AB094. SOH26AB_0466. The impact of Escherichia coli genotoxic metabolite colibactin on colorectal cancer risk and progression from dysplasia to carcinoma: a systematic review and meta-analysis

Background: Understanding of the role of the gut microbiome in colorectal cancer (CRC) development and progression is evolving. Colibactin is a genotoxin produced by strains of Escherichia coli (E. coli). Colibactin induces carcinogenic mutations, and mutational signatures associated with colibactin have been confirmed in CRC genomes. This review aimed to synthesize the impact of colibactin on CRC risk and on the transformation from normal tissue to dysplasia to cancer.

Methods: This systematic review and meta-analysis was prospectively registered on PROSPERO (ID: CRD420251163810). A systematic review of published literature was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. MEDLINE (PubMed), Embase (OvidSP), and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched using the terms “colorectal cancer”, “colibactin”, “genotoxic E. coli”, and “incidence”. Studies reporting on clinical data were included. Exclusively in vitro and pre-clinical studies were excluded. Data were meta-analysed using Review Manager 5.4.

Results: Nine studies were included. The presence of colibactin was associated with an increased risk of CRC in all included studies. The presence of Colibactin was significantly associated with an increased risk of developing CRC [odds ratio (OR) =2.77; 95% confidence interval (CI): 1.88–4.08; P<0.00001]. The presence of colibactin was also associated with an increased risk of progression from colorectal dysplasia to carcinoma (OR =2.04; 95% CI: 1.35–3.10; P=0.0008).

Conclusions: This meta-analysis demonstrates a significantly increased risk of CRC development and progression from dysplasia to carcinoma with the presence of colibactin-producing E. coli. Elements of the gut microbiome offer potentially actionable therapeutic targets to reduce CRC risk and development.