Abstract Hepatocellular carcinoma (HCC) is a highly aggressive malignancy characterized by complex metabolic dysregulation and immune evasion mechanisms, leading to poor prognosis and limited treatment efficacy. Growing evidence underscores the critical involvement of gut microbiota dysbiosis in HCC pathogenesis, wherein microbial communities and their bioactive metabolites dynamically influence the hepatic immune microenvironment and drive tumorigenesis. Emerging evidence indicates that Traditional Chinese Medicine (TCM) exerts therapeutic effects against HCC by modulating the gut-liver axis through multiple mechanisms, including remodeling gut microbial composition, regulating microbiota-derived metabolites, and fine-tuning hepatic immune responses, thus establishing a novel effective paradigm for HCC therapy. This article comprehensively reviews the intricate interactions between TCM and the gut microbiota-metabolism-immunity axis, elucidating the pivotal roles of gut microbiota and their metabolites in HCC pathogenesis and progression. Furthermore, we systematically summarize recent advances in understanding how TCM exerts anti-HCC effects through microbiota-mediated immunomodulation, with a particular focus on regulatory mechanisms involving microbial metabolites and hepatic immune responses. These findings provide valuable insights and establish a conceptual framework for future research in this burgeoning field. Graphical Abstract
Zhang et al. (Tue,) studied this question.