The Potential Role of Gut Microbiome Dysbiosis and Functional Reprogramming in Colorectal Liver Metastasis via the Gut–Liver Axis
Yuejin Sheng, Xiaoyu Dai, Jiaqi Lu, Hao Zhang, Ping CaiABSTRACT
Background
Colorectal liver metastasis (CRLM) is a leading cause of mortality in colorectal cancer (CRC), yet current surveillance often misses occult micrometastases, underscoring an urgent need for early non‐invasive biomarkers and mechanistic insights.
Aims
This study aimed to investigate gut microbiota dysbiosis and functional alterations associated with CRLM and explore potential non‐invasive biomarkers.
Methods and Results
Fecal metagenomic sequencing was performed in 60 participants, comprising healthy controls, patients with non‐metastatic CRC, and patients with synchronous CRLM ( n = 20 per group). Microbial composition, functional pathways, co‐occurrence networks, and clinical associations were systematically analyzed, and a random forest model was constructed to identify potential diagnostic biomarkers. Results showed that gut microbiota dysbiosis intensified as CRC progressed toward CRLM, characterized by the depletion of commensal flora and significant enrichment of specific genera, such as Eikenella and Porphyromonas . Functionally, the gut microbiome displayed stage‐specific remodeling, shifting from infection‐ and virulence‐related pathways in CRC to functions associated with microbial secondary metabolism and stress adaptation in CRLM. Furthermore, SPIEC‐EASI‐based network analysis revealed a sparser and more compartmentalized microbial ecological structure in CRLM, with [Clostridium] symbiosum , Campylobacter concisus , and Coprococcus eutactus emerging as module hubs. A random forest model integrating nine core taxa and one virulence factor (VF0160 FeoAB ) achieved an overall 97.5% classification accuracy in discriminating CRLM from non‐metastatic CRC, indicating the potential of fecal metagenomic biomarkers for future risk stratification. However, prospective validation in larger multicenter cohorts is required before clinical translational utility.
Conclusion
Collectively, our findings suggest that gut microbiota dysbiosis and functional reprogramming are strongly associated with CRLM progression, potentially through remodeling the hepatic pre‐metastatic niche via the gut‐liver axis.