Hepatocellular Cancer and Gut Microbiome: Time to Untie Gordian's Knot

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death worldwide and the incidence is growing on a global scale. About 90% of cases develop on the cirrhotic liver and the etiology is multifactorial. Increasing number of studies suggest that gut microbiota influences the development and progression of liver diseases, including chronic hepatic inflammation, fibrosis, cirrhosis, and HCC. The key role of gut microbiota in carcinogenesis seems to be associated with genomic instability of host cells and immune dysregulation. Recent clinical studies showed that a stable and healthy microbiota initially could have the ability to resist the emergence of chronic inflammation and, therefore, prevent the induction of carcinogenic cells in various organs such as the esophagus, stomach, colon, and liver. The progression from inflammation to cancer is a stepwise process occurring by the concerted action of several factors such as dysbiosis, increased gut permeability, diet, metabolomic, genetic, and epigenetic changes. In this article, we aimed to review the possible role of gut microbiota in the development, progression, and treatment of HCC.