二甲双胍调控肠道菌群并抑制结直肠癌的生长

Metformin regulates gut microbiota and inhibits the growth of colorectal cancer

目的探究二甲双胍抑制肠癌的生长及调控肠道菌群的作用。方法 20只C57BL/6J小鼠通过AOM-DSS诱导结直肠癌发生,分成2组每天分别灌胃生理盐水及二甲双胍溶液,12周后处死小鼠,收集结直肠组织及粪便,比较2组小鼠肠道肿瘤个数及大小并进行H&E染色分析,运用16S rRNA基因测序技术检测小鼠肠道菌群组成,使用QIIME软件分析菌群物种分类、物种多样性指数及组间显著性差异。结果 2组小鼠体质量随周龄增加均呈现增长趋势,且实验结束时体质量差异无统计学意义(t=0.743 1,P=0.469 7)。与对照组相比,接受二甲双胍灌胃的实验组小鼠结直肠肿瘤数量减少(t=2.260 0,P=0.040 3)且尺寸偏小(t=2.570 0,P=0.014 4)。粪便菌群测序结果显示实验组小鼠肠道菌群丰富度增加(P<0.05),而在多样性方面差异无统计学意义(P>0.05)。在属水平上,实验组Akkermansia、Ruminococcus及ClostridiumⅩⅣa和Ⅳ等细菌的丰富度增加。结论二甲双胍能够调控肠道菌群的组成,增加肠道内产SCFAs细菌的定植,并抑制肠癌的发生发展。

Objective To explore the role of Metformin in inhibiting the growth of colorectal cancer and regulating gut microbiota. Methods Colorectal cancer was induced with AOM-DSS in 20 C57 BL/6 J mice. The mice were divided into two groups and gavaged with saline and metformin solution every day,respectively. After 12 weeks, the mice were sacrificed to collect colorectal tissue and feces.The number and size of intestinal tumors in the two groups were compared and H&E staining analysis was performed. 16 S rRNA gene sequencing technology was used to detect the composition of the mouse fecal microbiota, and QIIME software were used to analyze the classification and diversity index of gut microbiota, and the significant differences between two groups. Results The weight of the mice in the two groups showed an increasing trend with increasing age, with no significant difference at the end of the experiment(t=0.743 1, P=0.469 7). Compared with the control group, the number of colorectal tumors in the observation group which received gavage of metformin was reduced(t=2.260 0, P=0.040 3) and the size was smaller(t=2.570 0, P=0.014 4), which was significantly different.Sequencing of fecal microbiota showed that the abundance of microbiota in the observation group increased(P<0.05), but there was no significant difference in diversity(P>0.05). At the genus level, the abundance of bacteria such as Akkermansia, Ruminococcus, Clostridium ⅩⅣa and Clostridium Ⅳ increased in the observation group. Conclusion Metformin can regulate the composition of intestinal microbiota and increase the colonization of SCFAs-producing bacteria in the intestine, and inhibiting the development of colorectal cancer.