August's Paper of the Month study adds to the data looking at associations between the gut microbiome and colorectal cancer (CRC).
Pooled analysis of 3,741 stool metagenomes from 18 cohorts for cross-stage and strain-level reproducible microbial biomarkers of colorectal cancer - Ren B, Li J, Gevers D, et al. Journal: Nature Medicine, June 2025.
What is known about the subject
- Colorectal cancer (CRC) remains one of the leading causes of cancer-related deaths worldwide.
- Early detection is crucial, yet current screening methods (e.g. colonoscopy, FIT tests) have limitations in terms of sensitivity, specificity, or patient adherence.
- Previous studies have suggested that the gut microbiome harbors microbial signatures associated with CRC development; however, most cohorts were small and lacked reproducibility across populations.
What the study adds
- This study pooled 3,741 stool metagenomes from 18 international cohorts, including patients with CRC, adenomas, and healthy controls.
- Using standardised metagenomic pipelines and machine learning, the authors identified a robust microbiome-based predictive model for CRC, achieving an AUC of 0.85 across validation sets.
- Novel microbial species (e.g. diverse Fusobacterium nucleatum clades, newly profiled Ruminococcus and Faecalibacterium subclades) were consistently associated with CRC and its progression.
- The microbiome could differentiate between left-sided and right-sided CRC (AUC = 0.66), with taxa associated with the oral cavity enriched in right-sided disease.
- Importantly, strain-level resolution revealed dynamic microbial shifts, with some subclades of Ruminococcus bicirculans and Faecalibacterium prausnitzii being linked to advanced-stage CRC.
Implications for colorectal practice
- The study underscores the importance of reliably identifying microbiome biomarkers that can be used in stool-based screening strategies
- The study identifies the compositional and structural features of the microbiome that might be associated with disease progression
- Stool metagenomic testing could become a noninvasive adjunct or alternative to current CRC screening strategies.The ability to identify tumour stage and location via microbial profiles could support risk stratification