Exploratory analysis of genotoxic Escherichia coli and Helicobacter pylori virulence in gastrointestinal carcinogenesis

Abstract

Gastrointestinal cancers remain among the leading causes of cancer-related mortality worldwide. Beyond environmental and hereditary determinants, increasing evidence suggests that the gut microbiota may contribute to carcinogenesis through persistent infection, expression of virulence factors, and production of genotoxic metabolites. In this context, Helicobacter pylori has been firmly implicated in gastric carcinogenesis, while colibactin-producing Escherichia coli has emerged as a potential contributor to colorectal cancer development. The aim of this study was to explore the presence of colibactin-associated E. coli and virulence factor-harboring H. pylori strains in gastrointestinal cancer patients from a Turkish cohort. Tumor samples were collected from 19 patients with colorectal cancer and 4 patients with gastric cancer. In colorectal cancer samples, the presence of colibactin was assessed by screening for key genes (clbA, clbB, clbN, and clbQ). In gastric cancer samples, major H. pylori virulence determinants, including ureA, cagA, and vacA, were evaluated. Colibactin-associated genes were detected in approximately 21% of colorectal cancer patients (4/19), whereas 75% of gastric cancer cases (3/4) were positive for H. pylori virulence factors. Whole-genome sequencing (WGS) of two colibactin-positive isolates identified them as Escherichia coli Nissle and Citrobacter braakii. Given the limited sample size and exploratory design, these results are descriptive and intended to provide preliminary insight rather than establish causality. In conclusion, this study provides early evidence supporting the potential presence of genotoxin-associated bacteria and virulent H. pylori strains in gastrointestinal cancer patients in T & uuml;rkiye. These findings underscore the need for larger, well-powered, and multi-omics-integrated studies to further elucidate the role of host-microbe interactions in gastrointestinal carcinogenesis.