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: 10581501
• 负责人: Sahereh Mirzaei
• 金额: $ 7.18万
• 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/10581501
• 关键词: 16S ribosomal RNA sequencing; Animals; Autoimmune Diseases; Bioinformatics; Cardiac; Cardiovascular Diseases; Cardiovascular system; Central obesity; Cerebrovascular Disorders; Choline; Circulation; Clinical; Collaborations; Complex; Coronary Arteriosclerosis; Coronary Artery Bypass; Cross-Sectional Studies; Data; Data Analyses; Development; Diabetes Mellitus; Diagnosis; Disease susceptibility; Dyslipidemias; Economics; 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; 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; Parents; Phenotype; Plasma; Population; Population Registers; Prevention approach; Prevention strategy; Primary Prevention; Principal Investigator; Random Allocation; Research; Risk; Risk Factors; Risk Reduction; Role; Sampling; Secondary Prevention; Shotgun Sequencing; Statistical Methods; Stroke; Structure; Survival Analysis; System; Training; Triglycerides; World Health; absorption; acute coronary syndrome; adverse outcome; aged; biomarker discovery; cardiovascular risk factor; cohort; experimental study; follow-up; global health; gut microbes; gut microbiome; gut microbiota; hazard; 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.

项目总结 这项建议的目标是了解肠道微生物群、肠道衍生的 代谢物和代谢综合征的特征。代谢综合征是一组风险因素，包括中枢 肥胖、血脂异常、高血压和胰岛素抵抗，并有一系列继发性后遗症，如 心血管疾病(CVD)、脑血管疾病和糖尿病。代谢综合征已被确认 作为21世纪最大的世界卫生挑战之一。有新出现的数据表明 微生物区系在代谢综合征的发生发展中起着重要作用，并直接影响宿主 表型。对代谢综合征潜在因素的详细了解将有助于 为高危人群制定有效的预防策略和适当的干预策略。按顺序 为了更好地了解肠道微生物群和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。这是一个 以人口为基础的队列10,197名年龄在45-73岁之间的男性，随机从 2005年至2010年，芬兰东部的库奥皮奥。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 特征。这一提议扩大了父母研究的影响，该研究旨在调查非遗传和遗传 横断面和纵向分析中与代谢综合征和心血管疾病相关的因素。我们会 分析参与7年随访的大约1000名受试者的子集。我们的假设是 肠道微生物对代谢综合征特征的贡献部分是通过它们的代谢物和它们的代谢物 与重大心血管事件有关。我们将首先确定肠道衍生的代谢物 与代谢综合征特征的相关性。一旦我们确定了代谢物的子集，我们就会确定 可能影响某些血浆代谢物水平的微生物个体和群。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 不良心血管事件。数据将使用套索回归、潜在类别分析、路径分析进行分析 分析，并进行COX比例风险回归分析。该项目的结果将为开发 以患者为中心的预防策略和干预措施。对寄主-微生物组相互作用的认识 这些关系可能导致新陈代谢疾病的预防、诊断和治疗的新治疗方法 精神错乱。