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Role of the intestinal microbiome in liver fibrosis development and new treatment strategies

  • Rongrong Zhou
    Affiliations
    Department of Infectious Diseases, Xiangya Hospital, Central South University, and Key Laboratory of Viral Hepatitis, Changsha, Hunan, China

    Department of Medicine, University of California San Diego, La Jolla, California
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  • Xuegong Fan
    Affiliations
    Department of Infectious Diseases, Xiangya Hospital, Central South University, and Key Laboratory of Viral Hepatitis, Changsha, Hunan, China
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  • Bernd Schnabl
    Correspondence
    Reprint requests: Bernd Schnabl, Department of Medicine, University of California San Diego, 9500 Gilman Drive, MC0702, La Jolla, CA 92093.
    Affiliations
    Department of Medicine, University of California San Diego, La Jolla, California

    Department of Medicine, VA San Diego Healthcare System, San Diego, California
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Published:February 16, 2019DOI:https://doi.org/10.1016/j.trsl.2019.02.005
      Liver cirrhosis is a major cause of morbidity and mortality worldwide. The most common chronic liver diseases in western countries are alcohol-associated liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD). Although these diseases have different causes, liver fibrosis develops via shared mechanisms. The liver and intestinal microbiome are linked by the portal vein and have bidirectional interactions. Changes in the intestinal microbiome contribute to the pathogenesis and progression of liver diseases including ALD, NAFLD, viral hepatitis and cholestatic disorders, based on studies in patients and animal models. Intestinal microbial dysbiosis has been associated with liver cirrhosis and its complications. We review the mechanisms by which alterations in the microbiome contribute to liver fibrosis and discuss microbiome-based treatment approaches.

      Abbreviations:

      ALD (alcohol-associated liver disease), NAFLD (non-alcoholic fatty liver disease), HE (hepatic encephalopathy), HSCs (hepatic stellate cells), ECM (extracellular matrix), HCC (hepatocellular carcinoma), FXR (farnesoid X receptor), IL (interleukin), CCL2 (C-C motif chemokine ligand 2), TNF (tumor necrosis factor), TLRs (toll-like receptors), AH (alcoholic hepatitis), PAMPs (pathogen-associated molecular patterns), BMI (body mass index), FMT (fecal microbiome transplantation), NASH (non-alcoholic steatohepatitis), GLP (glucagon-like peptide), FGF (fibroblast growth factor), PBC (primary biliary cholangitis), PSC (primary sclerosing cholangitis), IBD (inflammatory bowel disease), UC (ulcerative colitis), OTUs (operational taxonomic units), ALP (alkaline phosphatase), UDCA (ursodeoxycholic acid), HBV (hepatitis B virus), HCV (hepatitis C virus), DAAs (direct acting agents), SVR (sustained virologic response), SBP (spontaneous bacterial peritonitis), ACLF (acute-on-chronic liver failure), MELD (model for end-stage liver disease), CDR (cirrhosis/dysbiosis ratio), ALT (alanine aminotransferase), AST (aspartate aminotransferase), GGT (gamma-glutamyl transferase), SHP (short heterodimer partner), CYP7A1 (cholesterol 7-alpha-hydroxylase), TIMP-1 (tissue inhibitor of metalloproteinase-1)
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