Role of Gut Microbial Metabolites in the Pathogenesis of Primary Liver Cancers

Nutrients. 2024 Jul 22;16(14):2372. doi: 10.3390/nu16142372.

Abstract

Hepatobiliary malignancies, which include hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), are the sixth most common cancers and the third leading cause of cancer-related death worldwide. Hepatic carcinogenesis is highly stimulated by chronic inflammation, defined as fibrosis deposition, and an aberrant imbalance between liver necrosis and nodular regeneration. In this context, the gut-liver axis and gut microbiota have demonstrated a critical role in the pathogenesis of HCC, as dysbiosis and altered intestinal permeability promote bacterial translocation, leading to chronic liver inflammation and tumorigenesis through several pathways. A few data exist on the role of the gut microbiota or bacteria resident in the biliary tract in the pathogenesis of CCA, and some microbial metabolites, such as choline and bile acids, seem to show an association. In this review, we analyze the impact of the gut microbiota and its metabolites on HCC and CCA development and the role of gut dysbiosis as a biomarker of hepatobiliary cancer risk and of response during anti-tumor therapy. We also discuss the future application of gut microbiota in hepatobiliary cancer management.

Keywords: cholangiocarcinoma; gut microbiota; gut–liver axis; hepatocellular carcinoma; immunotherapy; inflammation.

Publication types

  • Review

MeSH terms

  • Animals
  • Bile Acids and Salts / metabolism
  • Bile Duct Neoplasms / metabolism
  • Bile Duct Neoplasms / microbiology
  • Carcinogenesis / metabolism
  • Carcinoma, Hepatocellular* / metabolism
  • Carcinoma, Hepatocellular* / microbiology
  • Cholangiocarcinoma* / etiology
  • Cholangiocarcinoma* / metabolism
  • Cholangiocarcinoma* / microbiology
  • Dysbiosis*
  • Gastrointestinal Microbiome* / physiology
  • Humans
  • Liver / metabolism
  • Liver Neoplasms* / metabolism
  • Liver Neoplasms* / microbiology

Substances

  • Bile Acids and Salts

Grants and funding

This research received no external funding.