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

项目摘要 候选人：我是弗吉尼亚联邦大学儿科传染病的助理教授 (VCU)该校拥有一所研究密集型医学院。我在我的导师Dr. 威廉·佩特里4年，有10个出版物，4作为第一作者。我在过去的三年里， 美国热带医学和卫生学会的会议，并从 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：我的目标是成为一名独立资助的 临床研究人员，具有设计和进行试验的专业知识，以了解和减轻 传染病对低收入环境中儿童健康的影响。为此，我将采取几个 临床研究设计与实施课程。我有一个顾问委员会， 与我有着相似兴趣的研究人员在指导年轻科学家方面有着良好的记录。 研究计划：本K23奖项中提出的工作将利用两项现有的队列研究进行 目前由我的导师佩特里博士和我们在孟加拉国的合作者进行。 具体目标1：测试婴儿期GHBT阳性是否预示未来发育迟缓， 孟加拉国儿童的神经发育缺陷。计划：使用正在进行的出生队列，我将测量 GHBT在出生后头两年的四个时间点以及与人体测量结果相关性的试验 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，在GHBT阳性患者中，检测十二指肠微生物组是否与粪便微生物组相关 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16 S rDNA V4测序 有和没有阳性GHBT的孩子。在一个子集中，我们还将进行宏基因组测序， 研究这种生态失调如何影响肠道微生物组的代谢功能，重点是氢 生产和消费。 导师/共同导师和合作者：本K23的主要导师William Petri博士拥有30年的 NIH基金和优秀导师的记录。我的咨询委员会和合作者包括以下方面的专家： 微生物组研究、肠道病原体、营养不良、环境性肠病和儿科调查。 环境和机构对候选人的承诺：我有机会在VCU， 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%的研究时间得到保护，我的 继续在弗吉尼亚大学接受佩特里博士的指导。此外，VCU的研究主任 医学院是我的顾问委员会成员，表现出非凡的机构支持。

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.