Microbiota and Liver Cancer

Hepatocellular carcinoma (HCC) is the most prevalent cancer and a leading cause of cancer-related deaths worldwide. Chronic hepatitis B, hepatitis C, alcoholism, and non-alcohol fatty liver disease are the most common etiologies of HCC. Most etiologies lead to the oncogenesis pathways via chronic inflammation, which has been shown to be closely related to dysbiosis, the unbalanced status of symbionts and pathobionts. Trillions of microbes live in the human gastrointestinal tract, renowned as the gut microbiome, and perform a variety of functions that support human physiology. As they become more understood, these gut symbiotic microorganisms also cause diseases when they go wrong, including cancer. Given the tremendous abundance and physical proximity to our digestive tract, the gut microbiome has been widely studied for its association, mechanism, and even causality to liver cancer. In principle, the gut microbiome not only alters in composition along with liver disease progression, but also demonstrates the critical role in carcinogenesis by disrupting host immune response, abolishing liver metabolism, and inducing chronic inflammation. This chapter is organized to first introduce the relationships between cancer and the gut microbiome, and then to review the studies (from association to mechanism) looking at microbial roles in the gut-liver axis, HCC-inducing liver diseases, and HCC. Finally, according to the recently prominent advances in cancer immunotherapy, the last section will discuss the role and application of gut microbes in cancer treatment and the progress achieved in HCC immunotherapy. This compilation aims to provide a comprehensive review and up-to-date understanding of the gut microbiome in HCC and hopefully to inspire new ideas translating these pieces of knowledge into therapeutic strategies for patients.