阴道微生物多样性与高危型HPV感染的相关性研究

Study on the relationship between vaginal microbiota and cervical high risk human papillomavirus infection

目的:探讨阴道微生物多样性与宫颈高危型HPV(hr HPV)感染的相关性。方法:选取于上海交通大学医学院附属仁济医院体检中心体检或社区募集的68例HPV阴性妇女(正常组)和75例hr HPV感染妇女(感染组)。采用16S rRNA基因扩增技术和二代高通量测序技术分析其阴道微生物组成。结果:两组妇女阴道微生物在门水平,均以厚壁菌门为主要物种,但与正常组(73.23%)相比,感染组(68.77%)所占比例下降。与正常组相比,感染组放线菌门所占比例亦下降,而变形菌门和无壁菌门所占比例明显升高。在种水平,两组均以乳杆菌为主要菌群,其中惰性乳杆菌为优势菌群,在正常组、感染组的比例分别为41.41%、28.03%,其次为阴道加德纳菌。与正常组相比,感染组惰性乳杆菌和阴道加德纳菌所占比例呈下降趋势;而芽孢杆菌、普氏菌、巨球菌、纤毛球菌、链球菌所占比例呈上升趋势。与正常组相比,感染组物种丰富度指数Sobs指数、Ace指数均升高,物种多样性指数Shannon指数升高,Simpson指数降低,差异有统计学意义。利用LEf Se及LDA判别分析两组特征意义的物种,芽孢杆菌、志贺杆菌、海洋杆菌可作为感染组的生物标记物种,乳杆菌、加德纳菌、阴道奇异菌为正常组的生物标记物种。结论:上海地区高危HPV感染女性具有阴道微生物菌群多样性和丰富度增加,乳杆菌水平减少的特点,芽孢杆菌、志贺杆菌和海洋杆菌可作为其生物标记物种,为临床今后从调节阴道微生态角度治疗高危HPV感染提供理论依据。

Objective： To investigate the correlationship between vaginal microbiota and cervical high-risk HPV infection.Methods： Healthy women were recruited from the Physical Examination Center of Renji Hospital or from the community to detect their cervical HPV infection and vaginal microbiota. According to the HPV infection status,they were divided into two groups： normal group、hr HPV infected group. Vaginal bacterial communities were characterized by pyrosequencing of barcoded 16 S rRNA genes. The next generation sequencing was used to detect vaginal microbiota. Bioinformatics analysis methodes were used to evaluate the correlationship.Results： There were 68 samples in normal group and 75 samples in the infected group.Lactobacillus was dominant in both groups,and the number of lactobacilli in infected group was decreased,while there was no statistical difference. Bacillus,Shigella,Prevotella,Megasphaera etc.were increased in infected group,the differences were statistically significant.Compared with the normal group,the species richness index Sobs and ACE were increased,the species diversity index Shannon increased,Simpson decreased,the differences were statistical significance. LEf Se and LDA discriminant analysis were used to define the characteristics biomarkers of the two groups of species.Bacillus,Shigella and Oceanobacillus can be used as the biomarkers for infected group.Lactobacillus,Gardnerella,Atopobium vaginae were normal group biomarker species.Conclusion： Lactobacillus in the vaginal microbiota of hr HPV infection is reduced,and species diversity index and richness index in this group are increased.Bacillus、Shigella 、Oceanobacillus can be regarded as biomarkers species of HPV infection.