From Gut Microbiota to Hepatic Pre-Metastatic Niches: Mechanism and Translational Prospects of the Gut-Liver Axis in Regulating Colorectal Cancer Liver Metastasis.

Colorectal cancer (CRC) is one of the most common malignancies worldwide, and liver metastasis remains a major contributor to poor prognosis and treatment failure. Increasing evidence indicates that the gut-liver axis plays a critical role in colorectal cancer liver metastasis (CRLM) by linking intestinal microbial alterations with hepatic microenvironmental remodeling. Gut dysbiosis and intestinal barrier disruption facilitate the translocation of microbial components and metabolites through the portal circulation, contributing to hepatic immune remodeling, extracellular matrix alteration, and the establishment of a pre-metastatic niche favorable for tumor colonization. During metastatic progression, specific tumor-associated microorganisms may further promote circulating tumor cell (CTC) survival, immune evasion, and metastatic adaptation, while intratumoral microbiome alterations and metabolic reprogramming may influence tumor growth and therapeutic responses. This review summarizes the current understanding of gut-liver axis-mediated regulation of CRLM, focusing on intestinal barrier dysfunction, microbial translocation, hepatic pre-metastatic niche formation, tumor cell-microbiota interactions, and emerging clinical applications. Unlike previous reviews that have primarily focused on gut microbiota alterations in colorectal carcinogenesis, this review emphasizes the contribution of gut-derived microbial signals to liver-specific metastatic evolution. In addition, we discuss current challenges, including limited human causal evidence, technical issues in low-biomass microbiome analysis, and the need for longitudinal clinical validation. Future integration of spatial multiomics, prospective cohorts, and personalized microbiome-based interventions may provide new opportunities for early risk prediction and precision management of CRLM.