The Gut Microbiome and Hepatocellular Carcinoma: Implications for Early Diagnostic Biomarkers and Novel Therapies

Hepatocellular carcinoma (HCC) ranks the third place among all causes inducing cancer-associated mortality, worldwide. HCC nearly exclusively occurs in cases suffering from chronic liver disease (CLD), which results from the vicious cycle of liver damage, inflammation, and regeneration possibly lasting for dozens of years. Recently, more and more investigation on microbiome-gut-liver axis enhances our understanding toward how gut microbiota promotes liver disease and even HCC development. In this review, we summarize the mechanisms underlying the effect of gut microbiota on promoting HCC occurrence, with the focus on key pathways such as bacterial dysbiosis, leaky gut, bacterial metabolites, and microorganism-related molecular patterns, which promote liver inflammation, genotoxicity, and fibrosis that finally lead to cancer occurrence. Furthermore, we discuss gut microbiota's important potential to be the early diagnostic biomarker for HCC. Gut microbiota may be the candidate targets to simultaneously prevent CLD and HCC occurrence among advanced liver disease cases. We outlook the gut microbiota-targeting treatments in detail to prevent CLD and HCC progression.