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

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 流行病学研究的证据表明，饮食干预会影响与年龄相关的认知功能。 老年痴呆症（AD）的发病机制本项目旨在测试 对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，以及 认知能力下降，并研究机制和分子层之间的相互关系， 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 肠道微生物组组成。事实上，饮食影响肠道微生物群是公认的 结构和功能，反过来又可以对宿主代谢产生各种各样的生物学效应， 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 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 有前所未有的机会，扩大这项工作，通过检查饮食干预的影响， 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。具体而言，本项目将利用样本 在三个不同的临床试验中收集：MIND，美国POINTER和BEAT-AD。其中两项研究将评估 MIND饮食的影响，这是地中海和DASH（饮食方法停止 高血压）饮食，并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）将测试改良的地中海生酮饮食的效果 （MMKD）。该项目将分析从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。这些研究预计 通过强调以下方面的关键作用，增加我们对AD发病机制和潜在治疗方法的了解： 饮食和微生物群-脑轴，支持我们努力确定潜在的治疗靶点。

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.