Chan Christopher, Coffey Michael, Murphy Caitlin, McKay Isabelle, Abdu Jumaana, Paida Keerti, Tam Rachel Y, Wrigley-Carr Hannah, Prentice Bernadette, Owens Louisa, Belessis Yvonne, Chuang Sandra, Jaffe Adam, van Dorst Josie, Ooi Chee Y
School of Clinical Medicine, Discipline of Paediatrics & Child Health, UNSW Medicine & Health, University of New South Wales, Sydney, NSW 2031, Australia.
Department of Gastroenterology, Sydney Children's Hospital, Randwick, NSW 2031, Australia.
Microorganisms. 2025 Mar 18;13(3):681. doi: 10.3390/microorganisms13030681.
Cystic fibrosis (CF) patients experience higher risks of colorectal cancer but the pathogenesis is unclear. In the general population, polyketide synthase-positive (pks) is implicated in intestinal carcinogenesis via the production of colibactin; however, the relevance in CF is unknown. In this study, we investigate pks prevalence in CF and potential associations between pks, gastrointestinal inflammation, and microbiome dynamics with fecal calprotectin and 16SrRNA gene taxonomic data. Cross-sectional analysis demonstrated no difference in pks carriage between CF patients and healthy controls, 21/55 (38%) vs. 26/55 (47%), = 0.32. Pks was not associated with significant differences in mean (SD) calprotectin concentration (124 (154) vs. 158 (268) mg/kg; = 0.60), microbial richness (159 (76.5) vs. 147 (70.4); = 0.50) or Shannon diversity index (2.78 (0.77) vs. 2.65 (0.74); = 0.50) in CF. Additionally, there was no association with exocrine pancreatic status ( = 0.2) or overall antibiotic use ( = 0.6). Longitudinally, CF subjects demonstrated intra-individual variation in pks presence but no significant difference in overall prevalence. Future investigation into the effects of repeat exposure on risk profile and analysis of older CF cohorts is necessary to identify if associations with colorectal cancer exist.
囊性纤维化(CF)患者患结直肠癌的风险更高,但其发病机制尚不清楚。在普通人群中,聚酮合酶阳性(pks)通过产生大肠杆菌素参与肠道致癌过程;然而,其在CF中的相关性尚不清楚。在本研究中,我们调查了CF中pks的流行情况,以及pks、胃肠道炎症和微生物群动态与粪便钙卫蛋白和16SrRNA基因分类数据之间的潜在关联。横断面分析显示,CF患者和健康对照之间pks携带情况无差异,分别为21/55(38%)和26/55(47%),P = 0.32。在CF中,pks与平均(标准差)钙卫蛋白浓度(124(154)对158(268)mg/kg;P = 0.60)、微生物丰富度(159(76.5)对147(70.4);P = 0.50)或香农多样性指数(2.78(0.77)对2.65(0.74);P = 0.50)的显著差异无关。此外,与外分泌胰腺状态(P = 0.2)或总体抗生素使用情况(P = 0.6)也无关联。纵向来看,CF受试者的pks存在情况存在个体内差异,但总体患病率无显著差异。未来有必要对重复暴露对风险特征的影响进行调查,并对年龄较大的CF队列进行分析,以确定是否存在与结直肠癌的关联。