The Roles of the Microbiome and Metabolome in Vascular Aging

微生物组和代谢组在血管衰老中的作用

• 批准号: 9018224
• 负责人: Tanika Nicole Kelly
• 金额: $ 16.02万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9018224
• 关键词: Adult; Affect; Age; Aging; Aging-Related Process; Atherosclerosis; Bioinformatics; Biological; Blood Pressure; Blood Vessels; Cardiac; Cardiovascular system; Childhood; Chronic; Clinical; Communities; Cross-Sectional Studies; Data; Development; Diet; Disease; Early identification; Elderly; Fasting; Funding; Health; Heart; Human; Individual; Link; Longevity; Longitudinal Studies; Mass Fragmentography; Measures; Metabolic Marker; Methodology; Methods; Morbidity - disease rate; Participant; Pathway interactions; Phenotype; Plasma; Population; Prevention therapy; Process; Public Health; Public Health Practice; Quality of life; Research; Resources; Ribosomal RNA; Risk Factors; Role; Sampling; Structure; System; Taxon; Techniques; Technology; Testing; Time; United States National Institutes of Health; Vascular Diseases; Work; age related; aged; arterial stiffness; base; cardiovascular disorder prevention; cognitive function; cost effective; follow-up; gut microbiome; gut microbiota; healthy aging; high risk; human study; improved; innovation; insight; intimal medial thickening; metabolome; metabolomics; microbial; microbial community; microbiome; microbiota; mortality; next generation; novel; prevent; probiotic supplementation; public health relevance; sample collection; tool

 DESCRIPTION (provided by applicant): The overall objective of the proposed study is to examine the intersecting roles of the microbiome and metabolome in vascular aging among 300 participants of the Bogalusa Heart Study (BHS). The BHS is an NIH-funded longitudinal study of vascular health across the lifespan. The current follow-up includes 1,257 participants who are undergoing careful assessment of vascular aging parameters, including non- invasive measures of arterial stiffness, subclinical atherosclerosis, central aortic blood pressure, and cardiac structure and function. Taking advantage of these data, we will randomly select 300 participants for microbiome sequencing and metabolome quantification. This sampling strategy will allow us to efficiently and powerfully examine the influence of microbiota and metabolites on multiple parameters of vascular aging, including associations which have not been explored previously. We will use next generation technology to conduct 16S rRNA sequencing of gut microbial communities from fecal samples of BHS participants. Bioinformatics tools will be utilized to transform the large amount of generated raw data to an end-product with information on the relative abundance of identified taxa, as well as composite metrics of microbiota alpha and beta diversity. Individual and overall compositional metrics will be tested for association with vascula aging parameters in multivariable analyses. Through the implementation of state-of-the-art sequencing methods and sophisticated analytic techniques, our research will be among the first to directly explore the relation of microbiota with vascular aging. Untargeted metabolomic profiling will then be conducted using innovative methodology that combines LC-MS and GC-MS technologies. An automated pipeline will be used to process raw metabolomics data into an operational matrix of relative metabolite concentrations. Advanced multivariable methods will be used to test associations of individual metabolites and overall metabolomic profile with vascular aging. Since we will use previously collected plasma samples and phenotype data, the proposed analysis is extremely cost-effective. To better understand the biological pathways linking microbiome to phenotype, we will test whether microbiota influence individual metabolites and metabolomic profiles. This analysis will be among the first to comprehensively explore the relation of gut microbiota to the human plasma metabolite repertoire, contributing critical information on the biological pathways influencing cardiovascular In addition to providing important mechanistic insights into the biological pathways underlying CVD development, the proposed research may aid in the early identification of individuals at high risk for CVD based on their microbiota and metabolomic profiles. Based on this work, tailored strategies may be developed to alter specific vascular aging related microbiota and metabolites, with the potential to promote healthy aging and longevity through the reduction of CVD morbidity and mortality. disease (CVD) progression.

 描述（由适用提供）：拟议的研究的总体目的是检查Bogalusa心脏研究（BHS）300名参与者中微生物组和代谢组在血管老化中的相交作用。 BHS是NIH资助的整个生命周期血管健康的纵向研究。当前的随访包括1,257名参与者，他们正在仔细评估血管衰老参数，包括动脉僵硬，亚临床动脉粥样硬化，中央主动脉血压以及心脏结构和功能的非侵入性测量。利用这些数据，我们将随机选择300名参与者进行微生物组测序和代谢组定量。这种抽样策略将使我们能够有效，有力地检查微生物群和代谢产物对血管衰老多个参数的影响，包括以前尚未探讨的关联。我们将使用下一代技术从BHS参与者的粪便样本中对肠道微生物群落进行16S rRNA测序。生物信息学工具将用于将大量生成的原始数据转换为最终产品，并提供有关已识别分类单元的相对丰度以及Microbiota alpha和Beta多样性的复合指标的信息。在多变量分析中，将测试个体和整体复合指标与Vascula老化参数的关联。通过实施最先进的测序方法和复杂的分析技术，我们的研究将成为第一个直接探索微生物群与血管衰老的关系的研究之一。然后，将使用结合LC-MS和GC-MS技术的创新方法来进行非靶向的代谢组分析。自动化管道将用于将原始代谢组学数据处理为相对代谢物浓度的操作矩阵。先进的多变量方法将用于测试单个代谢产物的关联和与血管衰老的总代谢组谱。由于我们将使用先前收集的血浆样品和表型数据，因此所提出的分析非常有效。为了更好地了解将微生物组与表型联系起来的生物学途径，我们将测试微生物群是否影响单个代谢产物和代谢组谱。该分析将是第一个全面探索肠道微生物群与人血浆代谢物库的关系的人之一，除了提供外，还提供了影响心血管的生物学途径的关键信息 对CVD开发的生物学途径的重要机理洞察力，提出的研究可能有助于早期根据其微生物群和代谢组谱的CVD高风险的个体鉴定。基于这项工作，可以制定量身定制的策略来改变特定的血管衰老相关的微生物群和代谢产物，并通过降低CVD的发病率和死亡率来促进健康的衰老和寿命。疾病（CVD）进展。