Weight-Loss Diet Intervention on Cardiometabolic Factors of Gut Microbiota

摘要 令人信服的证据表明，人类肠道微生物群与肥胖及相关疾病的发展有关。 心脏代谢疾病。最近的研究确定了一组循环代谢物， 与肠道菌群有关。这些微生物代谢物在微生物宿主中充当“换能器” 通信和'传感器'在肠道器官/组织串扰，并影响异位脂肪分布在各种 代谢器官和组织。饮食是肠道微生物群最重要的调节剂之一;然而， 一项研究评估了减肥饮食如何影响新发现的微生物的长期变化。 代谢物。拟议的系统研究旨在填补这一重大研究空白。在两个最长的， 最大的比较试验流行的减肥饮食-磅损失和中央，我们建议， 鉴定与响应饮食长期体重减轻相关的新的血浆微生物代谢物 干预措施。我们将研究已鉴定的微生物代谢产物和异位脂肪的血浆水平之间的关系 分布在肝脏、心脏、胰腺和肾脏以及脂肪和骨骼肌组织中。此外，本发明还提供了一种方法， 我们将评估血浆微生物代谢物的变化是否介导了体重减轻与 以及心脏代谢标志物的变化。此外，我们还将研究 微生物代谢物和血浆miRNAs的变化与肥胖和心脏代谢风险有关。这些发现 我们的研究将大大促进肥胖症新的预防和治疗策略的发展 和相关的心脏代谢紊乱。

Abstract Compelling evidence has implicated human gut microbiota in development of obesity and related cardiometabolic disorders. Recent studies identified a group of circulating metabolites that are functionally related to gut microbiota. These microbial metabolites act as ‘transducers’ in the microbiota-host communications and ‘sensors’ in gut-organ/tissue crosstalk, and affect ectopic fat distribution in various metabolic organs and tissues. Diet is among the most important regulators of gut microbiota; however, no study has assessed how weight-loss diets may affect the long-term changes of the newly identified microbial metabolites. The proposed systems study aims to fill this significant research gap. In two of the longest and largest comparator trials on the popular weight-loss diets - POUNDS LOST and CENTRAL, we propose to identify novel plasma microbial metabolites associated with long-term weight loss in response to diet interventions. We will examine relations of plasma levels of identified microbial metabolites and ectopic fat distribution in the liver, heart, pancreas, and kidney, as well as adipose and skeletal muscle tissues. In addition, we will assess whether changes in plasma microbial metabolites mediate the relations between weight loss and changes in cardiometabolic markers. Moreover, we will examine the dynamic associations between microbial metabolites and changes in plasma miRNAs related to obesity and cardiometabolic risk. The findings from our study will considerably improve development of novel prevention and treatment strategies for obesity and related cardiometabolic disorders.