Gut microbiota dysbiosis intensified from healthy controls to non-metastatic CRC to colorectal liver metastasis (CRLM), with stage-specific functional reprogramming and a random forest model of nine taxa plus one virulence factor reaching 97.5% accuracy in separating CRLM from non-metastatic CRC, though prospective multicenter validation is required.
Key Findings
Results
Gut microbiota dysbiosis intensified as colorectal cancer progressed toward colorectal liver metastasis.
Fecal metagenomic sequencing was performed in 60 participants: healthy controls, non-metastatic CRC, and synchronous CRLM (n = 20 per group).
Dysbiosis was characterized by depletion of commensal flora and enrichment of specific genera.
Results
Specific genera, including Eikenella and Porphyromonas, were significantly enriched in CRLM.
The abstract reports 'significant enrichment of specific genera, such as Eikenella and Porphyromonas' alongside depletion of commensal flora.
Analysis was based on fecal metagenomic sequencing.
Results
The gut microbiome showed stage-specific functional remodeling between CRC and CRLM.
In non-metastatic CRC, functions were weighted toward infection- and virulence-related pathways.
In CRLM, functions shifted toward microbial secondary metabolism and stress adaptation.
Results
Network analysis showed a sparser and more compartmentalized microbial ecological structure in CRLM.
SPIEC-EASI-based co-occurrence network analysis was used.
[Clostridium] symbiosum, Campylobacter concisus, and Coprococcus eutactus emerged as module hubs in CRLM.
Results
A random forest model using nine core taxa and one virulence factor (VF0160 FeoAB) discriminated CRLM from non-metastatic CRC with 97.5% overall accuracy.
The model integrated nine core taxa and the virulence factor VF0160 FeoAB.
Accuracy was 97.5% in discriminating CRLM from non-metastatic CRC.
The authors state this indicates potential for fecal metagenomic biomarkers for risk stratification, but the cohort was small (20 per group) and prospective validation in larger multicenter cohorts is needed.
Conclusions
The authors propose that dysbiosis and functional reprogramming are strongly associated with CRLM progression, potentially via remodeling of the hepatic pre-metastatic niche through the gut-liver axis.
This is presented as a suggested mechanism, not directly demonstrated by the study's observational design.
Clinical translation requires prospective validation in larger multicenter cohorts.
What This Means
This study looked at the gut bacteria of 60 people: 20 healthy individuals, 20 with colorectal cancer that had not spread, and 20 with colorectal cancer that had already spread to the liver. Stool samples were sequenced to identify which microbes were present and what they were capable of doing. The researchers found that the gut microbial community became progressively more disrupted from healthy to non-metastatic cancer to liver metastasis, with fewer beneficial bacteria and more of certain bacteria such as Eikenella and Porphyromonas.
The functions of the microbes also differed by stage. In cancer without spread, bacterial functions tied to infection and virulence stood out, whereas in liver metastasis, functions related to secondary metabolism and stress adaptation were more prominent. The microbial communities in liver metastasis were also less interconnected and more divided into separate modules, with a few species acting as key hubs. A computer model using nine bacterial taxa and one virulence factor separated liver-metastasis patients from non-metastatic cancer patients with 97.5% accuracy.
This research suggests stool-based microbiome tests might one day help identify people at risk of liver metastasis. However, the study was small and observational, so it cannot show that the microbes cause metastasis, and such a high accuracy in a small group may not hold elsewhere. The authors emphasize that larger, prospective, multicenter studies are needed before any clinical use.
Sheng Y, Dai X, Lu J, Zhang H, Cai P. (2026). The Potential Role of Gut Microbiome Dysbiosis and Functional Reprogramming in Colorectal Liver Metastasis via the Gut-Liver Axis.. Cancer reports (Hoboken, N.J.). https://doi.org/10.1002/cnr2.70738