Inverse Correlation between pks-Carrying Escherichia coli Abundance in Colorectal Cancer Liver Metastases and the Number of Organs Involved in Recurrence

Colibactin, a genotoxin produced by <i>Escherichia coli</i> strains harboring the polyketide synthetase (<i>pks</i>) gene cluster, causes DNA damage and somatic mutations. <i>pks</i>⁺<i>E. coli</i> is enriched in primary colorectal cancer (CRC) and is associated with clonal driver mutations, but its role in CRC liver metastasis is unclear. We assessed the association of <i>pks⁺ E. coli</i> in CRC liver metastasis tissues with systemic and local immune responses and the number of organs involved in recurrence using specimens and clinicopathological data from 239 patients with CRC liver metastasis who underwent metastasectomy. The levels of <i>pks</i>⁺<i>E. coli</i> in fresh-frozen specimens were quantified as "very low" (<50th percentile), "low" (50th to 75th percentiles), and "high" (>75th percentile) using a digital PCR. Immunohistochemical analysis of tumor-infiltrating immune cells was performed using tissue microarrays. Systemic inflammation was evaluated using serum C-reactive protein (CRP) levels. <i>pks</i>⁺<i>E. coli</i> was detected in 66.7% (157 of 239) liver metastasis tissues. Higher levels of <i>pks</i>⁺<i>E. coli</i> were associated with decreased serum CRP levels and reduced densities of CD4⁺ cells and CD163⁺ cells in the tumor-immune microenvironment. The "high" <i>pks⁺ E. coli</i> group had fewer metastatic organs involved than the "very low" <i>pks⁺ E. coli</i> group (mean number of organs: 1.00 vs. 1.23). These findings suggest that <i>pks</i>⁺<i>E. coli</i> play a modulating role in CRC metastasis.