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 - 受控饮食对肠道微生物组，代谢组和认知的影响 功能 流行病学研究的证据表明，饮食干预会影响与年龄相关的认知 下降以及阿尔茨海默氏病（AD）的发展。该项目旨在测试 关于肠道微生物组组成和功能，血液和粪便代谢组的不同饮食干预措施，以及 认知下降和研究与 这些影响。介导饮食对脑部健康有益影响的一种可能的机制可能是通过变化 肠道微生物组组成。确实，饮食会影响肠道微生物群社区的良好成就 结构和功能反过来可能对宿主代谢有多种生物学作用 免疫系统。最近的研究表明，肠道菌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）和阿尔茨海默氏病加速医学伙伴关系 （AMP-AD）已经确定了与AD和AD进展标记相关的代谢特征。我们现在 通过研究饮食干预措施对 微生物组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与广告相关的结果有关。具体来说，该项目将使用样本 在三个不同的临床试验中收集：Mind，美国指针和Beat-AD。两项研究将评估。 思维饮食的影响，这是地中海和破折号的杂种（饮食方法停止的方法 高血压）基于对大脑健康影响的科学证据进行修改的饮食（Mind，美国） 指针）。第三次试验（BEAT-AD）将测试改良的地中海酮饮食的影响 （MMKD）。该项目将介绍从1,700多名参与者中收集的血液和粪便样本 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 预先定义的AD代谢特征，大脑结构和功能以及行为。这些研究是预期的 通过强调关键作用 饮食和微生物脑轴轴，支持我们努力确定潜在的治疗靶标。