Bile acid–microbiota crosstalk in hepatitis B virus infection

Author:

Wang Jiaxin1,Xu Huimin1,Liu Zixin1,Cao Yutong1,Chen Siyu1,Hou Ruifang2,Zhou Yun1ORCID,Wang Yandong3

Affiliation:

1. Key Laboratory of Receptors‐Mediated Gene Regulation, School of Basic Medical Sciences Henan University Kaifeng China

2. Hebi Key Laboratory of Liver Disease, Department of Infectious Diseases People's Hospital of Hebi, Henan University Hebi China

3. State Key Laboratory of Chemical Resource Engineering, College of Life Science and Technology Beijing University of Chemical Technology Beijing China

Abstract

AbstractHepatitis 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.

Funder

Natural Science Foundation of Henan Province

Publisher

Wiley

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