宏基因组分析，（4）准确的病毒 使用大规模并行NGS多重方法进行定量和（5）将病毒发现与 精心策划的人体测量，临床和流行病学结果数据，以寻找相关性， 在其他项目中生成的免疫组和微生物组数据， 交互.拟议的项目将产生迄今为止最全面和深入的分析， 病毒组影响生命早期的生长，并有可能改变我们对发病机制、预防 和儿童肥胖症的治疗。

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.