The gut microbiome and liver cancer: mechanisms and clinical translation

Key Points

  • Intestinal dysbiosis and increased bacterial translocation contribute to the pathophysiology of chronic liver disease (CLD) and hepatocarcinogenesis

  • A large body of literature has demonstrated that targeting the gut-microbiota–liver axis can inhibit the development of hepatocellular carcinoma (HCC) in mice and rats

  • Promising findings from these preclinical studies in mice and rats have not yet been translated to clinical settings, presenting therapeutic opportunities

  • Targeting the gut–liver axis by nonabsorbable antibiotics such as rifaximin might not only prevent the development of HCC in patients with CLD, but additionally reduce other complications and improve survival

Abstract

Hepatocellular carcinoma (HCC) is the third leading cause of worldwide cancer mortality. HCC almost exclusively develops in patients with chronic liver disease, driven by a vicious cycle of liver injury, inflammation and regeneration that typically spans decades. Increasing evidence points towards a key role of the bacterial microbiome in promoting the progression of liver disease and the development of HCC. Here, we will review mechanisms by which the gut microbiota promotes hepatocarcinogenesis, focusing on the leaky gut, bacterial dysbiosis, microbe-associated molecular patterns and bacterial metabolites as key pathways that drive cancer-promoting liver inflammation, fibrosis and genotoxicity. On the basis of accumulating evidence from preclinical studies, we propose the intestinal-microbiota–liver axis as a promising target for the simultaneous prevention of chronic liver disease progression and HCC development in patients with advanced liver disease. We will review in detail therapeutic modalities and discuss clinical settings in which targeting the gut-microbiota–liver axis for the prevention of disease progression and HCC development seems promising.

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Figure 1: Contribution of the gut microbiota to hepatocarcinogenesis: mechanisms and therapeutic targets.

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Acknowledgements

The authors are supported by National Institute on Alcohol Abuse and Alcoholism grant U01AA021912 and National Cancer Institute grants R01CA200597 and R01CA190844 (all to R.F.S.).

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Correspondence to Robert F. Schwabe.

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Yu, LX., Schwabe, R. The gut microbiome and liver cancer: mechanisms and clinical translation. Nat Rev Gastroenterol Hepatol 14, 527–539 (2017). https://doi.org/10.1038/nrgastro.2017.72

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