Effects of Dietary Patterns and Sodium Intake on the Gut Microbiome and Metabolome

饮食模式和钠摄入量对肠道微生物组和代谢组的影响

基本信息

批准号：
10888821
负责人：
NOEL T MUELLER
金额：
$ 73.12万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-06-01 至 2028-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10888821
关键词：
Acetates Address Adherence Adopted Adult American Heart Association Ancillary Study Animal Model Animals Bacteria Bioinformatics Biological Factors Black race Blood Blood Pressure Butyrates Cardiovascular Diseases Cause of Death Clinical Research Control Groups Crossover Design DASH diet Data Development Diet Dietary Factors Dietary Intervention Dietary Practices Dietary Sodium Disease Enrollment Environment Etiology Eubacterium Feces Fiber Funding Goals Health Health Promotion Heterogeneity Human Hypertension Individual Intake Intestines Knowledge Measures Mediating Metagenomics Microbe Modification National Heart, Lung, and Blood Institute Non-Insulin-Dependent Diabetes Mellitus Observational Study Outcome Outcome Measure Participant Pathogenicity Pathway interactions Pattern Population Heterogeneity Positioning Attribute Prevention Research Prevention strategy Probiotics Propionates Proteobacteria Public Health Public Health Schools Race Randomized Recommendation Research Research Design Research Personnel Research Project Summaries Role Serum Shotguns Sodium Sum Testing Therapeutic Volatile Fatty Acids blood pressure elevation blood pressure reduction cardiovascular disorder prevention cardiovascular risk factor cohort dietary dietary control dietary guidelines disorder prevention dysbiosis epidemiology study fecal microbiota feeding genome sequencing gut microbes gut microbiome gut microbiota host microbiome improved interest metabolome metabolomics microbial microbiome microbiota microorganism mouse model multi-racial novel prebiotics precision nutrition prevent racial diversity randomized trial recruit secondary analysis sex statistics treatment response whole genome

项目摘要

PROJECT SUMMARY Research on the gut microbiome as a target for disease prevention and therapy is an intriguing arena for public health because microbes and their metabolites are modifiable. Observational studies, murine models and a few trials in humans suggest dietary factors exert many of their health effects in the host through modification of the gut microbiome and its associated metabolome. Moreover, early evidence indicates the microbiome and metabolome modify the effects of diet interventions on health outcomes, suggesting the microbiome and metabolome have a role in precision nutrition. However, rigorously controlled feeding trials in humans are still needed to determine the effects of whole diet inverventions on the microbiome and metabolome, and to test if the microbiome and metabolome modify or mediate the effects of diet on cardiovascular risk factors, including blood pressure. Of particular interest are the effects of dietary patterns and level of sodium (Na+) intake. The primary objective of this study is to examine the effects of the American Heart Association recommended Dietary Approaches to Stop Hypertension (DASH) diet (compared to a typical US diet) and lower dietary Na+ intake vs. higher dietary Na+ intake on the gut microbiome and the untargeted and targeted metabolome— including short chain fatty acids—in a multi-racial cohort of adults with type 2 diabetes enrolled in the DASH4D trial – a recently funded randomized, cross-over, controlled feeding trial. A secondary objective is to explore if the gut microbiota and their metabolites modify and/or mediate the effects of diet patterns and sodium on blood pressure, thusly informing precision nutrition. We will also examine if effects vary by sex and race. In particular, we propose to perform whole genome shotgun metagenomics, high-throughput metabolomics profiling, and targeted quantification of short chain fatty acid metabolites. We will jointly investigate the microbiome and metabolome measured in stool and blood collected before and after each of the diet periods in the feeding trial. Dr. Mueller (PI) will carry out this research with an outstanding group of interdisciplinary co-investigators in the collaborative and eminent environments of the Johns Hopkins Welch Center for Prevention, Epidemiology and Clinical Research and the Bloomberg School of Public Health. Dr. Mueller’s co-investigators have complementary expertise in feeding trials (Appel), microbiome statistics (Zhao), metabolomics (Rebholz), bioinformatics (Bittinger), and short chain fatty acids (Pluznick). With the support of Dr. Mueller’s research team, he is well positioned to complete the proposed activities. The findings have great potential to: (a) identify objective measures of adherence to the DASH diet and lower dietary Na+ intake; (b) reveal novel mechanisms underlying the BP effects of dietary patterns and Na+ intake; (c) offer new disease prevention strategies and therapeutic possibilities and; (d) inform use of the microbiome-metabolome nexus for precision nutrition.

项目摘要肠道微生物组作为疾病预防和治疗的靶标的研究是一个有趣的公众领域健康，因为微生物及其代谢物是可修改的。观察性研究，鼠模型和人类中很少有试验表明饮食因素通过修改在宿主中发挥许多健康影响肠道微生物组及其相关的代谢组。此外，早期证据表明微生物组和代谢组改变了饮食干预对健康结果的影响，暗示了微生物组和代谢组在精确营养中起作用。但是，在人类中进行严格控制的喂养试验仍在需要确定整个饮食不可侵化对微生物组和代谢组的影响，并测试是否微生物组和代谢组修改或介导饮食对心血管危险因素的影响，包括血压。特别有趣的是饮食模式和钠（NA+）摄入水平的影响。这项研究的主要目的是检查美国心脏协会的影响饮食方法停止高血压（与典型的美国饮食相比）和降低饮食NA+ 在肠道微生物组和未靶向和靶向代谢组的摄入量与较高的饮食NA+摄入量 - 包括短链脂肪酸 - 在Dash4d中注册的2型糖尿病的成年人组中试验 - 最近资助的随机，交叉，受控的喂养试验。次要目标是探索是否肠道菌群及其代谢物修饰和/或介导饮食模式和钠对血液的影响压力，从而告知精度营养。我们还将检查影响与种族的影响是否有所不同。尤其，我们建议执行整个基因组shot弹枪宏基因组学，高通量代谢组学分析和靶向短链脂肪酸代谢产物的靶向量。我们将共同研究微生物组和在喂养试验中，在每个饮食期之前和之后收集的凳子和血液中测量的代谢组。 Mueller博士（PI）将与一组出色的跨学科共同研究员进行这项研究约翰·霍普金斯·韦尔奇（John Hopkins Welch）预防，流行病学和临床研究和彭博公共卫生学院。穆勒博士的共同研究者有完全专业的进食试验（Appel），微生物组统计（ZHAO），代谢组学（Rebholz），生物信息学（Bittinger）和短链脂肪酸（Pluznick）。在穆勒博士的研究的支持下团队，他在完成拟议的活动方面处于良好状态。这些发现具有很大的潜力：（a）确定遵守破折号饮食和降低饮食NA+摄入量的客观度量；（b）揭示新的机制饮食模式和NA+摄入量的BP效应的基础；（c）提供新的疾病预防策略和治疗可能性和；（d）告知使用微生物组 - 代谢组Nexus进行精确营养。