维生素D调节炎症元素、细胞分化和增殖以及益生菌在肠道微生物群和免疫应答中的作用，引起了人们对两者在结直肠肿瘤化疗和化学预防中的应用的兴趣。本研究旨在研究维生素D3和益生菌的单独和/或联合治疗对结直肠癌形成的影响。使用1,2-二甲基肼诱导Wistar大鼠的结肠发生癌前病变，分别采用三种不同的方法（同时、预处理和后处理）给予益生菌和/或维生素D治疗。我们通过免疫组织化学和RT-PCR测定频率的变异隐窝病灶（ACF）和变异隐窝（AC）、粪便微生物组成、基因和蛋白质表达以及水消耗和体重监测来评估它们的效果。结果确认了治疗的全身安全性，并显示了维生素D和益生菌在所有方案中及联合治疗中的保护作用，不同于对照组的优势细菌门类。治疗组显示出不同水平的Nrf2、GST、COX2、iNOS、β-连接蛋白和PCNA表达。这些实验条件探索了维生素D和益生菌在结直肠癌发生的不同阶段涉及的途径上低剂量的补充剂的结合，结果支持其在预防和长期策略中的应用。版权所有©2023年。由Elsevier Inc.出版。

The modulation of inflammatory elements, cell differentiation and proliferation by vitamin D and the role of probiotics in the intestinal microbiota and immunogenic response have sparked interest in the application of both in chemotherapeutics and chemoprevention of colorectal tumors.The present study aimed to investigate the effects of isolated and/or combined treatment of vitamin D3 and probiotics on colorectal carcinogenesis.Pre-neoplastic lesions were induced with 1,2-dimethylhydrazine in the colon of Wistar rats, which were treated with probiotics and/or vitamin D in three different approaches (simultaneous, pre-, and post-treatment). We investigated the frequency of aberrant crypt foci (ACF) and aberrant crypt (AC) in the distal colon, fecal microbiome composition, gene and protein expression through immunohistochemical and RT-PCR assays, and general toxicity through water consumption and weight gain monitoring.Results confirm the systemic safety of treatments, and show a protective effect of vitamin D and probiotics in all approaches studied, as well as in combined treatments, with predominance of different bacterial phyla compared to controls. Treated groups show different levels of Nrf2, GST, COX2, iNOS, β-catenin and PCNA expression.These experimental conditions explore the combination of vitamin D and probiotics supplementation at low doses over pathways involved in distinct stages of colorectal carcinogenesis, with results supporting its application in prevention and long-term strategies.Copyright © 2023. Published by Elsevier Inc.