高脂饮食诱导的子宫内膜不典型增生小鼠肠道菌群微生物组学研究  

Changes of Gut Microbiome in Mice with Uterus Endometrial Atypical Hyperplasia Induced by High Fat Diet

作　　者：李艳辉 赵蓉 肖诚瑀 汪宏波[1] Li Yanhui;Zhao Rong;Xiao Chengyu(Department of Obstetrics and Gynecology Union Hospital,Tongji Medical College,Huazhong University of Science and Technology Wuhan 430022,China)

机构地区：[1]华中科技大学同济医学院附属协和医院妇产科,武汉430022

出　　处：《华中科技大学学报（医学版）》2022年第2期139-145,共7页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：国家自然科学基金资助项目(No.81701423)。

摘　　要：目的探讨高脂饮食构建的小鼠子宫内膜不典型增生模型中肠道微生物群的改变,并进行功能预测分析。方法6周龄CD-1雌性小鼠随机分为正常热量饮食组(对照组)、高脂饮食组(HFD组)及17-β雌二醇干预组(E2干预组),分组处理26周。苏木精-伊红染色鉴定各组小鼠子宫内膜病变发生情况;小鼠粪便行宏基因组学测序,采用生物信息学方法对肠道微生物群测序数据进行分析。结果HFD组小鼠子宫内膜均出现增生改变,且其子宫内膜不典型增生发生率与E2干预组小鼠相似(16.7%vs.25.0%,P=0.61);与对照组比较,HFD组的肠道微生物群α多样性指标Shannon指数呈升高趋势,但差异无统计学意义(P=0.2667);与对照组肠道微生物群在门水平进行比较,HFD组的拟杆菌门(Bacteroidetes)丰度显著降低,而厚壁菌门(Firmicutes)丰度显著增高(均P<0.05);在属和种水平上,与对照组相比,HFD组肠道微生物群Prevotella属(12.800%vs.3.395%)和Clostridium属(9.081%vs.6.613%)的相对丰度降低,而脆弱拟杆菌种(Bacteroides fragilis)相对丰度显著升高。功能预测发现氧化磷酸化、铁死亡、凋亡等基因在HFD组富集。结论高脂饮食诱导下的子宫内膜不典型增生小鼠存在肠道微生物群的失调,肠道微生物群的改变可能参与并促进了子宫内膜增生甚至癌变。Objective To investigate the changes in gut microbiome in mice with uterus endometrial atypical hyperplasia induced by high fat diet and to predict the gene function of the flora.Methods Six-week-old female CD-1 mice were randomly divided into normal calorie diet group,high fat diet(HFD)group and 17-βestradiol(E2)intervention group.Group intervention lasted for 26 weeks.HE staining slices were used to observe the endometrial lesions in each group.Metagenomic sequencing was performed on the feces of mice,and bioinformatics analysis were implemented in the sequencing data of gut microbiome.ResultsEndometrial atypical hyperplasia was observed in HFD group,and the incidence was similar between HFD group and E2 group(16.7%vs.25.0%,P=0.61).Compared with the control group,αdiversity index(Shannon index)in HFD group was higher than that in the control group,but the difference was not statistically significant(P=0.2667).Compared with the control group at phylum level,the relative abundance of Bacteroidetes in the HFD group was significantly decreased,while the relative abundance of Firmicutes was significantly increased(both P<0.05).At the genus and species level,the relative abundance of Prevotella(12.800%vs.3.395%)and Clostridium(9.081%vs.6.613%)were decreased in HFD group.The relative abundance of Bacteroides fragilis was increased significantly.Functional prediction showed that oxidative phosphorylation,ferroptosis and apoptosis genes were enriched in HFD group.Conclusion Dysbiosis of gut microbiome could be observed in mice with uterus endometrial atypical hyperplasia induced by high fat diet,which may lead to endometrial hyperplasia and even cancer.

关 键 词：子宫内膜不典型增生 肠道微生物群 高脂饮食 肥胖 宏基因组测序 

分 类 号：R711.74[医药卫生—妇产科学]