肠道菌群-胆汁酸-肝脏FXR轴介导老年NAFLD发生及花色苷防治作用研究

年龄是非酒精性脂肪肝（NAFLD）的一个重要的独立危险因素。然而年老促进NAFLD发生、发展的机制仍不明确。我们前期研究发现老年小鼠肠道菌群组分和胆汁酸代谢物与年轻小鼠具有明显的差别，以及膳食花色苷具有明显改善NAFLD的作用，因而提出“肠道菌群-胆汁酸-肝脏FXR”轴的失调是否为老年NAFLD发生的重要途径？花色苷是否通过改善这一途径而抑制老年NAFLD的发生和发展？本项目拟建立生命周期小鼠队列，通过肠道菌群测序及靶向代谢检测观察生命周期中，肠道菌群、胆汁酸代谢物与NAFLD的关联；通过粪菌移植等技术阐明肠道菌群变化经调节胆汁酸-肝脏FXR途径促进老年NAFLD发生的新机制，并明确花色苷改善老年肠道菌群组分，肠道胆汁酸代谢物，继而抑制老年NAFLD发生的机制。本研究对揭示老年NAFLD发生和发展的肠道微生态机制，以及膳食花色苷改善老年NAFLD具有重要的科学和实践指导意义。

Age is an important independent risk factor for the nonalcoholic fatty liver disease (NAFLD). However, the mechanism of aging in the progression of NAFLD is still unclear. Our previous study found that the intestinal microbiota and bile acids composition of aging mice were significantly different from those of young mice, and dietary anthocyanins could improve NAFLD progression. Therefore, here we propose that the imbalance of "intestinal microbiota-bile acids-liver FXR" axis is an important target for age-related NAFLD and anthocyanin can inhibit the development of NAFLD in the aging mice. Firstly, we will establish the aging mice cohort to observe the association between intestinal microbiota, bile acids and NAFLD in aging. Next, fecal bacteria transplantation will be used to clarify the mechanism of intestinal microbiota in the progression of NAFLD in the aging by regulating “bile acids-liver FXR” pathway. Finally, anthocyanins will be tested whether it can improve intestinal microbiota and bile acids dysregulation to ameliorate the age-related NAFLD. To conclude, this study will reveal the mechanism of the development of NAFLD in the aging. Furthermore, this study will also provide the nutritional method to improve age-related NAFLD.