The Effects of Diet on the Gut Microbiome and Short Chain Fatty Acids

项目摘要 Noel Theodore Mueller，博士，公共卫生硕士，约翰霍普金斯大学彭博公共卫生学院流行病学助理教授。他寻求获得K01奖，以获得对他从一名擅长在观察性流行病学队列中进行二次数据分析的早期职业科学家过渡到分析和进行旨在干预导致心脏代谢性疾病的微生物群落的试验的独立科学家至关重要的技能、知识和指导研究经验。他过渡到研究独立性的两个基本组成部分是1)临床试验和翻译微生物组实验的进行和设计以及2)高维微生物组数据的分析和解释方面的实践指导培训。拟议的K01职业发展计划将实现这些目标。 与预防心脏代谢性疾病相关的最令人兴奋的研究领域之一与饮食-肠道微生物组关系的病因学作用有关。肠道微生物群作为预防和治疗的靶标的研究对公共卫生来说是一个有趣的领域，因为与人类基因组不同，肠道微生物群是可以修改的。观察研究、小鼠模型和小规模试验表明，饮食因素可能通过改变肠道微生物区系对宿主的健康产生许多影响。然而，需要在人体上进行大规模的严格试验，以确定饮食干预对肠道微生物区系的影响，以及肠道微生物区系的变化是否与治疗相关的心脏代谢健康改善有关。这项应用的总体目标是在随机试验环境中检查饮食干预对不同种族参与者肠道微生物区系及其短链脂肪酸代谢物的影响。第二个目标是探索饮食引起的肠道微生物区系及其代谢物的变化是否与血压的变化有关。 Mueller博士将在约翰霍普金斯大学韦尔奇预防、流行病学和临床研究中心以及JHSPH流行病科丰富的培训环境中开展这项研究，并在JHSPH和JHSPH韦尔奇中心主任、JHSPH医学和流行病学教授劳伦斯·阿佩尔博士(医学硕士)和共同导师辛西娅·西尔斯博士(医学博士)的合作和支持下进行这项研究。在米勒博士的导师、共同导师和顾问的支持下，他能够很好地完成拟议的活动。除了领导这项研究，米勒博士还将参加课程、研讨会、研讨会、科学会议，并与他的导师一起参加每周的学习活动。这种有指导的培训将使米勒博士成长为一名独立的研究人员，在微生物组研究的设计、实施和分析方面拥有专业知识，重点是了解营养和微生物组在心脏代谢疾病中的交叉作用。

PROJECT ABSTRACT Noel Theodore Mueller, PhD, MPH, is an Assistant Professor of Epidemiology at the Johns Hopkins Bloomberg School of Public Health (JHSPH). He seeks a K01 Award to obtain the skill set, knowledge and mentored research experience critical for his transition from an early career scientist adept in conducting secondary data analyses in observational epidemiologic cohorts to an independent scientist who analyzes and conducts trials designed to intervene on microbial communities that contribute to cardiometabolic disease. Two essential components of his transition into research independence are hands-on mentored training in 1) the conduct and design of clinical trials and translational microbiome experiments and 2) the analysis and interpretation of high-dimensional microbiome data. The proposed K01 Career Development plan will accomplish these goals. One of the most exciting areas of investigation related to prevention of cardiometabolic disease pertains to the etiologic role of the diet-gut microbiome relationship. Research on the gut microbiome as a target for prevention and therapy is an intriguing arena for public health because unlike the human genome, the gut microbiome is modifiable. Observational studies, murine models and small trials suggest dietary factors may exert many of their health effects in the host through modification of the gut microbiota. However, large rigorous trials in humans are needed to determine the effect of diet interventions on the gut microbiota, and whether changes to the gut microbiota associate with treatment-related improvements in cardiometabolic health. The overall objective of this application is to examine the effects of dietary interventions on the gut microbiota and their short chain fatty acid metabolites in racially-diverse participants in randomized trial settings. A secondary objective is to explore if diet-induced changes in the gut microbiota and their metabolites are associated with changes in blood pressure. Dr. Mueller will carry out this research in the rich training environment of the Johns Hopkins Welch Center for Prevention, Epidemiology and Clinical Research and the JHSPH Department of Epidemiology, under the collaborative and supportive mentorship of Dr. Lawrence Appel, MD, MPH, Director of the Welch Center and Professor of Medicine and Epidemiology at the JHSOM and JHSPH; and co-mentor Dr. Cynthia Sears, MD, Professor of Medicine in the Division of Infectious Disease and Gastroenterology. With the support of Dr. Mueller’s mentor, co-mentor and advisors, he is well positioned to complete the proposed activities. In addition to leading this research, Dr. Mueller will attend courses, workshops, seminars, scientific meetings, and participate in weekly study activities with his mentors. This mentored training will enable Dr. Mueller to grow into an independent researcher, with expertise in the design, conduct and analysis of microbiome studies, focused on understanding the intersecting role of nutrition and the microbiome in cardiometabolic diseases.