宫颈细胞学异常妇女不同HPV16感染状态下阴道菌群特征及功能分析  

Characteristics and function analysis of vaginal microbiota in women with cervical cytology abnormalities under different HPV16 infection status

作　　者：王嘉浩 张明璇 张乐 宋丽 丁玲 裴蕊欣 闫佳欣 武彩红 吕元婧 崔萌 王志莲[2] 王金桃 WANG Jia-hao;ZHANG Ming-xuan;ZHANG Le;SONG Li;DING Ling;PEI Rui-xin;YAN Jia-xin;WU Cai-hong;LYU Yuan-jing;CUI Meng;WANGZhi-lian;WANG Jin-tao(Department of Epidemiology,School of Public Health,Shanxi Medical University,Taiyuan 030001,China;Department of Obstetrics and Gynecology,Second Hospital of Shanxi Medical University,Taiyuan 030001,China)

机构地区：[1]山西医科大学公共卫生学院流行病学教研室,太原030001 [2]山西医科大学第二医院妇产科,太原030001

出　　处：《中华疾病控制杂志》2023年第3期268-273,325,共7页Chinese Journal of Disease Control & Prevention

基　　金：国家自然科学基金(81872705)。

摘　　要：目的 探讨宫颈细胞学异常妇女不同HPV16感染状态下阴道菌群的特征,并对菌群功能进行预测。方法 选取2018年1―6月在山西医科大学第二医院妇科门诊经液基薄层细胞学检查(liquid-based thinprep cytologic test, TCT)宫颈细胞学异常的132例妇女为研究对象,利用导流杂交法进行HPV感染及分型检测,采集阴道分泌物进行16S rDNA测序,利用生物信息学方法描述阴道菌群特征,并结合Kyoto Encyclopedia of Genes and Genomes(KEGG)数据库对阴道菌群功能进行分析。结果 HPV16阳性妇女(59例)Simpson指数低于阴性妇女(73例)(P=0.047),而Shannon指数高于阴性妇女(P=0.036),基于Bray-Curtis距离的非度量多维尺度分析(non-metric multidimensional scaling, NMDS)显示两组Beta多样性差异无统计学意义(P=0.199)。宫颈细胞学异常妇女以及不同HPV16感染状态下均以乳酸杆菌为优势菌,但在HPV16阳性组乳酸杆菌占比降低(57.50%vs.60.69%),加德纳菌属(14.29%vs.13.66%)、嗜胨菌属(4.28%vs.2.99%)等厌氧菌属的构成比增加。在HPV16阴性组中乳酸杆菌属、肠球菌属、葡萄球菌属等丰度均高于阳性组,而HPV16阳性组中加德纳菌属、解脲脲原体、嗜胨菌属、普雷沃菌属等厌氧菌的丰度则均高于阴性组。Linear discriminant analysis Effect Size(LEfSe)软件分析显示解脲脲原体、嗜胨菌属为HPV16阳性组的特征菌。功能分析显示阴道菌群的功能主要集中在代谢层面,在HPV16阳性组以破坏阴道微环境和促进恶性肿瘤发生为主,HPV16阴性组以抑癌作用和糖脂代谢为主。结论 阴道菌群多样性增加、比例结构改变与HPV16感染密切相关,解脲脲原体、嗜胨菌属可作为HPV16感染的潜在生物标志,HPV16感染状态下阴道菌群可能具有引发阴道微环境紊乱和促癌的功能。Objective To explore the characteristics of vaginal microbiota in women with abnormal cervical cytology under different HPV16 infection status, and to predict the function of the vaginal microbiota. Methods A total of 132 women with abnormal cervical cytology by liquid-based thinprep cytologic test(TCT), who came from the gynecological clinic of Second Hospital of Shanxi Medical University during January to June 2018, were enrolled in this study. Flow-through Hybridization technology was used to determine HPV infection typing. The vaginal microbiota was detected by 16S rDNA sequencing. The characteristic of vaginal microbiota were described by bio informatics, and Kyoto Encyclopedia of Genes and Genomes(KEGG) database was used to analyze the function of the vaginal microbiota. Results The Simpson index in the HPV16 positive group(n=59) was lower than that in the negative(n=73) group(P=0.047), while the Shannon index was higher in the positive group(P=0.036). Non-metric multidimensional scaling(NMDS) based on Bray-Curtis dissimilarities showed that there was no significance in Beta diversity between the two groups(P=0.199). Lactobacillus was the dominant bacteria in women with abnormal cervical cytology and different HPV16 infection status, but the proportion of Lactobacillus decreased(57.50%vs.60.69%) and anaerobic bacteria such as Gardnerella(14.29%vs.13.66%), and Peptoniphilus(4.28%vs.2.99%) increased in the HPV16 positive group. The abundance of Lactobacillus, Enterococcus, Staphylococcus and so on in the negative group was higher than that in the positive group, while the abundance of anaerobic bacteria such as Gardnerella, Ureaplasma, Peptoniphilus, Prevotella and so on in the HPV16 positive group was higher than that in the negative group. Ureaplasma and Peptoniphilus were the characteristic bacteria in HPV16 positive women based on Linear discriminant analysis Effect Size(LEfSe) analysis. The functional analysis showed that the function of vaginal microbiota was mainly concentrated on metabolism. The vagin

关 键 词：宫颈细胞学异常 人乳头瘤病毒16型 阴道菌群 16S rDNA测序 功能预测 

分 类 号：R589.7[医药卫生—内分泌]