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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.

项目总结