Metatranscriptomic analysis of tumor and control colon tissue revealed that Fusobacterium nucleatum and co-active oral bacteria show increased virulence factor expression in tumors, form a microbial consortium correlated with host inflammation and metastasis genes, and share gene expression profiles partially overlapping with the oral cavity, suggesting a stable oral-gut microbial interaction driving colorectal cancer tumorigenesis.
Fusobacterium nucleatum was more transcriptionally active in tumor tissue than in control gut mucosa.
F. nucleatum activity in tumors was positively correlated with the activity of other oral bacteria and certain gut bacteria.
Bacterial functional gene expression profiles differed between tumor and control tissue, with distinct metabolic signatures in each.
Potential virulence factors from F. nucleatum were significantly more highly expressed in tumor tissue than in control tissue.
The Fusobacterium-Peptostreptococcus-Hungatella microbial cluster showed significant correlations with human host genes involved in inflammation and metastasis.
For the first time, gene expression profiles of oral bacteria in the gut tumor tissue were compared to their expression in the oral cavity (subgingival sulcus).
The study design used metatranscriptomics (RNA-based analysis) to assess microbial activity rather than community composition alone.
This research suggests that in colorectal cancer, certain bacteria — particularly Fusobacterium nucleatum and several other bacteria normally found in the mouth — are not just present in tumor tissue but are actively expressing genes, including genes that help them colonize and potentially drive tumor growth. By analyzing RNA (which reflects what genes are actively being used) rather than DNA (which only shows what is present), the researchers found that this group of bacteria forms a coordinated cluster in colon tumors and that their activity correlates with human genes involved in inflammation and cancer spread. This is important because it moves beyond simply cataloguing which bacteria are found in tumors and instead shows what those bacteria are actually doing. The study also found that bacterial gene activity in tumors shifts toward amino acid metabolism and production of lipopolysaccharide — a molecule from bacterial cell walls known to trigger immune responses — compared to normal colon tissue, where carbon metabolism genes dominate. This suggests that the tumor environment may be reshaping how bacteria function, or that bacteria with these metabolic activities may thrive specifically in tumors. The elevated lipopolysaccharide-related gene expression is particularly notable given the known role of this molecule in chronic inflammation, which can promote cancer progression. Perhaps most strikingly, this research suggests a link between the oral microbiome and colon tumors: the same cluster of bacteria found actively co-operating in tumors was also partially present and active in the patients' gum pockets (subgingival sulcus). While thousands of bacterial genes were expressed differently between the mouth and the tumor, critical virulence factor genes showed similar expression levels in both locations. This supports the idea that oral bacteria may travel from the mouth to the colon, maintain their disease-promoting capabilities, and work together as a consortium to contribute to colorectal cancer development.
Buetas E, Conde-Pérez K, Concha &, Celeiro C, Noguera J, Bou G, et al.. (2026). Metatranscriptomic analysis of the microbiota of tumor tissue in colon cancer.. Microbiome. https://doi.org/10.1186/s40168-026-02372-2