Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, University of Minnesota, Minneapolis, MN, USA.
Department of Environmental Health Sciences, School of Public Health, University of Minnesota, Minneapolis, MN, USA.
Gut Microbes. 2024 Jan-Dec;16(1):2387877. doi: 10.1080/19490976.2024.2387877. Epub 2024 Aug 12.
Colibactin is a recently characterized pro-carcinogenic genotoxin produced by . 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 , 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 carriage (~8% vs 29%, = 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 , 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.
大肠杆菌素是一种最近被描述的促癌遗传毒素，由 产生。我们假设囊性纤维化（CF）相关的功能失调的黏液结构增加了宿主黏膜对大肠杆菌素诱导的 DNA 损伤的易感性。在这项初步研究中，我们检测了在 CF 和非 CF 患者的筛查和监测结肠镜检查期间获得的健康外观的黏膜活检样本中 是否存在 ，并研究了检测尚未在人类中证明存在的新型大肠杆菌素特异性 DNA 加合物的可能性。虽然 CF 患者的 携带率较低（~8%比 29%，=0.0015），但检测到了大肠杆菌素诱导的 DNA 加合物形成，但仅在 CF 患者中，并且仅在未服用 CFTR 调节剂药物的患者中。此外，在这项研究中发现的唯一患有结肠癌的患者患有 CF，携带 ，并且在黏膜样本中存在大肠杆菌素诱导的 DNA 加合物。应该进行更大规模的具有纵向随访的研究，以扩展这些初步结果，并进一步支持开发基于大肠杆菌素衍生的 DNA 加合物来分层患者及其风险。
