大量研究表明，节食可以通过减少炎性因子产生，来改善代谢稳态、延长寿命，但是能够作为节食的直接作用靶点，参与调节炎症反应的中介因子仍然不清楚。我们的前期工作表明，长期节食可以优化肠道菌群结构、减少内毒素入血，从而可能成为减轻炎性衰老的一个关键因素。本研究将通过菌群移植，评价节食改变的菌群对改善炎症、减轻代谢综合征从而延缓衰老的贡献；建立长期CR模型，通过菌群的元基因组学和宿主组织的转录组学数据的关联分析，寻找对改善宿主炎症反应和代谢稳态有贡献的关键肠道菌群成员及其重要基因；分离功能菌，在无菌动物中建立研究其与宿主的分子互作机制的模型，逐步揭示节食以菌群为中介的抗衰老作用机制，不仅完善对衰老机制的理解，而且可以为人群中建立和开展以使肠道菌群结构更加平衡及减少细菌产生的抗原总量为靶点的膳食干预提供理论依据，为延缓衰老、减少代谢性失调相关疾病的发病率提供新思路和新手段。

A low-grade, systemic, chronic inflammatory condition associated with obesity has been recognized as a crucial pathological process underlying metabolic deteriorations and accelerated aging (inflammaging). The health-promoting and lifespan-extending effects of calorie restriction have been demonstrated in many mammals including non-human primates and humans. Compelling evidence points to that CR may exert its beneficial actions through attenuating the inflammatory state associated with aging and age-related diseases, but the primary mediator through which CR directly alleviate inflammation remains unclear. Our previous publication showed that CR can significantly modulate gut microbiota and reduce endotoxin load in host serum, indicating that CR modulated gut microbiota may play a critical role in reducing inflammation and extending lifespan of the hosts. In this study, gut microbiota transplantation to germfree mice will be employed to evaluate the causative role of gut microbiota in CR mediated health benefits; Co-variation analysis between metagenomic data of the CR modulated gut microbiota and host transcriptomic data will be used to identify those key functional bacteria and their important genes; these functional bacteria will be isolated and inoculated into germfree mice to establish gnotobiotic model for further mechanistic studies. This project will generate new insights on anti-aging effects of CR and may shed light on how nutritional intervention for human beings should be formulated to target gut microbiota related inflammation and metabolic deterioration.