Cheng Liqin, Kaźmierczak Dominika, Norenhag Johanna, Hamsten Marica, Fransson Emma, Schuppe-Koistinen Ina, Olovsson Matts, Engstrand Lars, Hydbring Per, Du Juan
Department of Microbiology, Tumor and Cell Biology, Centre for Translational Microbiome Research (CTMR), Karolinska Institutet, Stockholm, Sweden.
Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.
mSystems. 2021 May 4;6(3):e00175-21. doi: 10.1128/mSystems.00175-21.
The vaginal microbiota plays an essential role in vaginal health. The vaginas of many reproductive-age women are dominated by one of the species. However, the vaginas of a large number of women are characterized by the colonization of several other anaerobes. Notably, some women with the non--dominated vaginal microbiota develop bacterial vaginosis, which has been correlated with sexually transmitted infections and other adverse outcomes. However, interactions and mechanisms linking the vaginal microbiota to host response are still under investigation. There are studies suggesting a link between human microRNAs and gut microbiota, but limited analysis has been carried out on the interplay of microRNAs and vaginal microbiota. In this study, we performed a microRNA expression array profiling on 67 vaginal samples from young Swedish women. MicroRNAs were clustered into distinct groups according to vaginal microbiota composition. Interestingly, 182 microRNAs were significantly elevated in their expression in the non--dominated community, suggesting an antagonistic relationship between and microRNAs. Of the elevated microRNAs, 10 microRNAs displayed excellent diagnostic potential, visualized by receiver operating characteristics analysis. We further validated our findings in 34 independent samples where expression of top microRNA candidates strongly separated the -dominated community from the non--dominated community in the vaginal microbiota. Notably, the -dominated community showed the most profound differential microRNA expression compared with the non--dominated community. In conclusion, we demonstrate a strong relationship between the vaginal microbiota and numerous genital microRNAs, which may facilitate a deeper mechanistic interplay in this biological niche. Vaginal microbiota is correlated with women's health, where a non--dominated community predisposes women to a higher risk of disease, including human papillomavirus (HPV). However, the molecular relationship between the vaginal microbiota and host is largely unexplored. In this study, we investigated a link between the vaginal microbiota and host microRNAs in a group of young women. We uncovered an inverse correlation of the expression of microRNAs with the abundance of species in the vaginal microbiota. Particularly, the expression of microRNA miR-23a-3p and miR-130a-3p, displaying significantly elevated levels in non--dominated communities, predicted the bacterial composition of the vaginal microbiota in an independent validation group. Since targeting of microRNAs is explored in the clinical setting, our results warrant investigation of whether microRNA modulation could be used for treating vaginosis recurrence and vaginosis-related diseases. Conversely, commensal bacteria could be used for treating diseases with microRNA aberrations.
阴道微生物群在阴道健康中起着至关重要的作用。许多育龄女性的阴道由其中一种微生物主导。然而,大量女性的阴道以多种其他厌氧菌的定殖为特征。值得注意的是,一些阴道微生物群未被主导的女性会患上细菌性阴道病,这与性传播感染和其他不良后果有关。然而,将阴道微生物群与宿主反应联系起来的相互作用和机制仍在研究中。有研究表明人类微小RNA与肠道微生物群之间存在联系,但对微小RNA与阴道微生物群相互作用的分析有限。在本研究中,我们对67名瑞典年轻女性的阴道样本进行了微小RNA表达阵列分析。根据阴道微生物群组成,微小RNA被聚类为不同的组。有趣的是,182种微小RNA在未被主导的群落中的表达显著升高,表明[某种微生物]与微小RNA之间存在拮抗关系。在表达升高的微小RNA中,10种微小RNA显示出优异的诊断潜力,通过受试者工作特征分析得以体现。我们在34个独立样本中进一步验证了我们的发现,其中顶级微小RNA候选物的表达在阴道微生物群中有力地将[某种微生物]主导的群落与未被主导的群落区分开来。值得注意的是,与未被主导的群落相比,[某种微生物]主导的群落显示出最显著的微小RNA差异表达。总之,我们证明了阴道微生物群与众多生殖器官微小RNA之间存在密切关系,这可能有助于在这个生物生态位中进行更深入的机制性相互作用。阴道微生物群与女性健康相关,其中未被主导的群落使女性更容易患疾病,包括人乳头瘤病毒(HPV)。然而,阴道微生物群与宿主之间的分子关系在很大程度上尚未被探索。在本研究中,我们调查了一组年轻女性中阴道微生物群与宿主微小RNA之间的联系。我们发现微小RNA的表达与阴道微生物群中[某种微生物]的丰度呈负相关。特别是,微小RNA miR-23a-3p和miR-130a-3p的表达在未被主导的群落中显著升高,在一个独立验证组中预测了阴道微生物群的细菌组成。由于在临床环境中对微小RNA的靶向作用正在被探索,我们的结果值得研究微小RNA调节是否可用于治疗阴道病复发和阴道病相关疾病。相反,共生细菌可用于治疗微小RNA异常的疾病。