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.

项目总结 作为疾病预防和治疗靶点的肠道微生物群研究是一个耐人寻味的领域 健康，因为微生物及其代谢物是可以改变的。观察性研究、小鼠模型和 很少有人体试验表明，饮食因素通过修饰在宿主体内发挥了许多健康作用。 肠道微生物组及其相关的代谢物。此外，早期证据表明，微生物群和 代谢组改变饮食干预对健康结果的影响，表明微生物组和 代谢组在精确营养中起作用。然而，在人类身上进行严格控制的喂养试验仍然是 需要确定全日粮转换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饰或调节饮食对心血管危险因素的影响，包括 血压。特别令人感兴趣的是饮食模式和钠(Na+)摄入量的影响。 这项研究的主要目的是检查美国心脏协会推荐的 停止高血压(DASH)饮食的饮食方法(与典型的美国饮食相比)和降低饮食中的Na+ 肠道微生物组和非靶向和靶向代谢组的摄入量与较高的膳食Na+摄入量- 包括短链脂肪酸--在登记了DASH4D的成年2型糖尿病患者的多种族队列中 试验-最近资助的一项随机、交叉、受控喂养试验。次要目标是探索是否 肠道微生物区系及其代谢物改变和/或调节饮食模式和钠对血液的影响 压力，从而告知精确的营养。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式元基因组学、高通量代谢组学分析，以及 短链脂肪酸代谢物的靶向定量。我们将联合调查微生物组和 在喂养试验的每个饮食时期之前和之后采集的粪便和血液中的代谢物测量。 Mueller博士(PI)将与一组杰出的跨学科合作研究人员一起进行这项研究 约翰霍普金斯大学韦尔奇预防、流行病学和医疗中心的协作和卓越环境 临床研究和彭博公共卫生学院。米勒博士的合作调查员已经 在喂养试验(APEPL)、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)。在米勒博士研究的支持下 作为团队的一员，他能够很好地完成提议的活动。这些发现有很大的潜力：(A)确定 坚持DASH饮食和降低膳食Na+摄入量的客观措施；(B)揭示新的机制 饮食模式和钠离子摄入量对血压的影响；(C)提供新的疾病预防策略和 治疗的可能性和；(D)告知利用微生物组-代谢组关系进行精确营养。