Genotoxic pks + E. coli is strongly associated with ileocolonic neoplasia in adults with Cystic Fibrosis.

BACKGROUND

Polyketide synthase island-positive (pks+) Escherichia coli is a genotoxic gut bacterium linked to colorectal cancer (CRC) tumorigenesis via the genotoxin colibactin. In adults with Cystic Fibrosis (CF), there is an increased incidence and earlier development of CRC but the biological mechanisms underlying this increased risk remain incompletely understood. We aimed to determine the prevalence of pks+ E. coli in adults with CF.

METHODS

Stool samples and DNA were analyzed from the SCREENCF study cohort. Metagenomic libraries were sequenced on the NovaSeq X Plus platform, using Illumina protocols. Detection of the pks island was assessed with polymerase chain reaction (PCR) targeting the clbB gene.

RESULTS

Of the 49 CF participants; pks+ E. coli was detected in 1/35 (3%) of the no pathology (NORMAL) group, 5/12 (42%) in the adenomatous polyps (AP) group, and 2/2 (100%) in the ileocolonic cancer (ICC) group. Individuals with any ileocolonic neoplasia were 34 times more likely to harbor pks+ E. coli than those with NORMAL colonoscopy findings (OR = 34.0, 95% CI 5.00-691, p = 0.002). The presence of pks+ E. coli correlated with higher overall E. coli burden (p = 0.0009), but not with fecal inflammation, other genotoxic bacterial species or overall bacterial composition.

CONCLUSION

pks+ E. coli is infrequently detected among adults with CF, but its presence is associated with ileocolonic neoplasia, indicating a potential role in pathogenesis. If validated in larger cohorts, pks+ E. coli could provide a clinically meaningful biomarker for early detection, risk stratification and a potential target for precision intervention.