Intestinal-hepatic axis-mediated hepatocarcinogenesis and traditional Chinese medicine intervention strategies

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide. Growing evidence indicates that the gut–liver axis plays a critical role in HCC pathogenesis through interactions between gut microbiota and liver physiology, involving microbial translocation, metabolite signaling, and immune and metabolic reprogramming within the hepatic microenvironment. Owing to its multi-component and multi-target properties, Traditional Chinese Medicine (TCM) represents a promising strategy for modulating this axis. This review summarizes current evidence on gut microbial communities, key metabolites, and the microbiota-modulating potential of TCM in HCC progression. This review examines current evidence on gut microbiota–mediated mechanisms in HCC and the modulatory effects of TCM via the gut–liver axis. Literature was retrieved from PubMed, Web of Science, Embase, CNKI up to December 2025. Eligible studies included experimental, animal, and clinical investigations addressing gut microbiota dysbiosis, microbial metabolites, intestinal barrier dysfunction, intratumoral microbiota, and TCM interventions in HCC or related chronic liver diseases. Gut microbiota dysbiosis is a key driver of HCC through disruption of the gut–liver axis, characterized by reduced microbial diversity, intestinal barrier impairment, and microbial translocation–induced inflammation. Microbiota-derived metabolites, including lipopolysaccharides, secondary bile acids, short-chain fatty acids, ethanol metabolites, amino acid derivatives and lipid metabolites play central roles in regulating inflammatory signaling, immune responses, and tumor metabolism. TCM formulas and active compounds can restore gut microbial balance, strengthen intestinal barrier function, regulate microbial metabolites, and suppress pro-inflammatory and pro-tumorigenic signaling pathways, thereby attenuating hepatic inflammation and inhibiting HCC progression. Gut microbiota dysbiosis along the gut–liver axis plays a central role in HCC representing a promising therapeutic target. TCM may modulate this axis through multi-component, multi-target mechanisms, but further clinical and multi-omics studies are required to establish causal links and enable precision therapy.