艾塞那肽治疗多囊卵巢综合征患者引起肠道菌群的改变  

Gut microbiome alterations after exenatide treatment in patients with polycystic ovary syndrome

作　　者：马瑞琳 邓燕[1] 孙爱军[1] MA Rui-lin;DENG Yan;SUN Ai-jun(Department of Obstetrics&Gynecology,Peking Union College Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College,National Clinical Research Center for Obstetric&Gynecologic Diseases,Beijing 100730)

机构地区：[1]中国医学科学院北京协和医学院北京协和医院妇产科,国家妇产疾病临床研究中心,北京100730

出　　处：《生殖医学杂志》2021年第7期937-945,共9页Journal of Reproductive Medicine

基　　金：国家自然科学基金(82074143)。

摘　　要：目的探讨艾塞那肽治疗对超重/肥胖多囊卵巢综合征(PCOS)患者肠道菌群的影响。方法34例超重/肥胖PCOS患者按1∶1比例随机分为两组,分别接受艾塞那肽联合二甲双胍(联合组)或单独二甲双胍(单药组)治疗12周,使用无菌粪便标本管收集两组患者治疗前后的新鲜粪便标本,利用16S rRNA测序技术进行肠道菌群分析。结果两组患者治疗后体重和糖化血红蛋白水平均显著下降(P<0.05)。联合组患者治疗后空腹血糖和75 g口服葡萄糖耐量试验(OGTT)-2 h血糖亦显著下降(P<0.05)。肠道菌群α多样性分析发现Chao指数在两组患者中组间及组内均无显著差异(P>0.05);Shannon指数在单药组无显著变化(P>0.05),在联合组呈下降趋势但变化不显著(P>0.05)。主坐标分析(PCoA)发现联合组治疗显著改变了超重/肥胖PCOS患者肠道菌群的物种组成结构(P<0.05),单药组无显著改变(P>0.05)。联合组治疗后厚壁菌门、拟杆菌门和绿弯菌门丰度显著降低,变形菌门丰度显著增加(P<0.05)。单药组治疗后粪杆菌属丰度显著增加(P<0.05)。联合组拟杆菌门/厚壁菌门比值在治疗后显著低于治疗前[(0.01±0.02)vs.(0.05±0.07),P=0.01],单药组则无显著变化[(0.04±0.06)vs.(0.05±0.06),P=0.26]。结论艾塞那肽可以调节超重或肥胖PCOS患者肠道菌群的结构和物种组成,降低微生物多样性,且与二甲双胍对肠道菌群的影响不同。肠道菌群可能是药物发挥作用的一个靶点。Objective:To explore the effect of exenatide treatment on gut microbiota in overweight/obese patients with polycystic ovary syndrome(PCOS).Methods:Thirty-four overweight/obese PCOS women were randomized to two treatment groups at a ratio of 1∶1:metformin alone(MET group)or metformin combined with exenatide(COM group),receiving the treatment for 12 weeks.Fresh fecal samples of the two groups before and after treatment were collected using sterile fecal tube,and 16S rRNA sequencing technology was used to analyze the gut microbiota.Results:Body weight and HbA1c levels were significantly decreased after treatment in both groups(P<0.05).Additionally,the levels of fasting glucose and 75 g oral glucose tolerance test(OGTT)-2 hours glucose were significantly decreased in COM group(P<0.05).Gut microbiotaαdiversity analysis showed that there was no significantly difference in Chao index before and after treatment and between the two groups(P>0.05).Shannon index showed no significant change in the MET group(P>0.05).There was a downward trend in the COM group,but the change was not significant(P>0.05).The PCoA score plots showed that the species composition of gut microbiota in overweight/obese PCOS patients was significantly changed in the COM group(P<0.05),but not in MET group(P>0.05).Metformin combined with exenatide therapy significantly decreased the abundance of Firmicutes,Bacteroidetes and Chloroflexi,and increased the abundance of Proteobacteria(P<0.05).MET therapy significantly increased the abundance of Faecalibacterium(P<0.05).The ratio of Bacteroidetes/Firmicutes after treatment was significantly lower than before treatment in the COM group[(0.01±0.02)vs.(0.05±0.07),P=0.01],but there was no significant change in the MET group[(0.04±0.06)vs.(0.05±0.06),P=0.26].Conclusions:Exenatide can change the gut microbiota structure and species composition and reduce microbial diversity in overweight/obese patients with PCOS,and the effect of exenatide on gut microbiota is different from metformin.Gut microbiota may be

关 键 词：多囊卵巢综合征 肠道菌群 艾塞那肽 二甲双胍 

分 类 号：R711.75[医药卫生—妇产科学]