Entecavir therapy reverses gut microbiota dysbiosis induced by hepatitis B virus infection in a mouse model
Entecavir therapy reverses gut microbiota dysbiosis induced by hepatitis B virus infection in a mouse model
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恩替卡韦治疗可逆转小鼠模型中乙型肝炎病毒感染引起的肠道微生物群失调
DOI：
10.1016/j.ijantimicag.2020.106000
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发表时间：
2020-07-01
影响因子：
10.8
通讯作者：
Hong, Bin
中科院分区：
文献类型：
--
作者：
Li, Xingxing;Wu, Shuo;Hong, Bin
慢性B型肝炎病毒（HBV）感染是一个全球性的公共卫生问题。肠道菌群与慢性HBV感染诱导的肝脏疾病的发病机制有关。方法和结果：本研究建立了重组腺相关病毒血清型8（rAAV 8）介导的HBV持续感染小鼠模型。恩替卡韦（ETV）治疗显着降低血清和肝脏中的HBV DNA载量。使用盲肠内容物样品的16 S rDNA测序分析来进行rAAV 8-HBV感染小鼠和ETV处理小鼠与健康对照的肠道微生物群组成的比较。rAAV 8-HBV感染小鼠肠道菌群α多样性降低，ETV治疗4周后显著恢复。在rAAV 8-HBV感染的小鼠中，布劳特氏菌和严格意义上的梭菌显著减少，并且与HBsAg和HBeAg水平呈负相关。与此相反，丁酸球菌和普雷沃氏菌NK 3B 31群与HBsAg和HBeAg呈正相关。此外，还观察到已知的肠道屏障保护菌Akkermansia在rAAV 8-HBV感染小鼠中显著减少，并且在ETV治疗后恢复到健康对照的水平，而Akkermansia的丰度与血清和肝脏中的HBV DNA载量均呈负相关。综上所述，结果表明，肠道微生物群的生态失调在持续HBV感染的小鼠中发展，并被ETV治疗有效逆转，阐明肠道微生物群对HBV持续感染和抗病毒治疗的机制。(c)2020 Elsevier B. V.和国际化疗学会。All rights reserved.
Introduction: Chronic hepatitis B virus (HBV) infection is a global public health problem. The gut microbiota has been linked to pathogenesis of liver diseases induced by chronic HBV infection.Methods and Results: This study established a recombinant adeno-associated virus serotype 8 (rAAV8)mediated persistent HBV infection mouse model. Entecavir (ETV) treatment significantly decreased the HBV DNA load both in serum and the liver. The comparison of gut microbiota composition of rAAV8-HBVinfected mice and ETV-treated mice with healthy controls was carried out using 16S rDNA sequencing analysis of caecal content samples. The intestinal microbiota alpha diversity of rAAV8-HBV-infected mice decreased, and significantly restored after 4 weeks of ETV therapy. Blautia and Clostridium sensu stricto significantly decreased in rAAV8-HBV-infected mice and was negatively correlated with both HBsAg and HBeAg levels. On the contrary, the Butyricicoccus and Prevotellaceae NK3B31 groups exhibited positive correlation with HBsAg and HBeAg. Furthermore, it was observed that Akkermansia, a known gut barrierprotecting bacterium, significantly decreased in rAAV8-HBV-infected mice and was restored to the level of that in healthy controls after ETV therapy, while the abundance of Akkermansia was negatively correlated with HBV DNA load both in serum and the liver.Conclusion: Taken together, the results showed that dysbiosis of gut microbiota developed in the persistent HBV-infected mice and was effectively reversed by ETV treatment, shedding light on the mechanisms of gut microbiota on HBV-persistent infection and antiviral therapy. (c) 2020 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.