The intestinal microbiota and hepatocellular carcinoma

Abstract

The microbiota and its collective genomes, i.e., microbiome, have recently attracted major interest in the scientific community. Especially the largest microbial community of the human body, the intestinal microbiota, is assumed to play a crucial role in many gastrointestinal, pancreatic and liver disorders. Several preclinical and clinical investigations have shown that liver diseases at various stages exhibit substantial changes in their microbiome compared to healthy controls, also defined as dysbiosis. The most profound changes have been observed in the stage of liver cirrhosis, and importantly, it is clinically well established that interference with the intestinal microbiota, e.g., rifaximin improves complications of liver cirrhosis, such as hepatic encephalopathy. It is currently unclear which factors drive the evolution of hepatocellular carcinoma (HCC), which usually appears in a cirrhotic liver. Pro-inflammatory signals, bacteria, and related metabolites might be involved. Several studies have recently assessed the role of the intestinal microbiota in HCC. Here, various reports could demonstrate that especially the abundance of pro-inflammatory intestinal communities, such as Proteobacteria and Enterobacteriaceae are increased. Furthermore, some studies in HCC have shown, that microbiome alterations are associated with decreased levels of butyrate-producing Clostridiales and species, known for their anti-inflammatory potential, like Akkermansia muciniphila. These strains could contribute to the overall pro-inflammatory phenotype of this malignancy. Furthermore, several preclinical studies could convincingly show that intestinal bacteria are involved in liver carcinogenesis. Overall, it can be concluded that the intestinal microbiota might play a crucial role in the pathophysiology of hepatic carcinogenesis.

Keywords

• inflammation
• liver cancer
• metagenomics
• metabolites
• microbiome.