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.

项目概要将肠道微生物组作为疾病预防和治疗目标的研究对公众来说是一个有趣的领域健康，因为微生物及其代谢物是可改变的。很少有人体试验表明饮食因素通过改变对宿主产生许多健康影响此外，早期证据表明微生物组和其相关的代谢组。代谢组改变饮食干预对健康结果的影响，表明微生物组和代谢组在精准营养中发挥着重要作用，然而，严格控制的人类喂养试验仍在进行中。需要确定整体饮食发明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改变或调节饮食对心血管危险因素的影响，包括特别令人感兴趣的是饮食模式和钠 (Na+) 摄入量的影响。本研究的主要目的是检查美国心脏协会推荐的效果控制高血压的饮食方法 (DASH) 饮食（与典型的美国饮食相比）和较低的膳食 Na+ 摄入量与较高膳食 Na+ 摄入量对肠道微生物组以及非目标和目标代谢组的影响 - 包括短链脂肪酸——在参加 DASH4D 的多种族 2 型糖尿病成人队列中试验——最近资助的一项随机、交叉、对照喂养试验的第二个目标是探讨是否。肠道微生物群及其代谢物改变和/或调节饮食模式和钠对血液的影响我们还将研究压力是否因性别和种族而异。我们建议进行全基因组鸟枪宏基因组学、高通量代谢组学分析，以及我们将共同研究微生物组和短链脂肪酸代谢物的靶向定量。在喂养试验中每个饮食周期之前和之后收集的粪便和血液中测量代谢组。 Mueller 博士（PI）将与一组杰出的跨学科联合研究人员一起开展这项研究约翰·霍普金斯·韦尔奇预防、流行病学和预防中心的协作和卓越环境临床研究和彭博公共卫生学院的穆勒博士的共同研究人员。喂养试验 (Appel)、微生物组统计 (Zhao)、代谢组学 (Rebholz) 方面的互补专业知识，在 Mueller 博士研究的支持下，生物信息学 (Bittinger) 和短链脂肪酸 (Pluznick)。团队中，他完全有能力完成拟议的活动。研究结果具有巨大的潜力：(a) 确定坚持 DASH 饮食和降低膳食 Na+ 摄入量的客观措施 (b) 揭示了新机制；饮食模式和 Na+ 摄入量对血压的影响；(c) 提供新的疾病预防策略和治疗可能性；(d) 告知利用微生物组-代谢组关系进行精准营养。