慢性乙型肝炎以及肝硬化患者肠道微生物研究

目的：探讨慢性乙型肝炎以及肝硬化患者的肠道菌群变化及其与细胞因子、肝功能之间的关系。方法选取30例健康志愿者、50例肝炎后肝硬化患者以及50例慢性乙型肝炎患者,采用实时荧光定量 PCR 法检测粪便中九种肠道菌群含量,比较三组间肠道菌群变化；同时采用 ELISA 法检测慢性乙型肝炎患者血清中细胞因子如白介素-17A(IL-17)、白介素-1β( IL-1β)、白介素-6( IL-6)、干扰素-α( INF-α)、CXC 趋化因子(CXCL-13)的浓度,分析肠道菌群与细胞因子以及肝功能之间的关系。结果与健康对照组相比,慢性乙型肝炎以及肝硬化患者体内的双歧杆菌、乳酸杆菌、拟杆菌属以及瘤胃球菌属含量减少；肠杆菌科细菌、肠球菌、梭菌属、白色念珠菌以及普雷沃氏菌含量明显增加。慢性乙型肝炎患者体内的肠杆菌科细菌与凝血酶原时间(PT)呈正相关性,肠球菌与谷丙转氨酶(ALT)、谷草转氨酶(AST)呈正相关性；双歧杆菌与 AST、碱性磷酸酶(AKP)以及 HBV DNA水平呈负相关性,普雷沃氏菌属与 AST、AKP 以及 PT 呈负相关性,拟杆菌属与 AST 和 PT 呈负相关性,瘤胃球菌属与白蛋白(ALB)呈负相关性。另外,9种肠道菌群中只有肠球菌与 IL-17A 呈正相关性。结论慢性乙型肝炎以及肝硬化患者体内存在不同程度的肠道菌群失调,其中乙肝患者体内过度繁殖的肠球菌与 IL-17A 协同参与肝脏炎症反应过程,以致于肝功能受损呈恶性循环状态。

Changes of intestinal microbiota in patients with chronic hepatitis B and liver cirrhosis

Objective To investigate changes of intestinal flora and correlation with cytokines and liver function in patients with chronic hepatitis B and liver cirrhosis. Methods 30 healthy subjects, 50 patients with chronic hepa-titis B and 50 patients with cirrhosis were selected. Nine kinds of intestinall flora were quantified by FQ-PCR to compare the changes among three groups. Then the IL-17A, IL-1β, IL-6, IFN-α, CXCL-13 concentrations in the serum of patients with chronic hepatitis B were measured with ELISA to explore the relationship between intestinal flora and cytokines, liver function. Results The numbers of Bifidobacterium, Lactobacillus, Bacteroides and Rumi-nococcus were significantly decreased in patients with chronic hepatitis B and liver cirrhosis compared with healthy controls, while the numbers of Enterobacteriaceae, Enterococcus, Clostridium, Candida albicans and Prevotella were significantly increased. Positive correlations were found between Enterobacteriaceae and PT, as well as Enterococcus and ALT, AST in patients with chronic hepatitis B. Bifidobacterium was negatively linked to AST, AKP, HBV DNA. Prevotella was negatively linked to AST, AKP, PT. There was a negative correlation between Ruminococcus and ALB, as well as Bacteroides and AST, PT. In addition, Enterococcus was positively linked to IL-17A. Conclu-sion Varying degrees of intestinal flora imbalance exists in patients with chronic hepatitis B and liver cirrhosis. The overgrowth of Enterococcus acts synergistically with IL-17A to induce liver inflammation and result in impaired liver function.