补充嗜黏蛋白阿克曼菌通过NKT细胞抑制非酒精性脂肪肝炎进展为肝癌

目前尚无预防非酒精性脂肪性肝炎（non-alcoholic steatohepatitis，NASH）进展为肝癌（hepatocellular carcinoma，HCC）的可靠手段，肠道微生物群改变在NASH进展为HCC中发挥重要作用，最新研究发现肠道原籍菌嗜黏蛋白阿克曼菌（akkermansia muciniphila，AKK）菌可预防炎癌，所以我们推断补充AKK菌可抑制NASH进展为HCC。我们的预实验结果表明，NASH和NASH-HCC患者和动物模型中肠道AKK菌丰度降低，补充AKK菌可减轻减轻NASH严重程度，体外实验发现AKK菌促进NKT细胞杀伤肝癌细胞。在预实验基础上，本项目拟在NASH-HCC连续动物模型中进一步探究补充AKK菌对NASH进展为HCC的作用，以及是否通过调节NKT细胞抑制NASH-HCC发生，为AKK益生菌应用于NASH治疗和预防其进展为HCC提供依据。

There is no reliable method to prevent the progression of nonalcoholic steatohepatitis (NASH) to hepatocellular carcinoma (HCC) at present. Recent studies have found that akkermansia muciniphila (AKK) can inhibit inflammatory cancer. Gut microbiota play a crucial role in NASH progression to HCC. thus, we speculate that recovery of AKK could prevent NASH-to-HCC progression. The abundance of intestinal AKK in NASH and NASH-HCC patients and animal models were reduced, and the administration of AKK could improve NASH severity in mice. The in vitro results showed that AKK promoted the apoptosis of hepatic carcinoma cell line by NKT cells. On the basis of preliminary experiments, we were to further explore the the whether supplementation of akkermansia muciniphila could prevent non-alcoholic steatohepatitis HCC progression by NKT cells in an animal model. This study will provide theoretical basis for the application of AKK in the treatment of NASH and prevention of its progression to HCC.