肠道微生物菌群与HBV感染不同临床结局的关系研究

Chronic hepatitis B, cirrhosis and hepatocellular carcinoma induced by HBV infection severely harm people’s health and social development. Illustrating the root cause of the different clinical outcomes of HBV infection is the key prevention and treatment of HBV infection. Some studies have indicated that liver is closely related to gut in the aspect of anatomy and pathophysiology, resulting in the interaction between the intestinal flora and liver diseases. However, the relationship between gut microbiota and different clinical outcomes of HBV infection still remains unclear. Our previous preliminary experiment had shown the different features of gut microbiota had certain association with different clinical outcomes of HBV infection. Therefore, we propose the hypothesis that a relationship exists between gut microbiota and different clinical outcomes of HBV infection. In order to verify this hypothesis, we will explore further about the features of gut microbiota carried by those who has developed different clinical outcomes of HBV infection, by performing next-generation sequencing, collecting the patients’ clinical information, applying relevant prediction model and statistical analysis method. This study would reveal the causes and the stimulants of HBV infection’s clinical outcomes in terms of microbiology, thus to provide theoretical basis for early warning of different clinical outcomes of HBV infection.

HBV感染及其发展成的慢性乙型肝炎、肝硬化和肝癌严重危害人民健康和社会发展。系统阐明HBV感染不同临床结局的根本原因是防治这一问题的关键。肝肠在解剖位置和生理病理功能密切相关，肠道微生物与肝脏疾病互相影响。但肠道微生物与HBV感染不同临床结局的关系未明。我们前期的预实验提示不同肠道微生物的结构特征与不同HBV感染临床结局有一定的关系。为此，我们提出“肠道微生物菌群与HBV感染不同临床结局存在关系”的假说。为了验证这一假说，我们将采用二代测序，结合患者临床信息，并通过相关的预测模型、统计分析方法深入探讨HBV感染不同临床结局患者肠道微生物的结构特征，以期从微生物的角度揭示HBV感染临床结局的原因和促进因素，为不同HBV感染结局的早期预警提供理论基础。

HBV感染及其发展成的慢性乙型肝炎、肝硬化和肝癌严重危害人民健康和社会发展。肝、肠在解剖位置和生理病理功能密切相关，肠道微生物与肝脏疾病互相影响。本研究探讨了肠道微生物与HBV感染不同临床结局的关系。本研究采用16S rDNA测序技术分析了健康人群以及HBV 感染不同发展阶段【包括慢性乙型肝炎组（CHB）、乙肝相关性肝硬化组（LC）及乙肝相关性肝癌组（HCC）】患者中肠道微生物菌群丰度和结构变化，揭示了HBV相关性肝病（HBVCLD）不同发展阶段肠道菌群的结构特征。结果发现与健康人群相比，Prevotella、Atopobium、Veillonella、Alistipes在CHB患者中显著升高；Akkermansia、Atopobium、Prevotella、Parabacteroides在LC患者中显著升高；Veillonella、Phenylobacterium、Synechococcus 在HCC患者中显著升高；与健康人群相比，HBV感染相关肝脏疾病患者（包括CHB、LC、HCC）的菌群代谢功能发生变化。同时，我们揭示了健康人群、CHB、LC、HCC的核心菌群及其特有的菌群。另外，我们还获得不同菌属在环境样本中的共存关系，并得到其在同一环境下的相互作用情况。.本研究可为HBV感染不同转归预测提供候选新的标志物和治疗靶标，并为不同HBV感染结局的早期预警提供理论基础。