不同宫颈病变女性阴道菌群特征变化及菌群间相互关系分析

The characteristics and correlations of vaginal flora in women with cervical lesions

目的探讨不同宫颈病变女性阴道菌群的特征变化及菌群间的相互关系。方法选取2018年1—6月于山西医科大学第二医院就诊、经病理学确诊宫颈病变的女性,其中正常宫颈(NC)41例,低度宫颈上皮内瘤样变(CIN 1)39例,高度宫颈上皮内瘤样变(CIN 2/3)37例,宫颈鳞状细胞癌(SCC)15例。应用16S rDNA测序技术对阴道分泌物中的阴道菌群进行检测,采用共生网络分析菌群间的Spearman相关关系。结果NC、CIN 1和CIN 2/3患者优势菌均为乳酸杆菌属[构成比分别为79.4%(1869598/2354098)、63.6%(1536466/2415100)和58.3%(1342896/2301536)],嗜胨菌属[20.4%(246072/1205154)]为SCC患者的优势菌。随着宫颈病变的加重,阴道菌群多样性呈升高趋势(Shannon指数F=6.39,P=0.001;Simpson指数F=3.95,P=0.012),乳酸杆菌属构成比逐渐降低,嗜胨菌属、纤毛菌属、普雷沃菌属等厌氧菌构成比逐渐增加,特征菌(LDA分值>3.5)由乳酸杆菌属演变为以嗜胨菌属、拟杆菌属、卟啉单胞菌属等为代表的厌氧菌。选取相对丰度居前10位、Spearman相关系数>0.4且P<0.05的菌属经共生网络分析,结果显示,在不同阶段宫颈病变组中,普雷沃菌属、嗜胨菌属、卟啉单胞菌属、厌氧球菌属、纤毛菌属、奇异菌属、加德纳菌属、链球菌属等厌氧菌属之间呈正相关,而乳酸杆菌属与多种厌氧菌属呈负相关,尤其在CIN 1患者中阴道菌群间关系最为复杂,在SCC患者中仅嗜胨菌属与乳酸杆菌呈负相关。结论阴道菌群多样性增加、菌群间相互关系改变与宫颈病变密切相关,嗜胨菌属对宫颈病变的诊断及预测预警具有重要意义。

Objective To explore the characteristics and correlations of vaginal flora in women with cervical lesions.Methods A total of 132 women,including 41 women diagnosed with normal cervical(NC),39 patients with low-grade cervical intraepithelial neoplasia(CIN 1),37 patients with high-grade cervical intraepithelial neoplasia(CIN 2/3)and 15 patients with cervical squamous cell carcinoma(SCC),who came from the gynecological clinic of Second Hospital of Shanxi Medical University during January 2018 to June 2018,were enrolled in this study according to the inclusive and exclusive criteria strictly.The vaginal flora was detected by 16S rDNA sequencing technology.Co-occurrence network analysis was used to investigate the Spearman correlations between different genera of bacteria.Results The dominant bacteria in NC,CIN 1 and CIN 2/3 groups were Lactobacillus[constituent ratios 79.4%(1869598/2354098),63.6%(1536466/2415100)and 58.3%(1342896/2301536),respectively],while Peptophilus[20.4%(246072/1205154)]was the dominant bacteria in SCC group.With the aggravation of cervical lesions,the diversity of vaginal flora gradually increased(Shannon index:F=6.39,P=0.001;Simpson index:F=3.95,P=0.012).During the cervical lesion progress,the ratio of Lactobacillus gradually decreased,the ratio of other anaerobes such as Peptophilus,Sneathia,Prevotella and etc.gradually increased,and the differential bacteria(LDA score>3.5)gradually evolved from Lactobacillus to other anaerobes.The top 10 relative abundance bacteria,spearman correlation coefficient>0.4 and P<0.05 were selected.Co-occurrence network analysis showed that Prevotella,Peptophilus,Porphyrinomonas,Anaerococcus,Sneathia,Atopobium,Gardnerella and Streptococcus were positively correlated in different stages of cervical lesions,while Lactobacillus was negatively correlated with the above anaerobes.It was found that the relationship between vaginal floras in CIN 1 group was the most complex and only Peptophilus was significantly negatively correlated with Lactobacillus in SCC group.Conclusions The increased diversity and changed correlations between vaginal floras are closely related to cervical lesions.Peptophilus is of great significance in the diagnosis,prediction and early warning of cervical carcinogenesis.