Host–Microbiota Interactions in Liver Inflammation and Cancer
1
ImmunoConcEpT, CNRS, UMR 5164, University of Bordeaux, F-33000 Bordeaux, France
2
Department of Medicine, McGill University, Montreal, QC H3G 0B1, Canada
*
Author to whom correspondence should be addressed.
Cancers 2021, 13(17), 4342; https://doi.org/10.3390/cancers13174342
Submission received: 1 August 2021
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Revised: 20 August 2021
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Accepted: 24 August 2021
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Published: 27 August 2021
(This article belongs to the Special Issue Inflammation and Tumor)
Simple Summary
Hepatocellular carcinoma (HCC) is a difficult to treat liver cancer that generally arises in individuals suffering from alcoholic or non-alcoholic fatty liver diseases. Inflammation, tissue injury and fibrosis are important precursors of HCC. In this review, we explore the links between the microbiota, inflammation and carcinogenesis in the context of HCC. We discuss how the gut and liver communicate and how microbial molecules, including structural components and metabolites, elicit inflammation and tumorigenesis in the liver. A better understanding of microbiota-dependent mechanisms of liver cancer development might lead to novel microbial-based therapeutic approaches.
Abstract
Hepatocellular carcinoma (HCC) is a classical inflammation-promoted cancer that occurs in a setting of liver diseases, including nonalcoholic fatty liver disease (NAFLD) or alcoholic liver disease (ALD). These pathologies share key characteristics, notably intestinal dysbiosis, increased intestinal permeability and an imbalance in bile acids, choline, fatty acids and ethanol metabolites. Translocation of microbial- and danger-associated molecular patterns (MAMPs and DAMPs) from the gut to the liver elicits profound chronic inflammation, leading to severe hepatic injury and eventually HCC progression. In this review, we first describe how the gut and the liver communicate and discuss mechanisms by which the intestinal microbiota elicit hepatic inflammation and HCC. We focus on the role of microbial products, e.g., MAMPs, host inflammatory effectors and host–microbiome-derived metabolites in tumor-promoting mechanisms, including cell death and senescence. Last, we explore the potential of harnessing the microbiota to treat liver diseases and HCC.
