Mignozzi Silvia, De Pinto Giuseppe, Guglielmetti Simone, Riso Patrizia, Cintolo Marcello, Penagini Roberto, Gargari Giorgio, Marino Mirko, Ciafardini Clorinda, Ferraroni Monica, Bonzi Rossella, Mutignani Massimiliano, La Vecchia Carlo, Rossi Marta
Department of Clinical Science and Community Health, Dipartimento di Eccellenza 2023-2027, University of Milan, Milan, Italy.
Department of Biotechnology and Biosciences, University of Milan Bicocca, Milan, Italy.
PLoS One. 2025 Mar 28;20(3):e0319750. doi: 10.1371/journal.pone.0319750. eCollection 2025.
An involvement of gut microbiota on the possible role of aspirin against intestinal adenoma (IA) and colorectal cancer (CRC) has been suggested. To further investigate this issue, we analyzed data from an Italian case-control study including 100 incident histologically confirmed CRC cases, as well as 100 IA and 100 controls without lesions from colonoscopy, matched to cases by center, sex and age. Serum zonulin was assessed by ELISA kit and blood bacterial DNA by qPCR and 16S rRNA gene profiling. Fifty-eight subjects (19.3%) reported aspirin use of ≥ 100 mg/day for cardiovascular prevention for at least six months. To evaluate the relationship between aspirin and IA and CRC risks, the odds ratios (OR) of IA and CRC and the corresponding 95% confidence intervals (CI) for aspirin use were estimated using a logistic regression model conditioned on the matching variable and adjusted for education and a model adjusted for several potential confounders including BMI and cardiovascular diseases. We evaluated whether the levels of zonulin and bacterial DNA data were different in aspirin users vs non-users through the rank sum and chi-square tests. Aspirin use was associated with a reduced risk of IA (OR = 0.45, 95% CI = 0.21-0.94) and CRC (OR = 0.43, 95% CI = 0.19-0.96). Similar results were obtained using the fully adjusted model. We found lower genera and operational taxonomic units (OTUs) richness of blood bacterial community in aspirin users vs non-users overall and in cases and controls. The genera Cutibacterium, Sphingomonas, Gaiella, Delftia and Romboutsia, order Microtrichales and class Deltaproteobacteria were different according to aspirin use. This study provides additional data on the favorable role of aspirin on IA and CRC risks and supports the hypothesis of an involvement of intestinal bacterial translocation to the bloodstream.
已有研究表明肠道微生物群参与了阿司匹林对肠腺瘤（IA）和结直肠癌（CRC）的潜在作用。为了进一步研究这个问题，我们分析了一项意大利病例对照研究的数据，该研究包括100例组织学确诊的新发CRC病例，以及100例IA患者和100例结肠镜检查无病变的对照，根据中心、性别和年龄与病例进行匹配。通过酶联免疫吸附测定试剂盒评估血清zonulin水平，通过定量聚合酶链反应和16S rRNA基因谱分析评估血液细菌DNA。58名受试者（19.3%）报告为预防心血管疾病服用阿司匹林≥100毫克/天至少六个月。为了评估阿司匹林与IA和CRC风险之间的关系，使用以匹配变量为条件的逻辑回归模型，并对教育程度进行调整，以及对包括体重指数和心血管疾病在内的几个潜在混杂因素进行调整的模型，估计IA和CRC的比值比（OR）以及阿司匹林使用的相应95%置信区间（CI）。我们通过秩和检验和卡方检验评估了阿司匹林使用者与非使用者之间zonulin水平和细菌DNA数据是否存在差异。使用阿司匹林与IA风险降低（OR = 0.45，95%CI = 0.21 - 0.94）和CRC风险降低（OR = 0.43，95%CI = 0.19 - 0.96）相关。使用完全调整模型获得了类似结果。我们发现，总体上以及在病例组和对照组中，阿司匹林使用者的血液细菌群落属和可操作分类单元（OTU）丰富度低于非使用者。根据阿司匹林使用情况，丙酸杆菌属、鞘氨醇单胞菌属、盖氏菌属、代尔夫特菌属和罗姆布茨菌属、微丝菌目和δ-变形菌纲有所不同。本研究提供了关于阿司匹林对IA和CRC风险有利作用的更多数据，并支持肠道细菌易位至血液参与其中的假说。
