Weight-Loss Diet Intervention on Cardiometabolic Factors of Gut Microbiota

描述（由申请人提供）：肠道微生物群最近已成为一种新的代谢活性“器官”，与肥胖症和相关代谢紊乱（如糖尿病和心血管疾病）密切相关;令人信服的证据表明，与肠道微生物群代谢相关的几种关键代谢物（TMAO、L-肉碱、胆汁酸亚型）可能在介导代谢效应中发挥关键作用。饮食是塑造肠道微生物群的主要力量，减肥可能会改变肠道微生物群的代谢。本申请的目的是检查大量营养素（脂肪、蛋白质和碳水化合物）不同的减肥饮食对811名超重或肥胖患者肠道微生物群代谢中涉及的新型心脏代谢产物的长期（2年）影响，这些患者来自迄今为止关于流行减肥饮食的最大和最全面的比较试验之一-POUNDS LOST试验。我们还将评估血浆肠道微生物群代谢物变化与能量摄入和消耗标志物变化的关系，包括肠道激素（GLP-1，ghrelin），静息代谢率（RMR）和通过双标记水（DLW）测量的总能量消耗（TEE）;以及代谢风险因素的变化，包括胰岛素敏感性，脂质，脂肪因子，炎症和氨基酸。此外，我们将研究肠道微生物群代谢产物与全球脂肪基因表达之间的关联。由于能量平衡和代谢标志物的测量以及脂肪基因表达是通过单独的赠款资助的，因此拟议的项目将以极具成本效益的方式进行。我们已经召集了一批经验丰富的合作者，他们在流行病学，代谢组学，基因表达，统计学，临床试验和营养学方面具有专业知识。我们相信，该项目的发现将为肠道代谢效应提供新的见解， 微生物群及其与饮食因素的关系;并通过饮食干预大大有助于推进肥胖和相关代谢紊乱的新预防和治疗策略。

DESCRIPTION (provided by applicant): Gut microbiota has recently emerged as a novel, metabolically active 'organ', tightly linked to obesity and related metabolic disorders such as diabetes and cardiovascular disease; and compelling evidence indicates that several key metabolites (TMAO, L-carnitine, bile acids subtypes) related to gut microbiota metabolism may play pivotal roles in mediating the metabolic effects. Diet is a major force that shapes gut microbiota and weight loss may alter metabolism of gut microbiota. The goal of this application is to examine the long-term (2 years) effects of weight-loss diets varying in macronutrients (fat, protein, and carbohydrate) on the novel cardiometabolic metabolites involved in gut microbiota metabolism in 811 overweight or obese patients from thus far one of the largest and most comprehensive comparator trials on the popular weight-loss diets - the POUNDS LOST trial. We will also assess the relation of changes in plasma gut microbiota metabolites with changes in markers of energy intake and expenditure, including gut hormones (GLP-1, ghrelin), resting metabolic rate (RMR), and total energy expenditure (TEE) measured by doubly-labeled water (DLW); as well as with changes in metabolic risk factors including insulin sensitivity, lipids, adipokines, inflammation, and amino acids. In addition, we will examine the associations between gut microbiota metabolites and global adipose gene expression. Because measurement of energy balance and metabolic markers, and adipose gene expression are funded through separate grants, the proposed project will be conducted in an extremely cost-efficient manner. We have assembled a solid group of experienced collaborators with expertise in epidemiology, metabolomics, gene expression, statistics, clinical trial, and nutrition. We believe that findings of this project will provide novel insights into the metabolic effects of gut microbiota and their relations with dietary factors; and considerably contribute to advance toward new prevention and treatment strategies for obesity and related metabolic disorders through diet intervention.