哺乳动物肝脏脂肪变性常伴有炎症和纤维化，而鹅肝脏可沉积大量脂肪而不发生明显的病理症状，提示鹅脂肪肝(或肥肝)的形成存在某种独特机制。在哺乳动物（如人和鼠）中，肠道菌群及其代谢物的紊乱可诱发脂肪肝等多种疾病。然而，肠道菌群是否参与鹅肥肝的形成尚不清楚。本课题组前期研究发现，鹅肥肝的形成伴有明显的肠道菌群结构变化。为阐明肠道菌群及其代谢物与鹅肥肝形成的关系和作用机制，本研究拟采用宏基因组学方法分析鹅肥肝形成过程中肠道菌群的结构和功能变化，通过对宿主肠道组织的转录组分析，揭示肠道在菌群参与脂肪肝形成中的介导作用，以及对肠道内容物、血液和肝脏代谢组进行分析，识别肠道菌群代谢物的指纹特征。在此基础上，利用体外细胞试验和活体试验进行部分验证，从而明确肠道菌群及其代谢物在鹅肥肝形成中的变化规律和作用机理。该项目的完成不仅有助于深入阐明鹅肥肝的形成机制，而且为人类和其他动物脂肪肝的研究提供参考。

In mammalian animals, severe hepatic steatosis is often accompanied with inflammation and fibrosis. In contrast, no overt pathological symptoms are observed in goose liver with severe steatosis, suggesting goose may host a unique mechanism underlying the development of its fatty liver. It is known that disorders in gut microbiota and their metabolites can induce several diseases including non-alcoholic fatty liver disease (NAFLD) in mammalian animals (e.g., human and mouse). However, it is unclear whether gut microbiota and their metabolites contribute to goose fatty liver. Our preliminary data indicate dramatic constitutive changes in gut microbiota in the development of goose fatty liver. To further address this, the structural and functional changes in gut microbiota will be determined by de novo metagenomics analysis in this study. Intestinal transcriptome analysis will also be performed to reveal the mediating role of intestine in the participation of gut microbiota to the formation of goose fatty liver. Moreover, the metabolites from gut content as well as hepatic and blood metabolites will be analyzed so that the fingerprint of metabolites of gut microbiota may be identified. Based on these analyses, in vitro and vivo studies will be further employed for validation, thus it may become clear whether gut microbiota and their metabolites are involved in the unique mechanism underlying goose fatty liver. The completion of this project will not only promotes the understanding of mechanism for the development of goose fatty liver, but also provides new solution to NAFLD-associated problems in human and other economic animals.