Weight-Loss Diet Intervention on Cardiometabolic Factors of Gut Microbiota

摘要 令人信服的证据表明，人类肠道微生物区系与肥胖和相关疾病的发生有关 心脏新陈代谢障碍。最近的研究确定了一组循环代谢物的功能 与肠道微生物区系有关。这些微生物代谢物在微生物区系宿主中扮演着“换能器”的角色 肠道-器官/组织串扰中的通讯和传感器，并影响各种异位脂肪的分布 代谢器官和组织。饮食是肠道微生物区系最重要的调节者之一；然而，没有 一项研究评估了减肥饮食可能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。在两个最长的和 关于流行的减肥饮食--减重和减重的最大对比试验，我们建议 确定与饮食长期减肥相关的新血浆微生物代谢物 干预措施。我们将检查已鉴定的微生物代谢物的血浆水平与异位脂肪的关系。 分布在肝脏、心脏、胰腺和肾脏，以及脂肪和骨骼肌组织。此外, 我们将评估血浆微生物代谢产物的变化是否调节减肥之间的关系 心脏代谢标志物的变化。此外，我们还将研究动态关联 与肥胖和心脏代谢风险相关的微生物代谢物和血浆miRNAs的变化。调查结果 我们的研究将极大地促进肥胖症新预防和治疗策略的开发 以及相关的心脏新陈代谢障碍。

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.