Gut microbiota-driven pre-metastatic niche formation in colorectal cancer liver metastasis: mechanisms and translational significance

Liver metastasis of colorectal cancer (CRC) remains a major clinical challenge, closely linked to poor prognosis and limited therapeutic efficacy. Emerging evidence implicates the gut microbiota in orchestrating the formation and maturation of the hepatic pre-metastatic niche (PMN) through the gut–liver axis. Dysbiosis-induced disruption of intestinal barrier integrity facilitates microbial translocation, which triggers hepatic inflammation, immune suppression, metabolic reprogramming, and vascular remodelling, together creating a permissive soil for metastatic seeding. Among pathogenic taxa, Fusobacterium nucleatum has emerged as a key driver because it persistently colonises both primary tumours and hepatic metastases while modulating immunotolerance and chemoresistance. Therapeutically, narrow-spectrum antimicrobial approaches that target pro-metastatic taxa show promise for safely and selectively correcting microbiota-mediated PMN formation. In addition, faecal microbiota transplantation (FMT) combined with immune checkpoint inhibitors and anti-angiogenic therapy has yielded encouraging responses in refractory metastatic CRC by boosting anti-tumour immunity and restoring hepatic microvascular architecture. Future research should integrate multidimensional biomarker assessment with personalised, microbiota-based therapeutic frameworks to achieve effective and durable prevention of CRC liver metastasis.