Article Impact Level: HIGH Data Quality: STRONG Summary of Nature Medicine. https://doi.org/10.1038/s41591-025-03693-9 Dr. Gianmarco Piccinno et al.
Points
- A large-scale metagenomic study of 2,116 participants identified 19 key microbial species, including Fusobacterium nucleatum, as distinct markers strongly associated with colorectal cancer presence and progression.
- The predictive model using gut microbiome data achieved 85% accuracy in identifying colorectal cancer, especially in tumor-adjacent tissues where cancer-linked microbes were significantly enriched.
- Specific microbial signatures correlated with tumor location and stage, with an AUC of 0.66 for distinguishing right- versus left-sided tumors and certain strains linked to advanced cancer stages.
- The findings suggest gut microbiome disruptions may influence colorectal cancer development and highlight its promise as a non-invasive diagnostic tool requiring further causal research.
- Researchers propose microbiome profiling could reduce reliance on invasive procedures and advocate for clinical trials to develop early screening methods and personalized CRC interventions.
Summary
This study, published in Nature Medicine, aimed to explore the gut microbiome’s role in colorectal cancer (CRC) through large-scale metagenomic analysis of 2,116 participants, including patients with CRC (n=930), adenomas (n=210), and healthy controls (n=976). The research identified a microbial signature consisting of 19 key species, with Fusobacterium nucleatum and other oral-typical bacteria such as Parvimonas micra and Gemella morbillorum showing distinct associations with CRC. The model, which achieved an average accuracy of 85% in predicting CRC based solely on gut metagenomics, demonstrated that these microbes were enriched in CRC patients, especially in tumor-adjacent gut tissues. Additionally, the study found that these microbial signatures correlate with tumor location and stage, revealing insights into the potential mechanisms behind CRC progression.
The research also examined specific gut species about tumor characteristics, such as left-sided versus right-sided CRC, achieving an area under the curve (AUC) of 0.66 for distinguishing tumor locations. Notably, strain-specific signatures were identified for the commensal Ruminococcus bicirculans and Faecalibacterium prausnitzii, with specific subclades linked to later-stage CRC. The findings underline the microbiome’s potential as a non-invasive tool for early CRC detection and its use in personalized diagnostic approaches. The study emphasized the role of microbial balance in CRC, indicating that disruptions in the gut microbiome may influence cancer development, though further research is needed to establish causal links.
Ultimately, this work highlights the utility of microbiome profiling in clinical settings, particularly for non-invasive CRC screening. The study offers a promising avenue for developing metagenomic-based screening tools, potentially reducing reliance on invasive procedures like colonoscopy. The researchers advocate for further clinical trials to validate these findings and refine screening protocols to improve early detection and prevent CRC progression through targeted microbiome-based interventions.
Link to the article: https://www.nature.com/articles/s41591-025-03693-9
References Piccinno, G., Thompson, K. N., Manghi, P., Ghazi, A. R., Thomas, A. M., Blanco-Míguez, A., Asnicar, F., Mladenovic, K., Pinto, F., Armanini, F., Punčochář, M., Piperni, E., Heidrich, V., Fackelmann, G., Ferrero, G., Tarallo, S., Nguyen, L. H., Yan, Y., Keles, N. A., … Segata, N. (2025). Pooled analysis of 3,741 stool metagenomes from 18 cohorts for cross-stage and strain-level reproducible microbial biomarkers of colorectal cancer. Nature Medicine. https://doi.org/10.1038/s41591-025-03693-9
