Towards Precision Nutrition for Alzheimer's Dementia Prevention: A Prospective Study of Dietary Patterns, the Gut Microbiome and Cognitive Function
预防阿尔茨海默病的精准营养:饮食模式、肠道微生物组和认知功能的前瞻性研究
基本信息
- 批准号:10447872
- 负责人:
- 金额:$ 91.75万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-06-01 至 2027-03-31
- 项目状态:未结题
- 来源:
- 关键词:AcidsAddressAdherenceAdultAlzheimer disease preventionAlzheimer&aposs DiseaseAlzheimer&aposs disease related dementiaAlzheimer&aposs disease riskAmyloidAmyloid beta-42Amyloid beta-ProteinAnimal ModelBifidobacteriumBile AcidsBioinformaticsBiological MarkersBiometryBrain-Derived Neurotrophic FactorBranched-Chain Amino AcidsButyratesCognitionCognitiveCohort StudiesDataDementiaDeoxycholic AcidDietDietary AssessmentDietary InterventionDietary PracticesEnzymesEpidemiologyFlavonoidsFoundationsGlial Fibrillary Acidic ProteinHealthHumanHuman MicrobiomeImpaired cognitionIndividualIndividual DifferencesInterventionKnowledgeKynurenineLactobacillusLightLinkMagnetic Resonance ImagingMeasuresMediatingMediterranean DietMetabolicMetabolismMetagenomicsMicrobial TaxonomyMolecularNerve DegenerationNeurologyNurses&apos Health StudyOutcome AssessmentParticipantPeptidesPlasmaPopulationPositioning AttributePreventionProductionProspective StudiesRandomizedReportingReproducibilityResearchResearch DesignResearch PriorityResolutionResourcesRiskRoleSamplingShotgunsTaxonomyTechnologyTimeVolatile Fatty Acidsadjudicateagedbaseblood-brain barrier permeabilizationbrain magnetic resonance imagingcognitive functioncohortcost efficientdesigndietarydietary approachfollow-upgamma-Aminobutyric Acidgut microbiomegut microbiotaimprovedindexingindividual variationindividualized preventioninsightmetabolomicsmetatranscriptomicsmicrobialmicrobial compositionmicrobiomemild cognitive impairmentmolecular phenotypeneurofilamentnovelnovel markernutritionpersonalized approachprecision medicineprecision nutritionpredictive markerrandomized trialresponsesystemic inflammatory responsetrimethyloxamine
项目摘要
PROJECT SUMMARY
This proposal directly addresses a high-priority research topic, “Enabling precision medicine for
Alzheimer’s disease and related dementias through deep molecular phenotyping”, for PAR-19-070, Research
on Current Topics in Alzheimer's Disease and Its Related Dementias, by beginning to develop precision dietary
approaches for AD prevention through integrating multiple molecular data types. The potential for healthy
dietary patterns to maintain cognitive health is supported by cohort studies and a randomized trial. However,
these healthy dietary patterns were developed based on population averages and may not be best suited for a
given individual. Preliminary data from our group and others support the rationale to study personalized
approaches tailored to individual gut microbiomes to improve dietary prevention of Alzheimer’s dementia (AD).
However, no study has examined modifying and mediating roles of the gut microbiome in the diet-cognition
association. The few human studies of the gut microbiome in AD were limited by small size, cross-sectional
design, and lack of high-resolution microbial functional profiling. This background supports our central
hypotheses that 1) healthy dietary patterns contribute to cognitive health partly through modulating the gut
microbiome; and 2) associations of the dietary patterns with cognitive function vary by individuals’ gut microbial
profiles. This proposal represents a highly cost-efficient, prospective study leveraging existing fecal
samples/microbiome data and cognitive function assessments in three studies with complementary strengths
in study design, and diet and outcome assessments: the Nurses’ Health Study II (NHSII, n =1,500) with
decades-long repeated dietary assessments and extended follow-up, the Mediterranean-DASH Intervention for
Neurodegenerative Delay (MIND) Trial with randomized dietary interventions (n =604), and the ASPREE-XT
Study (n =13,000) with adjudicated incident AD endpoints. To gain more advanced mechanistic insights, we
will take a multi’omic approach to combine shotgun metagenomics and metatranscriptomics to profile the
microbial composition and enzymatic function, and fecal metabolomics to measure the microbiome metabolic
activity. We will investigate roles of gut microbial composition and enzymatic function in the associations of the
Mediterranean diet (MedDiet) and the MIND Diet with cognitive function (Aim 1) and examine the
interrelationships among the two healthy dietary patterns, the metabolic activity of the gut microbiome and
cognitive function (Aim 2) in the NHSII. We will replicate findings from Aims 1 and 2 in ASPREE-XT and the
MIND Trial (Aim 3). This project will generate reproducible, translational evidence on gut microbial and fecal
metabolomic features that explain inter-individual heterogeneity in response to healthy dietary patterns and
provide foundational knowledge for maximizing the benefits of dietary approaches, discovering novel predictive
biomarkers, and ultimately contributing to precision prevention of AD.
项目摘要
该提案直接解决了一个高优先级的研究课题,即“使精准医疗能够
通过深层分子表型分析阿尔茨海默病和相关痴呆”,PAR-19-070,研究
关于阿尔茨海默病及其相关痴呆症的当前主题,开始开发精确的饮食,
通过整合多种分子数据类型来预防AD。健康的潜力
维持认知健康的饮食模式得到了队列研究和随机试验的支持。然而,在这方面,
这些健康的饮食模式是根据人口平均水平制定的,
给予个人。来自我们小组和其他人的初步数据支持研究个性化的基本原理。
针对个体肠道微生物组的方法,以改善阿尔茨海默氏痴呆症(AD)的饮食预防。
然而,没有研究检查肠道微生物组在饮食认知中的调节和介导作用
协会对AD患者肠道微生物组的少数人体研究受到小规模、横断面研究的限制。
设计,以及缺乏高分辨率的微生物功能分析。这一背景支持我们的中央
假设1)健康的饮食模式有助于认知健康,部分通过调节肠道
2)饮食模式与认知功能的关联因个人的肠道微生物而异。
数据区.该提案代表了一项利用现有粪便的高成本效益的前瞻性研究。
三项优势互补的研究中的样本/微生物组数据和认知功能评估
研究设计、饮食和结果评估:护士健康研究II(NHSII,n = 1,500),
长达数十年的重复饮食评估和延长随访,Mediterranean DASH干预,
采用随机饮食干预的神经退行性延迟(MIND)试验(n =604)和ASPREE-XT
研究(n = 13,000)具有裁定的AD事件终点。为了获得更先进的机械见解,我们
将采用多组学方法,将联合收割机鸟枪宏基因组学和元转录组学结合起来,
微生物组成和酶功能,以及粪便代谢组学,以测量微生物组代谢
活动我们将研究肠道微生物组成和酶的功能在这些疾病之间的关系中的作用。
地中海饮食(MedDiet)和MIND饮食与认知功能(Aim 1),并检查
两种健康饮食模式之间的相互关系,肠道微生物组的代谢活动,
NHSII中的认知功能(目标2)。我们将在ASPREE-XT中复制目标1和2的结果,
MIND试验(目标3)。该项目将产生有关肠道微生物和粪便的可重复的、转化的证据
代谢组学特征,解释了健康饮食模式的个体间异质性,
为最大限度地发挥饮食方法的益处提供基础知识,发现新的预测方法,
生物标志物,并最终有助于精确预防AD。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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{{ truncateString('Dong Wang', 18)}}的其他基金
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10493258 - 财政年份:2021
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10178327 - 财政年份:2020
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