The Potential Role of Gut Microbiome Dysbiosis and Functional Reprogramming in Colorectal Liver Metastasis via the Gut–Liver Axis
4 affiliations
- 1Health Science Center, Ningbo University Ningbo Zhejiang China
- 2Xiangshan Hospital of TCM Medical and Health Group Ningbo Zhejiang China
- 3Ningbo No.2 Hospital Ningbo Zhejiang China
- 4School of Marine Sciences, Ningbo University Ningbo Zhejiang China
Abstract
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.
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BibTeX
@article{sheng2026potential,
title = {{The Potential Role of Gut Microbiome Dysbiosis and Functional Reprogramming in Colorectal Liver Metastasis via the Gut–Liver Axis}},
author = {Yuejin Sheng and Xiaoyu Dai and Jiaqi Lu and Hao Zhang and Ping Cai},
journal = {Cancer Reports},
year = {2026},
month = nov,
doi = {10.1002/cnr2.70738},
url = {https://doi.org/10.1002/cnr2.70738},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - The Potential Role of Gut Microbiome Dysbiosis and Functional Reprogramming in Colorectal Liver Metastasis via the Gut–Liver Axis
AU - Yuejin Sheng
AU - Xiaoyu Dai
AU - Jiaqi Lu
AU - Hao Zhang
AU - Ping Cai
PY - 2026
DA - 2026/11/04
JO - Cancer Reports
DO - 10.1002/cnr2.70738
UR - https://doi.org/10.1002/cnr2.70738
AB - 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.
SN - 2573-8348
ER -