The Gut Microbiome as a Biomarker and Therapeutic Target in Hepatocellular Carcinoma

SIMPLE SUMMARY: Hepatocellular carcinoma (HCC) is the most common type of liver cancer, accounting for approximately 85–90% of all cases of liver cancer worldwide. The gut microbiome can serve as a potential non-invasive biomarker for early HCC detection and may also impact the effectiveness of immunotherapy in cancer treatment. This review examines the gut microbiome’s role as a predictive and diagnostic marker for HCC and explores its potential as a novel therapeutic approach, particularly in the context of immunotherapy. ABSTRACT: The microbiome is pivotal in maintaining health and influencing disease by modulating essential inflammatory and immune responses. Hepatocellular carcinoma (HCC), ranking as the third most common cause of cancer-related fatalities globally, is influenced by the gut microbiome through bidirectional interactions between the gut and liver, as evidenced in both mouse models and human studies. Consequently, biomarkers based on gut microbiota represent promising non-invasive tools for the early detection of HCC. There is a growing body of evidence suggesting that the composition of the gut microbiota may play a role in the efficacy of immunotherapy in different types of cancer; thus, it could be used as a predictive biomarker. In this review, we will dissect the gut microbiome’s role as a potential predictive and diagnostic marker in HCC and evaluate the latest progress in leveraging the gut microbiome as a novel therapeutic avenue for HCC patients, with a special emphasis on immunotherapy.