Project 2 - Influence of controlled diets on gut microbiome, metabolome and cognitive function

项目 2 - 控制饮食对肠道微生物组、代谢组和认知功能的影响

• 批准号: 10693930
• 负责人: Rima F Kaddurah-Daouk
• 金额: $ 90.18万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-15 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10693930
• 关键词: Acceleration; Aerobic Exercise; Affect; Age; Age-associated memory impairment; Alzheimer' s Disease; Alzheimer’s disease biomarker; Amino Acids; Amyloid beta-Protein; Behavior; Bile Acids; Biological; Blood; Brain; Carbohydrates; Cardiovascular system; Chronic; Clinical Trials; Cognition; Cognitive; Communities; DASH diet; Data; Development; Diabetes Mellitus; Diet; Dietary Intervention; Disease; Disease Marker; Disease Progression; Education; Endocrine system; Energy-Generating Resources; Ethnic Origin; Fat-Restricted Diet; Genotype; Goals; Heterogeneity; Hormonal; Hybrids; Hypertension; Immune; Immune system; Impaired cognition; Impairment; Intervention; Intervention Trial; Intractable Epilepsy; Ketones; Late Onset Alzheimer Disease; Life Style; Mediating; Medicine; Memory; Metabolic; Metabolic Diseases; Metabolism; Metagenomics; Mind; Modification; Molecular; Molecular Profiling; Nerve Degeneration; Neurons; Obesity; Outcome; Participant; Pathogenesis; Patients; Pilot Projects; Plants; Prevention; Preventive; Race; Randomized, Controlled Trials; Research; Risk; Role; Sample Size; Sampling; Signal Transduction; Sphingolipids; Structure; Systems Analysis; Systems Biology; Techniques; Technology; Testing; Therapeutic; Variant; Work; acylcarnitine; base; brain health; cardiovascular risk factor; cognitive function; cognitive training; cohort; design; dietary; epidemiology study; fecal metabolome; glucose uptake; gut microbiome; gut microbiota; gut-brain axis; hypercholesterolemia; improved; intestinal barrier; ketogenic diet; lifestyle intervention; metabolome; metabolomics; microbiome composition; microbiota; microbiota metabolites; middle age; mild cognitive impairment; neural; neuropsychiatric symptom; nutrition; participant enrollment; post intervention; precision medicine; prevent; programs; response; sex; social; tau Proteins; therapeutic target; volunteer

ABSTRACT – Project 2 – Influence of controlled diets on gut microbiome, metabolome and cognitive function There is evidence from epidemiological studies that dietary interventions influence age-associated cognitive decline as well as the development of Alzheimer’s disease (AD). This Project is designed to test the effects of different dietary interventions on gut microbiome composition and function, blood and fecal metabolomes, and cognitive decline and investigate the mechanism(s) and interrelations between molecular layers that relate to these effects. One possible mechanism mediating beneficial effects of diet on brain health may be via changes to gut microbiome composition. Indeed, it is well-established that diet impacts the gut microbiota community structure and function which in turn can have a wide variety of biological effects on host metabolism and the immune system. Recent studies suggest that gut microbiota may also affect brain function. The Alzheimer’s Disease Metabolomics Consortium (ADMC) and the Accelerated Medicine Partnership for Alzheimer’s disease (AMP-AD) have identified metabolic signatures that correlate with markers of AD and AD progression. We now have the unprecedented opportunity to expand on this work by examining the effect of dietary interventions on microbiome composition and function, as well as metabolic signatures in order to understand how these effects relate to cognitive decline and other AD-relevant outcomes. Specifically, this Project will utilize samples collected in three different clinical trials: MIND, U.S. POINTER, and BEAT-AD. Two of the studies will evaluate effects of the MIND diet, which is a hybrid of the Mediterranean and DASH (dietary approaches to stop hypertension) diets with modifications based on scientific evidence of effects on brain health (MIND, U.S. POINTER). The third trial (BEAT-AD) will test the effects of the Modified Mediterranean-Ketogenic Diet (MMKD). This Project will profile blood and fecal samples collected from more than 1,700 participants enrolled in the three different clinical trials using state-of-the art metagenomics and metabolomics technologies to define the effects of each dietary intervention on gut microbiome, metabolome and relate these outcomes to pre-defined AD metabolic signatures, brain structure and function, and behavior. These studies are expected to increase our understanding of AD pathogenesis and potential treatments, by highlighting the crucial role of diet and the microbiota-brain axis, supporting our endeavors to identify potential therapeutic targets.

摘要 – 项目 2 – 控制饮食对肠道微生物组、代谢组和认知的影响 功能 流行病学研究证据表明，饮食干预会影响与年龄相关的认知能力 下降以及阿尔茨海默病（AD）的发展。该项目旨在测试以下效果 对肠道微生物组成和功能、血液和粪便代谢组的不同饮食干预，以及 认知能力下降并研究与相关的分子层之间的机制和相互关系 这些影响。调节饮食对大脑健康有益影响的一种可能机制可能是通过改变 肠道微生物组的组成。事实上，饮食影响肠道微生物群落已是公认的事实 结构和功能反过来又可以对宿主代谢和 免疫系统。最近的研究表明肠道微生物群也可能影响大脑功能。阿尔茨海默氏症 疾病代谢组学联盟 (ADMC) 和阿尔茨海默病加速医学合作伙伴关系 (AMP-AD) 已经确定了与 AD 和 AD 进展标志物相关的代谢特征。我们现在 通过检查饮食干预对健康的影响，我们有前所未有的机会来扩展这项工作。 微生物组的组成和功能，以及代谢特征，以了解这些影响如何 与认知能力下降和其他 AD 相关结果有关。具体来说，该项目将利用样本 在三个不同的临床试验中收集：MIND、U.S. POINTER 和 BEAT-AD。其中两项研究将评估 MIND 饮食法的效果，该饮食法是地中海饮食法和 DASH 饮食法（旨在阻止 高血压）饮食根据对大脑健康影响的科学证据进行修改（MIND，美国） 指针）。第三项试验（BEAT-AD）将测试改良地中海生酮饮食的效果 （MMKD）。该项目将对从超过 1,700 名参与者收集的血液和粪便样本进行分析 在三个不同的临床试验中，使用最先进的宏基因组学和代谢组学技术 定义每种饮食干预对肠道微生物组、代谢组的影响，并将这些结果与 预定义的 AD 代谢特征、大脑结构和功能以及行为。这些研究预计 通过强调 AD 发病机制和潜在治疗方法的关键作用 饮食和微生物群-大脑轴，支持我们努力确定潜在的治疗靶点。