从基因的角度研究肠道菌群紊乱与NAFLD发生发展的内在规律是寻找NAFLD治疗新靶点的途径之一，影响肠道菌群遗传的关键基因都包括哪些以及具有何种特征，目前都亟待研究。本课题前期实验发现脂质代谢关键基因FGF21敲除小鼠在正常以及高脂饮食状态下肠道菌群均发生显著改变，Dubosiella newyorkensis菌属出现FGF21敲除后“消失”，推测Dubosiella newyorkensis可能是FGF21治疗NAFLD的新靶标。本课题旨在解析FGF21是否通过调控Dubosiella newyorkensis菌属在肠道菌群中的丰度发挥其治疗NAFLD的作用以及其调控的具体机制，研究结果不但能加深对FGF21在治疗NAFLD过程中调控机制的理解，且提供了一种新型筛选肠道菌群的方式方法，还能为寻找NAFLD治疗和预防的靶点提供理论依据。

Studying the internal laws between intestinal flora disturbance and the development of NAFLD from gene point of view is one of the approaches to find new therapeutic targets for NAFLD and It's urgent to uncover which key genes affect the inheritance of intestinal flora and what characteristics they have. This study begins with this point and found that the intestinal flora of the FGF21 knock-out mice significantly changed compared with that of the wild type mice in normal and high fat diet. The newly identified genus Dubosiella newyorkensis showed "disappeared" in FGF21 knockout mice, suggesting that Dubosiella newyorkensis may be a new target of FGF21 in the treatment of NAFLD. This project will focus on the regulatory effect of FGF21 on intestinal flora homeostasis and will further clarify the causal relationship between FGF21 and Dubosiella newyorkensis. In addition, we will deeply study the role of Dubosiella newyorkensis in the development of NAFLD and the specific mechanism of FGF21 in regulating the abundance of Dubosiella newyorkensis. This study not only deepens the understanding of the regulatory mechanism of FGF21 in the treatment of NAFLD, but also provides a new method for screening intestinal flora , and develops the theoretical basis for finding therapeutic targets of NAFLD.