Colibactin 是最近鉴定的由 pks 大肠杆菌产生的致癌基因毒素。我们假设囊性纤维化 (CF) 相关的功能失调的粘液结构增加了宿主粘膜对大肠杆菌素诱导的 DNA 损伤的脆弱性。在这项初步研究中，我们测试了在成人 CF 和非 CF 患者的筛查和监测结肠镜检查过程中获得的看似健康的粘膜活检样本是否存在 pks 大肠杆菌，并研究了检测新型大肠杆菌素特异性 DNA 加合物的可能性这尚未在人类身上得到证实。虽然 CF 患者的 pks 大肠杆菌携带发生率较低（~8% vs 29%，p = 0.0015），但检测到大肠杆菌素诱导的 DNA 加合物形成，但仅在 CF 患者中且仅在未服用 CFTR 调节剂的患者中检测到药物。此外，在本研究中发现的唯一一位患有结肠癌的患者患有 CF，携带 pks 大肠杆菌，并且粘膜样本中存在大肠杆菌素诱导的 DNA 加合物。应进行更大规模的纵向随访研究，以扩展这些初步结果，并进一步支持大肠杆菌素衍生的 DNA 加合物的开发，以对患者及其风险进行分层。

Colibactin is a recently characterized pro-carcinogenic genotoxin produced by pks+ Escherichia coli. We hypothesized that cystic fibrosis (CF)-associated dysfunctional mucus structure increases the vulnerability of host mucosa to colibactin-induced DNA damage. In this pilot study, we tested healthy-appearing mucosal biopsy samples obtained during screening and surveillance colonoscopies of adult CF and non-CF patients for the presence of pks+ E. coli, and we investigated the possibility of detecting a novel colibactin-specific DNA adduct that has not been yet been demonstrated in humans. While CF patients had a lower incidence of pks+ E. coli carriage (~8% vs 29%, p = 0.0015), colibactin-induced DNA adduct formation was detected, but only in CF patients and only in those who were not taking CFTR modulator medications. Moreover, the only patient found to have colon cancer during this study had CF, harbored pks+ E. coli, and had colibactin-induced DNA adducts in the mucosal samples. Larger studies with longitudinal follow-up should be done to extend these initial results and further support the development of colibactin-derived DNA adducts to stratify patients and their risk.