News Report: Bacteriophage in Bacteroides Fragilis Associated with Colorectal Cancer

Investigators examined intraspecies genetic variation in the gut bacterium Bacteroides fragilis and found that isolates from patients with colorectal cancer (CRC) were more likely to be infected with specific Caudoviricetes prophages than isolates from individuals without cancer.

This finding is framed within broader efforts to understand why B. fragilis, a bacterium commonly present in healthy individuals, is also repeatedly implicated in CRC-associated dysbiosis. Rather than focusing solely on species-level abundance, the study analyzed bacterial genetic variation to determine whether particular intraspecies features—specifically prophage infections—were associated with CRC. The work tracks the signal from an initial isolate-based genomic analysis through validation in an independent metagenomic cohort to assess whether the association persists beyond the original collection.

The research began with a highly specific collection of B. fragilis isolates obtained from CRC patients and controls. Using a pangenome-wide association study, investigators identified intraspecies genetic variations linked to CRC status. These variations corresponded to infection with specific Caudoviricetes prophages. The findings from this isolate-based discovery phase informed targeted evaluation in a larger validation dataset.

Replication was then performed in a metagenome sequencing cohort of fecal samples from 877 individuals with and without colorectal cancer. In this independent dataset, CRC patients were approximately twice as likely as controls to have detectable levels of the identified prophage sequences (odds ratio 2.05; p = 2.522 × 10⁻⁷; SE = 0.139). These analyses used mixed-effects logistic regression with cohort included as a random effect. The validation results are described as supporting the initial association observed in the isolate collection.

Alongside these cross-cohort comparisons, the investigators characterize the findings as associative rather than causal. The study does not establish whether prophage infection contributes directly to colorectal carcinogenesis or instead reflects broader microbial ecosystem changes in CRC-associated dysbiosis. The authors note that the work highlights a potential link between one of the most implicated bacterial species in CRC and specific phages, suggesting a more complex role for bacteriophages in CRC-related microbial disruption.

The paper concludes by suggesting that, if confirmed in further studies, these prophages may have potential as biomarkers for colorectal cancer. However, the findings are presented as an early step in clarifying the relationship between bacterial intraspecies variation and CRC rather than as definitive evidence of causation.

Key Takeaways:

• A pangenome-wide association study identified specific Caudoviricetes prophages infecting Bacteroides fragilis isolates from colorectal cancer patients more frequently than controls.
• The association was validated in an independent metagenomic cohort of 877 individuals, with CRC patients approximately twice as likely to have detectable levels of the prophages.
• The findings are associative rather than causal and suggest that bacteriophages may contribute to CRC-related dysbiosis or serve as potential biomarkers pending further validation.