并发不孕的子宫内膜异位症患者阴道菌群的微生物组学研究

The Microbiome Study of Vaginal Bacteria in Endometriosis Patients with Infertility

目的:探讨子宫内膜异位症(EMs)患者人群中是否合并不孕患者的微生物组学差异,并找出相关的差异细菌和微生物学标识。方法:选取2018年4月2019年9月于中国医学科学院北京协和医院妇产科手术诊断为EMs的患者66例,按是否合并不孕分为不孕组(n=17)和对照组(n=49),通过对于阴道后穹窿分泌物细菌16S核糖体RNA(16S-rRNA)测序结合生物信息学分析,使用细菌群落多样性算法(alpha多样性、beta多样性)、主坐标分析(PCoA)距离矩阵算法(Bray-Curtis和Unifrac矩阵)、生物学标识算法(LeFSe)找出含量有差异的细菌物种。结果:2组患者的细菌群落在alpha多样性中未见显著差异,在beta多样性中可观察到不孕组的乳酸杆菌含量略有减少。有3种细菌属表现出了显著的统计学差异,分别是普氏菌属(Prevotella)、巨型球菌属(Megasphere)和小类杆菌属(Dialister),其在不孕组患者中明显升高。PCoA矩阵分析未表现出显著的差异。变形菌门(Proteobacteria)和γ-变形菌纲(Gammaproteobacteria)可能是潜在的生物学标识物。结论:在EMs患者中,是否合并不孕与下生殖道细菌群落差异有关,细菌丰度的变化可能用来评估宿主的免疫水平与EMs不孕患者症状差异,为今后EMs不孕的机制研究和微生物诊断学发展奠定了理论学基础。

Objective:The purpose of this study was to investigate the microbiome differences in endometriosis(EMs)patients with infertility and to identify the relevant differential bacteria and microbiological biomarkers.Methods:This study was conducted in Chinese Academy of Medical Science Peking Union Medical College Hospital form April 2018 to September 2019,66 patients with EMs were selected and their final diagnose were obtained by surgical report.They were divided into infertility group(n=17)and control group(n=49).Vaginal posterior fornix was the sampling site.After bacterial 16S-rRNA sequencing and bioinformatics analysis,bacteria community diversity algorithm(alpha,beta),PCoA distance matrix algorithm(Bray-Curtis and Unifrac matrix)and biological identification algorithm(LeFSe)were used to analyze the compositional difference of bacteria.Results:There was no significant difference in alpha diversity in the bacterial community between the two groups,while the content of Lactobacillus in the infertile group was slightly decreased in beta diverisity.Three kinds of bacteria showed significant statistical differences,Prevotella,Megasphere and Dialister,which were significantly increased in infertile patients.PCoA showed no significant difference.Proteobacteria at the phylum level and Gammaproteobacteria at the class level are underlying biomarkers.Conclusions:This study revealed that in EMs patients,whether infertility is associated with differences in the bacterial community in the lower reproductive tract,and changes in bacterial abundance may be used to assess differences in host immunity and symptoms in EMs infertility patients.It also played an important role in the study of mechanisms of EMs and the development of microbial diagnostics.