Calorie restriction (CR) has been widely recognized for its effect in reducing body weight and alleviating diabetes in humans, as well as prolonging life span in animal studies. Gut microbiome shifts contribute to part of the effects of CR, but little is known regarding their influences except on metabolism and immunity. Here we monitored gut microbiome using metagenomics and metatranscriptomics in obese individuals undergoing CR, and revealed microbial determinants that could contribute to successful weight loss. Microbiome changes are linked to changes in blood metabolome and hormones, which eventually correlate to brain functional changes as studied using functional magnetic resonance imaging (fMRI). Brain functional shifts indicate response of central neural system (CNS) to CR, and microbiome constitutes the keystone of gut-brain axis. Animal experiment further reaffirms the gut microbiome changes, metabolic and hormonal shifts of CR, while proteomic analysis of brain tissues suggest that epigenetic modifications of key proteins could explain responses of CNS to CR. Our study establishes linkage between CR, gut microbiome, metabolome/ hormones and CNS function, and demonstrates that CR has multi-facet, coordinated effects on the host, of which many could contribute to weight loss and other beneficial effects.

中文翻译：

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肠道微生物组在热量限制期间结合肠道和大脑治疗肥胖

卡路里限制（CR）在减轻体重和减轻人类糖尿病以及延长动物研究寿命方面的作用已被广泛认可。肠道微生物组的改变是造成部分CR的原因，但是除了影响新陈代谢和免疫力之外，人们对它们的影响知之甚少。在这里，我们使用宏基因组学和超转录组学方法对正在经历CR的肥胖个体监测肠道微生物组，并揭示了可能有助于成功减肥的微生物决定因素。微生物组的变化与血液代谢组和激素的变化有关，而血液代谢组和激素的变化最终与使用功能磁共振成像（fMRI）研究的脑功能变化相关。脑功能变化表明中枢神经系统（CNS）对CR的反应，而微生物组则构成了肠脑轴的基石。动物实验进一步证实了肠道微生物组的变化，CR的代谢和激素变化，而脑组织的蛋白质组学分析表明关键蛋白质的表观遗传修饰可以解释中枢神经系统对CR的反应。我们的研究建立了CR，肠道微生物组，代谢组/激素与中枢神经系统功能之间的联系，并证明CR对宿主具有多方面的协同作用，其中许多可能有助于减肥和其他有益作用。