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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要该提案的目标是了解肠道微生物组、肠道衍生的微生物组之间的关系代谢物和代谢综合征特征。代谢综合征是一系列危险因素，包括中枢性肥胖、血脂异常、高血压和胰岛素抵抗以及一系列继发性后遗症，例如心血管疾病（CVD）、脑血管疾病和糖尿病。代谢综合征已被确定是 21 世纪世界最大的健康挑战之一。有新出现的数据表明肠道微生物群对代谢综合征的发生具有重要作用，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群制定有效的预防策略和适当的干预策略。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。这是一个以人口为基础的队列，由 10,197 名 45-73 岁男性组成，随机选自人口登记册芬兰东部库奥皮奥，2005 年至 2010 年。该人群具有独特的特征心血管临床特征，如冠状动脉疾病、中风、心力衰竭和代谢综合征特征。该提案扩大了母研究的影响，该研究旨在研究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。我们将分析了参与 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部分通过其代谢物导致代谢综合征特征，并且其代谢物是与主要心血管事件有关。我们将首先确定肠道衍生的代谢物与代谢综合征特征的关联。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微生物群。我们也会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。将使用 Lasso 回归、潜在类分析、路径分析数据分析和 Cox 比例风险回归。该项目的结果将为开发研究提供信息以患者为中心的预防策略和干预措施。了解宿主-微生物组之间的关系关系可能会产生预防、诊断和治疗代谢性疾病的新治疗方法失调。