Topic: Microbiome–Liver Axis in Hepatocellular Carcinoma: Mechanisms and Therapeutic Insights

Despite major progress in the understanding and treatment of hepatocellular carcinoma (HCC), the complex interplay between the host microbiome and liver carcinogenesis remains a frontier with substantial clinical implications. Mounting evidence highlights the gut-liver axis and the broader microbiome as key regulators of HCC initiation, progression, and therapeutic response. Gut dysbiosis, microbial metabolites, and microbiome-driven modulation of hepatic immunity are increasingly recognized not only as contributors to chronic inflammation and fibrosis—core drivers of HCC—but also as direct influencers of tumor biology and patient outcomes. These intricate relationships position the microbiome as a pivotal factor in deciphering HCC heterogeneity and identifying novel therapeutic vulnerabilities.

Concurrently, breakthroughs in high-throughput sequencing, multi-omics integration, and functional genomics offer powerful tools to dissect microbial-host interactions. The convergence of mechanistic insights and technological innovation is paving the way for new diagnostic and therapeutic strategies targeting the microbiome-liver axis. This Special Issue aims to bridge fundamental discoveries with clinical translation, deepening our understanding of the molecular mechanisms linking the microbiome to HCC and exploring its potential as a source of biomarkers and therapeutic targets—including probiotics, prebiotics, fecal microbiota transplantation (FMT), and targeted microbial modulation. We welcome original research articles, reviews, mini-reviews, clinical trials, case reports, commentaries, methodological studies, and perspectives focused on, but not limited to, the following topics:

1. Differences of microbiome among HCC with various etiologies;
2. Alterations of microbiome during the development of HCC;
3. Impact of sex-related microbiome on susceptibility and progression in HCC;
4. Explorations of diet–microbiome interaction on HCC development;
5. Investigations of microbial characteristics at the strain level in HCC;
6. Advances in bioinformatics tools and their applications in microbiome research of HCC;
7. The molecular mechanism of microbial translocation to liver;
8. The role of microbial gut-liver axis in HCC development;
9. The microbiota-immune crosstalk in HCC progression;
10. The role of microbial metabolites in HCC progression;
11. The mechanism of pathogenic microbes on HCC development and their targeted interventional strategies;
12. Application of probiotics in HCC prevention;
13. Prediction of therapy response to HCC based on microbiome;
14. Clinical applications of fecal microbiota transplantation in HCC therapy;
15. Insights of bacteriophage therapy targeting pro-tumor microbes in HCC.

We cordially invite original research and review articles spanning basic, translational, and clinical studies on microbiome-related mechanisms, diagnostics, and therapies in HCC.

Gut–Liver axis; microbiome–host interactions; gut dysbiosis; microbial metabolites; hepatic immunity; multi-omics; microbiome-based therapeutics; probiotics; fecal microbiota transplantation (FMT)