肠道菌群在人和其他动物的糖脂代谢中发挥重要的调节作用。肠道细菌代谢食物所产生的小分子例如短链脂肪酸，转化胆酸所产生的信号分子次级胆酸等，以及与肠道免疫系统互作产生的免疫反应等，都经过一个被称为“肠-肝轴”的体内体系进入肝脏从而实现对糖脂代谢的调控。但在肠道菌群的作用研究不断深入的同时，肠-肝轴的具体途径却主要停留在较为传统的认识上，即肝门静脉是主要的肝-肠轴作用途径；与此同时，并行的淋巴循环系统所具有的巨大转运潜力和免疫功能却在这个重要系统中被忽视。因此，在该项目中我们猜想，肠-肝轴其实是两个路径共同发挥作用。首先我们在体内条件下研究在不同的细菌代谢和免疫的情况下，两个循环系统中各自所转运的代谢产物的不同，以及重要的免疫细胞和因子的差异；在体外我们利用类器官和细胞培养，建立肠-肝轴的模拟系统，然后在加入循环系统特异性的免疫细胞或者因子的情况下，单独研究某个循环系统的功能及对糖脂代谢的影响。

Gut microbiome plays essential role in carbohydrate and lipid metabolism in human and other animals. Microbial metabolites including short-chain fatty acids, secondary bile acids transformed from bile acids, as well as activated immune cells and cytokines induced by gut microbes all contribute to modulation of carbohydrate and lipid metabolism in the liver, via a regulatory route termed “gut-liver axis”. However, while the knowledge into microbiome is developing quickly, the exact route of action of gut-liver axis is yet understudied, for that the traditional wisdom acknowledges hepatic portal vein as the main delivery route for metabolites etc. The parallel lymph system is gaining recognition for its transport potential, immune capacity and important roles in many metabolic diseases, and we hypothesize that it also act as one major part of gut-liver axis. Here in this project, we thus test the idea that gut-liver acts via two routes, using both in vivo and in vitro experiments. In mouse models we use different diet, bacterial strains to simulate several metabolic and immune conditions, to study the quantitative and qualitative differences of the two circulation systems and consequences in modulating carbohydrate and lipid metabolism. Using organoids cultured from the intestine and liver cell culture, we simulate the gut-liver axis and by adding specific immune cells/cytokines/metabolites identified from the in vivo study, we aim to establish the functions of a single circulation system and its impact on carbohydrate and lipid metabolism, a test that is extremely difficult in vivo.