The contribution of antibiotic exposure in the prenatal, peripartum and infancy period to intestinal microbiome perturbations and association with early childhood obesity.

这里提出的研究计划是为了支持医学博士Suchitra Hourigan发展成为 旨在对肠道微生物组的作用进行新颖和变革性研究的独立调查者 儿童早期健康和疾病方面的发展，重点是肥胖。她寻求K23奖项是为了 获得对她的过渡至关重要的技能、知识、正规培训和有指导的研究经验 从早期的内科医生和科学家，在试验设计、招募、 流行病学和微生物组分析交给一位独立科学家，他进行旨在干预的试验 对导致儿童疾病的微生物群落的影响。她过渡到 研究独立性是在1)试验和翻译的进行和设计方面的实践指导培训 微生物组研究和2)纵向微生物组分析与RICH相结合的解释 流行病学数据。拟议的K23职业发展计划将实现这些目标。 肥胖是一种世界性的流行病。在生命的早期阶段，有一个关键的窗口被认为是可以预测的 未来肥胖风险的增加，部分原因是肠道微生物组和代谢编程的建立 发生。流行病学研究表明，早期接触抗生素会增加儿童患病的风险。 肥胖。据推测，早期接触抗生素会导致有害的肠道微生物区系紊乱， 在停用抗生素后仍持续存在的易肥胖代谢表型的宿主； 然而，这在人类身上从未出现过。为了验证这一假设，前瞻性纵向研究 需要进行微生物组分析。该项目的总体目标是确定以下各项的相对贡献 产前、围产期和婴儿期抗生素暴露对肠道微生物群的扰动和 与儿童早期肥胖有关。这将通过利用独一无二的 在Inova建立了纵向队列研究(NIH-NICHD ECHO 4UH3OD023337-03)。 胡里根博士将在英诺瓦转化医学丰富的研究环境中实施这一建议 她在约翰·霍普金斯医学院接受了额外的培训，目前仍是该学院的教员。 在她的主要导师John Niederhuber博士的合作和支持下，医学博士(执行 伊诺瓦卫生系统副总裁兼基因组和生物信息学研究所首席执行官 Inova)，共同导师Cynthia Sears博士，医学博士(传染病和 作为约翰·霍普金斯大学的胃肠病专家)和顾问，她完全有能力完成提议的活动。在……里面 除了领导这项研究，胡里根博士还将参加课程、研讨会、科学会议和 和她的导师一起参加每周的学习活动。这种有指导的培训将使胡里根博士能够成长 成为一名独立的研究人员，在纵向微生物组的设计、实施和分析方面具有专业知识 研究的重点是了解发育中的肠道微生物群在儿童健康结果中的作用。

The research program proposed herein is to support the development of Suchitra Hourigan, MD, into an independent investigator aiming to conduct novel and transformative research into the role of gut microbiome development in early childhood health and disease, with a focus on obesity. She seeks a K23 award in order to obtain the skill set, knowledge, formalized training and mentored research experience critical for her transition from an early career physician-scientist with a solid foundation in the basics of trial design, recruitment, epidemiology and microbiome analysis to an independent scientist who conducts trials designed to intervene on microbial communities that contribute to childhood disease. Two essential components of her transition into research independence are hands-on mentored training in 1) the conduct and design of trials and translational microbiome studies and 2) the interpretation of longitudinal microbiome analysis combined with rich epidemiological data. The proposed K23 Career Development plan will accomplish these goals. Obesity is a worldwide epidemic. There is a critical window in very early life that is conjectured to be predictive of later obesity risk, in part due to the establishment of the gut microbiome and metabolic programming that occur. Epidemiological studies have indicated that early exposure to antibiotics increases the risk of childhood obesity. It is hypothesized that early antibiotic exposure causes detrimental gut microbiota perturbations that ‘program’ the host to an obesity-prone metabolic phenotype which persists after discontinuation of antibiotics; however this has never been shown in humans. To test this hypothesis, prospective longitudinal studies with microbiome analysis are needed. The overall goal of this project is to determine the relative contributions of antibiotic exposure in the prenatal, peripartum and infancy period to intestinal microbiome perturbations and association with early childhood obesity. This will be achieved by leveraging the infrastructure of the unique established longitudinal cohort study at Inova (NIH-NICHD ECHO 4UH3OD023337-03). Dr. Hourigan will carry out this proposal in the rich research environment of the Inova Translational Medicine Institute with additional training at the Johns Hopkins School of Medicine where she remains a faculty member. Under the collaborative and supportive mentorship of her primary mentor Dr. John Niederhuber, MD (Executive Vice President of the Inova Health System and CEO of the Genomics and Bioinformatics Research Institute at Inova), co-mentor Dr. Cynthia Sears, MD (Professor of Medicine in the Division of Infectious Disease and Gastroenterology, Johns Hopkins) and advisors, she is well positioned to complete the proposed activities. In addition to leading this research, Dr. Hourigan will attend courses, workshops, scientific meetings and participate in weekly study activities with her mentors. This mentored training will enable Dr. Hourigan to grow into an independent researcher, with expertise in the design, conduct and analysis of longitudinal microbiome studies, focused on understanding role of the developing gut microbiome in childhood health outcomes.