维生素D对肠道菌群结构及结直肠癌发病风险的影响

Effects of Vitamin D on the risk of colorectal cancer by affecting intestinal flora structure

目的探讨维生素D对肠道菌群结构及结直肠癌的发病风险的影响。方法选择清洁级健康雄性Wistar大鼠45只,将大鼠随机分为3组,每组15只。对照组大鼠正常饲养,模型组、干预组大鼠建立结直肠癌动物实验模型后,模型组大鼠给予生理盐水灌胃,干预组给予维生素D灌胃。分别在2、4、6、10周时检测大鼠体质量变化,比较3组大鼠结直肠成瘤率及肿瘤数目,粪便菌群及结直肠黏膜中菌落分布情况和OTU丰度变化,以及结直肠癌相关微小RNA(miRNA)表达水平、波形蛋白(Vimentin)表达水平。结果从第4周开始,模型组与干预组大鼠体质量明显低于对照组,差异有统计学意义(P<0.05)。模型组与干预组大鼠成瘤率均为100%,但模型组肿瘤数量[(7.68±1.89)个]明显高于干预组[(2.79±0.51)个],差异有统计学意义(t=9.675,P<0.001)。与对照组相比,模型组粪便菌群中拟杆菌门明显升高,放线菌门、厚壁菌门明显降低(P<0.05);与模型组相比,干预组拟杆菌门数量明显降低,厚壁菌门数量明显升高(P<0.05)。与对照组相比,模型组结直肠黏膜菌群中放线菌门、拟杆菌门明显升高,厚壁菌门、梭杆菌门明显降低(P<0.05)。与对照组相比,模型组粪便菌群及结直肠黏膜菌群OTU丰度明显升高(P<0.05);与模型组相比,干预组粪便菌群及结直肠黏膜菌群OTU丰度明显降低(P<0.05)。与对照组相比,模型组大鼠结肠组织miRNA-155、miRNA-21a水平明显升高(P<0.05);与模型组相比,干预组miRNA-155水平明显降低(P<0.05)。与对照组相比,模型组Vimentin水平明显升高(P<0.05);与模型组相比,干预组Vimentin蛋白水平明显下降(P<0.05)。结论维生素D可能通过影响肠道菌群结构、降低Vimentin水平进而降低结直肠癌的发病风险。

Objective To analyze the effect of vitamin D on the risk of colorectal cancer by affecting intestinal flora structure.Methods Forty-five healthy male Wistar rats of clean grade were selected,and divided into three groups,15 rats in each group.The rats in model group and intervention group were used to establish an experimental model of colorectal cancer.The rats in control group were given normal feeding,model group were given drinking water containing physiological saline solution,and intervention group were given vitamin D.W eight changes,colorectal tumorigenesis rate,number of tumors,distribution of faecal flora,colonies in colorectal mucosa and OTU abundance were measured at 2,4,6 and 10 weeks,respectively.The effects of vitamin D on the expression of colorectal cancer-related genes and the expression of Vimentin protein in colorectal tissues were also examined.Results From the 4th week,the body weight of the model group was significantly lower than that of the control group(P<0.05).The tumorigenesis rate of model group and intervention group was 100%,but the number of tumors in model group(7.68±1.89)was significantly higher than that in intervention group(2.79±0.51),difference was statistically significant(t=9.675,P<0.001).Compared with the control group,the number of Bacteroides in the model group were significantly higher,while Firmicutes and Actinomycetes were significantly lower(P<0.05).Compared with the model group,the number of Bacteroides in the intervention group was significantly lower and the number of Firmicutes was significantly higher(P<0.05).Compared with the control group,the number of Actinomycetes and Bacteroides in the model group was significantly higher while the number of Firmicutes and F usobacteria was significantly lower(P<0.05).Compared with the control group,the OTU abundance of fecal flora and colonic mucosa flora in the model group was significantly higher(P<0.05).Compared with the model group,the OTU abundance of fecal flora and colonic mucosa flora in the intervention group was significantly lower(P<0.05).Compared with the control group,the levels of microRNA-155 and microRNA-21a in the colon tissue of the model group increased significantly(P<0.05).Compared with the model group,the levels of microRNA-155 in the intervention group decreased significantly(P<0.05).Compared with the control group,the level of Vimentin in the intervention group was significantly higher(P<0.05).And the level of Vimentin in the model group was significantly lower than that of model group(P<0.05).Conclusion Vitamin D may reduce the risk of colorectal cancer by affecting intestinal flora structure and reducing Vimentin protein level.