Longitudinal Study of the Small Intestine Bacterial Overgrowth Microbiome and Its Effect on Growth and Neurodevelopment in Malnourished Children

项目总结 候选人：我是弗吉尼亚联邦大学的儿科传染病助理教授 (VCU)，它有一所研究密集型医学院。我曾在我的导师Dr。 威廉·佩里写了4年，出版了10本书，其中4本是第一作者。我已经在最近的3个年度 美国热带医学和卫生学会的会议，并已从 VCU儿童医院基金会、比尔和梅林达·盖茨基金会以及Pantheryx，Inc. 职业发展计划/职业目标和目标：我的目标是成为一名独立资助的 在设计和进行试验方面具有专业知识的临床研究人员，以了解和缓解 低收入环境下传染病对儿童健康的影响。为此，我将采取几个 临床研究设计与实施课程。我有一个成功资助的顾问委员会 与我有相似兴趣的研究人员，他们在指导年轻科学家方面有良好的记录。 研究计划：这项K23奖项中提议的工作将利用两项现有的队列研究进行 目前正在由我的导师佩里博士和我们在孟加拉国的合作者进行。 具体目标1：测试婴儿时期GHBT阳性是否预示着未来的发育迟缓和 孟加拉儿童的神经发育缺陷。计划：使用持续的出生队列，我将测量 在生命的头两年的四个时间点进行GHBT，并测试与人体测量结果的相关性 和贝利婴幼儿发展量表。 具体目标2：确定与GHBT相关的十二指肠微生物组的结构和功能。 此外，检测GHBT阳性的十二指肠微生物群与粪便微生物群是否相关 婴儿。计划：我们将对来自孟加拉国的十二指肠和粪便样本进行16S rDNA V4测序 有和没有GHBT阳性的儿童。在一个子集中，我们还将执行元基因组测序 研究这种生物失调如何影响肠道微生物群的代谢功能，重点是氢 生产和消费。 导师/共同导师(S)，合作者(S)：这款K23的主要导师威廉·佩里博士有30年的经验 美国国立卫生研究院的资助记录和出色的指导。我的顾问委员会和合作者包括 微生物组研究、肠道病原体、营养不良、环境肠病和儿科调查。 环境和机构对候选人的承诺：我可以在VCU获得极好的资源， 弗吉尼亚大学和孟加拉国国际腹泻病研究中心。我有一个 我的部门和部门的坚定承诺，确保75%受保护的研究时间和支持我的 继续在弗吉尼亚大学佩里博士的指导下工作。此外，VCU的研究主任 医学院是我的顾问委员会成员，展示了非凡的机构支持。

PROJECT SUMMARY Candidate: I am Assistant Professor of Pediatric Infectious Diseases at Virginia Commonwealth University (VCU), which has a research-intensive school of medicine. I have conducted research under my mentor Dr. William Petri for 4 years and have 10 publications, 4 as first author. I have presented at the last 3 annual meetings of the American Society of Tropical Medicine and Hygiene and have secured research funding from the VCU Children's Hospital Foundation, the Bill and Melinda Gates Foundation, and Pantheryx, Inc. Career Development Plan/Career Goals & Objectives: It is my goal to become an independently funded clinical researcher with expertise in designing and conducting trials to understand and mitigate the effect of infectious diseases on child health in low-income settings. To this end, I will take several classes in clinical research design and implementation. I have an advisory committee of successfully funded researchers with similar interests to my own that have proven track records in mentoring young scientists. Research Plan: The work proposed in this K23 award will take place utilizing two existing cohort studies currently being conducted by my mentor, Dr. Petri, and our collaborators in Bangladesh. Specific Aim 1: Test if a positive GHBT in infancy is predictive of future stunting and neurodevelopmental deficits in Bangladeshi children. Plan: Using an ongoing birth cohort, I will measure GHBT at four time points in the first two years of life and test for an association with anthropometric outcomes and the Bayley Scales of Infant and Toddler Development. Specific Aim 2: Define the structure and function of the duodenal microbiome associated with GHBT. Additionally, test if the duodenal microbiome correlates with the fecal microbiome in GHBT positive infants. Plan: We will perform 16S rDNA V4 sequencing on duodenal and fecal samples from Bangladeshi children with and without a positive GHBT. In a subset, we will also perform metagenomic sequencing to investigate how this dysbiosis affects the metabolic function of the enteric microbiome, focusing on hydrogen production and consumption. Mentor/Co-Mentor(s), and Collaborator(s): The primary mentor of this K23, Dr. William Petri, has a 30-year record of NIH Funding and excellent mentorship. My advisory committee and collaborators include experts in microbiome studies, enteric pathogens, malnutrition, environmental enteropathy, and pediatric investigation. Environment and Institutional Commitment to the Candidate: I have access to fantastic resources at VCU, the University of Virginia, and The International Centre for Diarrhoeal Disease Research, Bangladesh. I have a strong commitment from my department and division assuring 75% protected research time and support of my continued mentorship under Dr. Petri at the University of Virginia. Further, the Dean of Research at the VCU School of Medicine sits on my advisory committee demonstrating phenomenal institutional support.