肠肝轴：从临床患者分离的肠道致病菌株Escherichia coli NF73-1对非酒精性脂肪性肝病的作用及机制研究

研究表明肠道微生态（尤其肠道菌群）改变参与了非酒精性脂肪肝（NAFLD）的发生和发展，但目前研究大多局限于门及属水平。对于肠道特定、致病菌株的研究仍然匮乏。寻找与NAFLD相关的关键致病菌株是亟待解决的重要问题。我们从一名非酒精性脂肪性肝炎（NASH）患者肠黏膜中分离出大肠杆菌菌株，通过前期研究筛选出致病性最强且丰度最高的致病菌株Escherichia coli NF73-1，并进行基因组测序发现其存在重要的致病因素——VI型分泌系统（T6SS）。本研究着重探讨NF73-1如何通过破坏肠黏膜屏障功能、引起肝脏炎症反应从而加重NAFLD进展；是否可以直接对肝细胞造成损伤；深入研究NF73-1是否通过T6SS功能参与NAFLD的发生发展。该研究为将来明确特定致病菌株用于临床协助诊断及预测NAFLD的疾病活动程度提供了重要的线索，并为通过靶向干预致病菌株治疗NAFLD提供了坚实的依据。

Gut microbiota is involved in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). However, current researches are limited to phylum and species level. Few research focus on the clinically isolated pathogenic bacterial strains. It is vital to find specific pathogenic strains which is involved in NAFLD. So we isolated Escherichia coli strains from a patient with nonalcoholic steatohepatitis and then identified the most pathogenic strain with the most abundancy Escherichia coli NF73-1. Whole genome sequence indicated components of Type VI Secretion System (T6SS) in genetic annotations. Our research will focus on how NF73-1 disrupts intestinal barrier function, facilitates hepatic inflammatory responses, and aggravates NAFLD. Besides, we will also study how NF73-1 directly cause inflammatory responses to hepatocytes. Furthermore, we will explore how NF73-1 contributes to NAFLD through T6SS function. Our research will provide important clues to identify specific pathogenic strain that will assist in diagnosis and prediction for disease activity score of NAFLD. Besides, evidence is also provided for therapies targeting pathogenic bacterial strain upon our research.