Colibactin-Producing E. Coli Associated With Increased Colorectal Cancer Risk in FAP Patients

A study from Kyoto Prefectural University of Medicine and collaborating Japanese institutions has found that patients with familial adenomatous polyposis (FAP) who carry colibactin-producing Escherichia coli (pks⁺ E. coli) in their colon polyps are over three times more likely to have a history of colorectal cancer than those who do not. The research was published in eGastroenterology.

The study highlights a potential connection between the gut microbiome and cancer risk in people with a strong genetic predisposition to colorectal cancer. Colibactin is a genotoxin produced by certain strains of E. coli that can damage DNA.

Preserved gut microbiota linked to presence of bacterium

The research team studied 75 FAP patients between 2018 and 2019, all of whom had not undergone colorectal surgery at the time of sample collection. These individuals retained their natural gut microbiota, allowing for analysis of microbial colonization. Samples from colon polyps and adjacent mucosal tissue were taken during endoscopy and examined for the presence of pks⁺ E. coli.

The study found that:

• The bacterium was commonly found in FAP patients, with higher prevalence among those who smoked.
• Patients who had undergone prior colorectal surgery showed no signs of pks⁺ E. coli, suggesting the importance of an intact microbiota for bacterial colonization.
• Among patients who had not received surgery, those with a history of colorectal cancer were 3.25 times more likely to carry the bacterium.
• Polyps colonized by pks⁺ E. coli displayed more DNA damage and higher levels of interleukin-6 (IL-6), a pro-inflammatory signaling molecule.

Bacterial toxin may contribute to cancer development

The authors propose that colibactin may contribute to colorectal cancer in FAP patients by inducing DNA damage and inflammatory responses in already at-risk tissue. The elevated presence of IL-6 suggests a possible role for chronic inflammation in this process.

While previous research has examined the role of colibactin in colorectal cancer, this is one of the first studies to focus specifically on FAP patients who had not undergone surgery, providing insight into the natural microbial environment in this high-risk group.

Future directions call for larger studies

The findings are based on a relatively small cohort and the authors emphasize that more extensive, multicenter studies are needed to validate the results. If confirmed, this line of research may inform early risk detection and new prevention strategies for patients with hereditary cancer syndromes.

Potential directions include:

• Preventive approaches targeting gut microbiota (such as probiotics or bacteriophage therapy)
• Screening for microbial biomarkers in stool or mucosal samples
• Development of therapies that limit colibactin-induced inflammation and genomic instability

Reference: Ishikawa H, Aoki R, Mutoh M, et al. Contribution of colibactin-producing Escherichia coli to colonic carcinogenesis. eGastroenterol. 2025. doi:10.1136/egastro-2024-1001770.1136/egastro-2024-100177

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