Key Laboratory of Receptors-Mediated Gene Regulation, School of Basic Medical Sciences, Henan University, Kaifeng, China.
Hebi Key Laboratory of Liver Disease, Department of Infectious Diseases, People's Hospital of Hebi, Henan University, Hebi, China.
J Gastroenterol Hepatol. 2024 Aug;39(8):1509-1516. doi: 10.1111/jgh.16604. Epub 2024 May 9.
Hepatitis B virus (HBV) is a hepatotropic non-cytopathic virus characterized by liver-specific gene expression. HBV infection highjacks bile acid metabolism, notably impairing bile acid uptake via sodium taurocholate cotransporting polypeptide (NTCP), which is a functional receptor for HBV entry. Concurrently, HBV infection induces changes in bile acid synthesis and the size of the bile acid pool. Conversely, bile acid facilitates HBV replication and expression through the signaling molecule farnesoid X receptor (FXR), a nuclear receptor activated by bile acid. However, in HepaRG cells and primary hepatocytes, FXR agonists suppress HBV RNA expression and the synthesis and secretion of DNA. In the gut, the size and composition of the bile acid pool significantly influence the gut microbiota. In turn, the gut microbiota impacts bile acid metabolism and innate immunity, potentially promoting HBV clearance. Thus, the bile acid-gut microbiota axis represents a complex and evolving relationship in the context of HBV infection. This review explores the interplay between bile acid and gut microbiota in HBV infection and discusses the development of HBV entry inhibitors targeting NTCP.
乙型肝炎病毒 (HBV) 是一种嗜肝性非细胞病变病毒，其特征在于肝脏特异性基因表达。HBV 感染劫持胆汁酸代谢，特别是通过胆盐输出泵 (NTCP) 损害胆汁酸摄取，NTCP 是 HBV 进入的功能性受体。同时，HBV 感染诱导胆汁酸合成和胆汁酸池大小的变化。相反，胆汁酸通过信号分子法尼醇 X 受体 (FXR) 促进 HBV 复制和表达，FXR 是一种被胆汁酸激活的核受体。然而，在 HepaRG 细胞和原代肝细胞中，FXR 激动剂抑制 HBV RNA 表达以及 DNA 的合成和分泌。在肠道中，胆汁酸池的大小和组成显著影响肠道微生物群。反过来，肠道微生物群影响胆汁酸代谢和先天免疫，可能促进 HBV 清除。因此，胆汁酸-肠道微生物群轴在 HBV 感染中代表了一种复杂且不断发展的关系。本综述探讨了 HBV 感染中胆汁酸和肠道微生物群之间的相互作用，并讨论了针对 NTCP 的 HBV 进入抑制剂的开发。
