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

• 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
• 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

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 研究肠道微生物组作为疾病预防和治疗的目标是公众感兴趣的竞技场 因为微生物及其代谢物是可以改变的。观察性研究、鼠模型和 在人类身上进行的一些试验表明，饮食因素通过改变对宿主的健康产生许多影响。 肠道微生物组及其相关代谢物组。此外，早期的证据表明， 代谢组改变饮食干预对健康结果的影响，这表明微生物组和 代谢组在精确营养中发挥作用。然而，严格控制的人类喂养试验仍然存在。 需要确定整个饮食转化对微生物组和代谢组的影响，并测试 微生物组和代谢组改变或介导饮食对心血管风险因素的影响，包括 血压.特别令人感兴趣的是饮食模式和钠（Na+）摄入水平的影响。 本研究的主要目的是检查美国心脏协会推荐的 阻止高血压的饮食方法（DASH）饮食（与典型的美国饮食相比）和较低的饮食钠+ 摄入量与较高的饮食Na+摄入量对肠道微生物组以及非靶向和靶向代谢组的影响- 包括短链脂肪酸-在DASH 4D中登记的多种族2型糖尿病成人队列中 试验-最近资助的随机，交叉，控制喂养试验。第二个目标是探索 肠道微生物群及其代谢物改变和/或介导饮食模式和钠对血液的影响 压力，从而通知精确营养。我们还将研究影响是否因性别和种族而异。特别是， 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， 短链脂肪酸代谢物的靶向定量。我们将共同研究微生物组， 在喂养试验中的每个饮食期之前和之后收集的粪便和血液中测量的代谢组。 博士Mueller（PI）将与一组杰出的跨学科合作研究者一起开展这项研究， 约翰霍普金斯韦尔奇预防、流行病学和 临床研究和彭博公共卫生学院。穆勒博士的合作研究者 喂养试验（阿佩尔）、微生物组统计（赵）、代谢组学（Rebholz）、 生物信息学（Bittinger）和短链脂肪酸（Pluznick）。在穆勒博士研究的支持下 在团队中，他完全有能力完成拟议的活动。研究结果有很大的潜力：（a）查明 坚持DASH饮食和较低饮食Na+摄入量的客观测量;（B）揭示了新的机制 饮食模式和Na+摄入对BP影响的基础;（c）提供新的疾病预防策略， 治疗的可能性;（d）为精确营养提供微生物组-代谢组关系的使用提供信息。