非酒精性脂肪肝（NAFLD）是最常见的慢性肝病，仍缺乏安全有效的治疗方式。肠道菌及其介导的胆汁酸代谢紊乱是NAFLD形成的关键机制之一。黄芪多糖是健脾益气类中药黄芪的活性部位，口服不易吸收。我们前期研究发现黄芪多糖能有效抑制高脂饮食诱导的NAFLD形成，且与其调控肠道菌有直接关系。黄芪多糖在一定程度上恢复肝脏胆汁酸稳态，调控胆汁酸合成及糖脂代谢相关基因的表达，但确切机制不清。因此我们提出“黄芪多糖通过调节高脂喂养小鼠的肠道菌组成，调节机体胆汁酸稳态及胆汁酸介导的肝脏脂质代谢通路，从而抑制NAFLD形成”的科学假说，研究黄芪多糖对肝脏胆汁酸合成及脂质代谢通路上关键靶标的调节作用，结合体内外实验明确黄芪多糖改变的肠道菌及胆汁酸对于脂质代谢及脂肪肝形成的作用。该研究将明确黄芪多糖抑制NAFLD效应与调节肠道菌介导的胆汁酸代谢的关系，揭示以黄芪多糖为代表的植物多糖对机体发挥整体性代谢调节的机理。

Non-alcoholic fatty liver disease（NAFLD）is the most common chronic liver disease. Safe and effective medications are very scare in NAFLD prevention or therapy currently. It has been well-established that the disruption of gut microbiome homeostasis and bile acids metabolism are the key mechanisms of NAFLD. Astraglus polysaccharide is the main component of Huangqi, a typical TCM with invigorating Spleen and supplementing Qi activity. Astraglus polysaccharide is nonabsorbable in gut system. Our previous experiments have demonstrated that astraglus polysaccharide is effective in preventing high-fat diet induced fatty liver disease in mice, which is directly related with its regulation on gut microbiota. Astraglus polysaccharide partially restores bile acids in liver tissue, as well as the genes involved in bile acids synthesis and lipids metabolism. However, it is unclear about the exact mechanisms underlying the preventive activity of astraglus polysaccharide against NAFLD. Based on our preliminary results, we hypothesized that astraglus polysaccharide prevented the formation of NAFLD by modulating gut microbiota and its regulated bile acids metabolism leading to the restoration of lipids metabolism in the liver. In this study, we will focus on investigating the effect of astraglus polysaccharide on the targets of bile acid synthesis and lipids metabolism, and the functions of altered gut microbiota and bile acids in affecting the lipids metabolism and the formation of NAFLD. This study will reveal the relation of the protective effect of astraglus polysaccharide on NAFLD with its regulation on gut microboita and bile acids, and shed lights on revealing the metabolisms of herb-derived polysaccharides in modulation of holistic metabolism.