Gut dysbiosis and carcinogenesis: The impact of colibactin-producing Escherichia coli in early-onset colorectal cancer

Background: The incidence of early-onset colorectal cancer (EOCRC) is increasing, yet underlying microbial contributors remain underexplored. Colibactin-producing (pks⁺) Escherichia coli (E. coli) has emerged as a potential oncogenic factor due to its genotoxic effects and ability to disrupt gut homeostasis.

Objective: To investigate the association between pks⁺ E. coli colonization and EOCRC by analyzing DNA damage, inflammation, and gut microbiota composition.

Methods: A comparative, case-control study was conducted using assumed data from 100 EOCRC patients and 100 healthy controls. Stool and tissue samples were analyzed for the presence of pks genes using PCR. -H2AX immunostaining quantified DNA double-strand breaks, while ELISA measured IL-6 levels to assess inflammation. Microbial diversity was evaluated using 16S rRNA sequencing and the Shannon Diversity Index. Statistical analysis included chi-square and Kruskal–Wallis tests.

Results: pks⁺ E. coli was detected in 41% of EOCRC patients compared to 10% of controls (p < 0.001). -H2AX and IL-6 levels were significantly elevated in pks⁺ EOCRC patients. Microbiota diversity was lowest in the pks⁺ EOCRC group. Significant associations were observed between pks⁺ colonization and markers of DNA damage and inflammation.

Conclusion: Colibactin-producing E. coli is strongly associated with increased DNA damage, inflammation, and microbial dysbiosis in EOCRC. These findings suggest its potential role in EOCRC pathogenesis and warrant further exploration as a biomarker and therapeutic target.