多囊卵巢综合征伴胰岛素抵抗患者肠道菌群分析

目的基于16S rRNA高通量测序技术对多囊卵巢综合征(PCOS)伴胰岛素抵抗(IR)患者肠道菌群的结构特征进行分析。方法选择2019年7月至2020年6月期间就诊于青岛大学附属烟台毓璜顶医院的新发PCOS女性,根据稳态模型胰岛素抵抗指数(HOMA-IR)分为IR-PCOS组(n=11)和NIR-PCOS组(n=10)。选择同期在毓璜顶医院体检中心行孕前检查的年龄匹配且排卵正常的女性为对照组(HC组,n=11)。对所有研究对象进行直肠拭子取样,扩增细菌的16S rRNA V3-V4片段然后对其进行测序,分析各组对象肠道菌群的组成特征及其与临床参数之间的相关性。结果相较于健康女性,PCOS患者肠道菌群结构发生了显著改变,表现为多样性降低(P<0.05),菌群中拟杆菌门相对丰度显著高于HC组(P<0.001),厚壁菌门显著减少(P<0.01);IR-PCOS组患者肠道菌群多样性降低程度显著大于NIR-PCOS组患者(P<0.05),拟杆菌门相对丰度也显著高于NIR-PCOS组患者(P<0.001)。菌群中弯曲杆菌、拟杆菌门、脱硫杆菌门和睾酮、黄体生成素、黄体生成素与卵泡刺激素之比、体质量指数、胰岛素抵抗指数、肿瘤坏死因子、血脂紊乱程度呈正相关,而变形菌门、放线菌门和绿弯菌门则与之呈负相关,其中弯曲杆菌和黄体生成素与卵泡刺激素之比、变形菌门和体质量指数、绿弯菌门和血清总胆固醇之间的相关性有统计学意义(P<0.05)。结论PCOS伴IR患者肠道菌群紊乱更加明显,肠道菌群失调可能是加重PCOS患者代谢异常的原因之一。

Analysis of intestinal microbiota in patients with polycystic ovary syndrome and insulin resistance

Objective:To analyze the composition characteristics of the intestinal microbiota in the patients with polycystic ovary syndrome(PCOS)and insulin resistance(IR)by using 16 S rRNA high-throughput sequencing technology.Methods:The women with newly diagnosed PCOS were divided into IR-PCOS group(n=11)and NIR-PCOS group(n=10)according to homeostasis model insulin resistance index(HOMA-IR)in Yantai Yuhuangding Hospital from July 2019 to June 2020.The health control group(HC group,n=11)was age-matched women with normal ovulation who underwent pre-pregnancy examination in the physical examination center of Yuhuangding Hospital during the same period.Rectal swabs were taken from all subjects to amplify and sequence the bacterial 16 S rRNA V3-V4 fragments,and analyze the composition characteristics of the intestinal microbiota and the correlation with clinical parameters.Results:The composition of intestinal microbiota in PCOS patients was significant changed and manifested as decreased diversity(P<0.05).The relative abundance of bacteroides in the flora was significantly higher than that in the healthy group(P<0.001),and firmicutes were significantly reduced(P<0.01).The diversity of intestinal microbiota in the IR-PCOS group was significant lower than that in the NIR-PCOS group(P<0.05).The relative abundance of bacteroides in the IR-PCOS group was significantly higher than that in the NIR-PCOS group(P<0.001).Campilobacterota,bacteroides and desulfobacterium in the flora were positively correlated with testosterone,LH,LH/FSH,BMI,insulin resistance index,tumor necrosis factor,and degree of dyslipidemia,while proteobacteria,actinobacteria and chloroflexi were the opposite.There was significant correlation between campilobacterota and LH/FSH,proteobacteria and BMI,chloroflexi and serum total cholesterol(P<0.05).Conclusions:Intestinal microbiota disorders are more obvious in patients with IR-PCOS,and it may be one of the reasons that aggravate abnormal metabolism in PCOS patients.