A Meta-Analysis on the Association of Colibactin-Producing pks+ Escherichia coli with the Development of Colorectal Cancer Original paper

What was studied?

This study performed a meta-analysis to clarify whether carrying colibactin-producing pks+ Escherichia coli associates with a higher risk of colorectal cancer (CRC), because prior individual studies reported conflicting results. The authors systematically searched major databases up to October 18, 2021, extracted case–control and cohort data where CRC status was confirmed and pks genes were detected in human samples, assessed study quality with the Newcastle–Ottawa Scale, and pooled odds ratios using fixed- or random-effects models based on heterogeneity.

Who was studied?

The analysis combined human participants from 12 eligible studies published between 2013 and 2021, most of which used case–control designs. Across studies, “cases” were patients with confirmed CRC and “controls” were cancer-free individuals selected using each study’s criteria. Investigators detected pks+ E. coli (or colibactin genes) primarily in tissue or stool samples, and studies came from multiple countries spanning Western and non-Western regions, enabling subgroup comparisons by geography and sample type.

What were the most important findings?

This meta-analysis found a consistent association between carriage of pks-positive Escherichia coli and colorectal cancer, meaning people with colorectal cancer more often carried colibactin-capable E. coli than controls across the included studies. When the authors accounted for between-study differences by removing studies that disproportionately drove heterogeneity, the association persisted and became more internally consistent, supporting pks positivity as a stable functional signal rather than a chance finding. Subgroup analyses strengthened the microbiome-signature interpretation by showing the relationship was clearer in studies from Western settings and when investigators detected pks-positive bacteria directly from colonic tissue, which fits a mechanism that depends on close mucosal proximity for colibactin activity. Overall, the findings support an “MMA” framed as mucosa-associated pks-positive E. coli as a colorectal cancer–linked microbial feature, consistent with colibactin’s established ability to cause DNA damage and promote mutational injury that can contribute to tumorigenesis.

What are the greatest implications of this study?

Clinically, this meta-analysis supports treating pks+ E. coli carriage as a meaningful functional microbiome risk feature for CRC, especially when detected in tissue and in settings reflecting Western exposure patterns. It also suggests practical translational directions: pks+ E. coli could help distinguish higher-risk individuals and may contribute to early detection strategies in high-risk patients, while reinforcing the rationale for interventions that reduce mucosa-associated colonization or suppress colibactin’s downstream genotoxic effects. At the same time, the authors emphasize that limitations—variable sample sizes, inconsistent specimen handling across studies, and uneven geographic representation—justify cautious interpretation and motivate broader, standardized studies before routine clinical adoption.