Associations between Gut Microbiota, Plasma Metabolites, and Metabolic Syndrome Traits

肠道微生物群、血浆代谢物和代谢综合征特征之间的关联

• 批准号: 10464817
• 负责人: Sahereh Mirzaei
• 金额: $ 6.76万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-01 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10464817
• 关键词: 16S ribosomal RNA sequencing; Animals; Autoimmune Diseases; Bioinformatics; Blood Circulation; Cardiac; Cardiovascular Diseases; Cardiovascular system; Central obesity; Cerebrovascular Disorders; Choline; Clinical; Complex; Coronary Arteriosclerosis; Coronary Artery Bypass; Data; Data Analyses; Development; Diabetes Mellitus; Diagnosis; Disease susceptibility; Dyslipidemias; Environmental Risk Factor; Etiology; Event; Factor Analysis; Finland; General Population; Genetic; Genotype; Germ-Free; Goals; Heart Diseases; Heart failure; High Density Lipoproteins; Hyperglycemia; Hypertension; Individual; Insulin Resistance; Intervention; Knowledge; Laboratories; Lasso; Lead; Life; Link; Liquid Chromatography; Liver; Malignant Neoplasms; Mentors; Metabolic; Metabolic Diseases; Metabolic syndrome; Microbe; Modeling; Molecular Biology; Morbidity - disease rate; Mus; Myocardial Infarction; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Operative Surgical Procedures; Oxides; Parents; Phenotype; Plasma; Population; Population Registers; Prevention approach; Prevention strategy; Primary Prevention; Principal Investigator; Research; Risk; Risk Factors; Risk Reduction; Role; Sampling; Secondary Prevention; Shotgun Sequencing; Statistical Methods; Stroke; Structure; Survival Analysis; System; Training; Triglycerides; World Health; acute coronary syndrome; adverse outcome; aged; biomarker discovery; cardiogenesis; cardiovascular risk factor; cohort; experimental study; follow-up; global health; gut microbes; gut microbiome; gut microbiota; hazard; health economics; high risk; host microbiome; longitudinal analysis; men; metabolomics; microbial; microbiome; microbiota; microbiota metabolites; mortality; mortality risk; non-alcoholic fatty liver disease; non-genetic; novel therapeutic intervention; patient oriented; patient population; percutaneous coronary intervention; population based; predictive modeling; preventive intervention; secondary analysis; stable isotope; stool sample; tandem mass spectrometry; trait; trimethylamine; trimethyloxamine

PROJECT SUMMARY The goal of this proposal is to understand the relationship between the gut microbiome, gut derived metabolites, and metabolic syndrome traits. Metabolic syndrome is a cluster of risk factors including central obesity, dyslipidemia, hypertension, and insulin resistance with a range of secondary sequelae such as cardiovascular disease (CVD), cerebrovascular disease, and diabetes. Metabolic syndrome has been identified as one of the greatest world health challenges of the 21st century. There are emerging data that the gut microbiota have an important role for the development of metabolic syndrome and directly influences host phenotypes. A detailed understanding of the factors underlying metabolic syndrome will be useful in developing effective prevention strategies and appropriate intervention strategies for at risk individuals. In order to better understand the relationship between the gut microbiome and metabolic syndrome traits, we will perform a secondary analysis of data from the Metabolic Syndrome in Men (METSIM) study. This is a population-based cohort of 10,197 men aged 45-73 years, randomly selected from the population register of Kuopio, Eastern Finland, from 2005 to 2010. This population has been uniquely characterized for cardiovascular clinical traits such as coronary artery disease, stroke, heart failure, and metabolic syndrome traits. This proposal extends the impact of the parent study, which aimed to investigate nongenetic and genetic factors associated with metabolic syndrome and CVD in both cross sectional and longitudinal analysis. We will analyze a subset of approximately 1000 subjects who participated in a 7-year follow-up. Our hypothesis is that gut microbes contribute to metabolic syndrome traits in part through their metabolites and their metabolites are associated with major cardiovascular events. We will first determine the gut derived metabolites that have association with metabolic syndrome traits. Once we identify the subset of metabolites, we will identify individual and clusters of microbes that may influence the levels of certain plasma metabolites. We will also determine the association of plasma concentrations of the gut microbe-generated metabolite with major adverse cardiovascular events. Data will be analyzed using Lasso regression, latent class analysis, path analysis, and Cox proportional hazards regression. Results from this project will inform research on developing patient-centered prevention strategies and interventions. Understanding of the host-microbiome inter- relationships may result in novel therapeutic approaches for prevention, diagnosis, and treatment of metabolic disorders.

项目摘要 这项提案的目标是了解肠道微生物组、肠道衍生物和肠道微生物之间的关系。 代谢物和代谢综合征特征。代谢综合征是一组危险因素， 肥胖、血脂异常、高血压和胰岛素抵抗，并伴有一系列继发性后遗症， 心血管疾病（CVD）、脑血管疾病和糖尿病。代谢综合征已被确定为 是世纪最大的世界卫生挑战之一。有新的数据表明， 微生物群在代谢综合征的发展中起重要作用，并直接影响宿主 表型详细了解代谢综合征的潜在因素将有助于 为高危人士制订有效的预防策略和适当的介入策略。为了 为了更好地了解肠道微生物组与代谢综合征特征之间的关系，我们将 对男性代谢综合征（METSIM）研究的数据进行二次分析。这是一 10，197名年龄在45-73岁之间的男性，随机从人口登记册中选择， 库奥皮奥，芬兰东部，2005年至2010年。这一群体的独特特征是， 心血管临床特征，如冠状动脉疾病、中风、心力衰竭和代谢综合征 性状该提案扩展了母研究的影响，该研究旨在研究非遗传和遗传 代谢综合征和心血管疾病的相关因素的横向和纵向分析。我们将 分析参与7年随访的约1000名受试者的子集。我们的假设是 肠道微生物部分通过其代谢物导致代谢综合征特征， 与主要心血管事件相关。我们将首先确定肠道衍生的代谢物， 与代谢综合征特征的关系。一旦我们确定了代谢物的子集，我们将确定 可能影响某些血浆代谢物水平的微生物个体和簇。我们还将 确定肠道微生物产生的代谢物的血浆浓度与主要代谢物的相关性， 不良心血管事件。将使用Lasso回归、潜在类别分析、路径分析和回归分析对数据进行分析。 分析和考克斯比例风险回归。该项目的结果将为开发研究提供信息 以病人为中心的预防战略和干预措施。对宿主微生物组的理解 这种关系可能会导致新的治疗方法，用于预防，诊断和治疗代谢性疾病。 紊乱