Harnessing the Microbiome: Unveiling the Influence of the Gut Microbiota on Hepatobiliary Cancer Therapeutic Strategies

The gut microbiota significantly influences hepatobiliary cancer therapeutics. Growing evidence indicates that shifts in the gut microbial ecosystem are hallmarks of hepatocellular carcinoma and cholangiocarcinoma, strongly correlating with tumor development, therapeutic resistance, and patient survival. The composition of gut microbiota has emerged as a biomarker associated with treatment outcomes across various modalities, including chemotherapy, radiotherapy, targeted therapy, and immunotherapy. Beneficial bacterial communities enhance antitumor immunity, while pathogenic taxa are linked to reduced therapeutic efficacy. Multi-omics analyses have identified microbial metabolite signatures, such as short-chain fatty acids and bile acids, as potential targets for boosting antitumor responses. This review highlights the transformative potential of leveraging the gut microbiota to enhance precision oncology in hepatobiliary cancer. Future directions should prioritize personalized microbiota modulation approaches, combinatorial therapies targeting gut-liver axis crosstalk, and large-scale validation of microbial biomarkers across diverse populations.