Microbial supernatants from Mobiluncus mulieris, a bacteria strongly associated with spontaneous preterm birth, disrupts the cervical epithelial barrier through inflammatory and miRNA mediated mechanisms
Microbial supernatants from Mobiluncus mulieris, a bacteria strongly associated with spontaneous preterm birth, disrupts the cervical epithelial barrier through inflammatory and miRNA mediated mechanisms
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DOI：
10.1016/j.anaerobe.2019.102127
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发表时间：
2020-02-01
期刊：
影响因子：
2.3
通讯作者：
Anton, Lauren
中科院分区：
文献类型：
--
作者：
Dude, Carolynn M.;Saylany, Anissa;Anton, Lauren
最近的人类临床研究已经确定了子宫颈阴道（CV）空间中存在的一种严格厌氧的苛养细菌Mobiluncus mulieris与自发性早产（sPTB）密切相关。然而，这种关联的分子机制仍然未知。由于宫颈上皮屏障的破坏已被证明有助于sPTB之前的过早宫颈重塑，我们假设M。mulieris是一种与人类sPTB密切相关的微生物，具有改变宫颈上皮功能的能力。我们研究了M. mulieris能够通过体外模型系统中基于免疫学和表观遗传学的机制破坏宫颈上皮屏障。用培养的M. mulieris和上皮细胞通透性，免疫细胞因子和microRNAs（miRNAs）进行了研究。M. mulieris上清液显著增加细胞通透性和与宫颈上皮破裂相关的两种炎症介质IL-6和IL-8的表达。此外，用M. mulieris上清液还增加了与人的sPTB或较短妊娠长度相关的miRNA的表达。总的来说，这些结果表明M。mulieris诱导宫颈上皮屏障的分子和功能变化，被认为有助于sPTB的发病机制，这使我们能够假设靶向CV细菌如M. mulieris可以提供降低sPTB率的治疗机会。(C)2019爱思唯尔有限公司版权所有。
Recent human clinical studies have identified Mobiluncus mulieris, a fastidious strict anaerobic bacterium present in the cervicovaginal (CV) space, as being strongly associated with spontaneous preterm birth (sPTB). However, the molecular mechanisms that underlie this association remain unknown. As disruption of the cervical epithelial barrier has been shown to contribute to the premature cervical remodeling that precedes sPTB, we hypothesize that M. mulieris, a microbe strongly associated with sPTB in humans, has the ability to alter cervical epithelial function. We investigated if bacteria-free supernatants of M. mulieris were able to disrupt the cervical epithelial barrier through immunological and epigenetic based mechanisms in an in vitro model system. Ectocervical cells were treated with supernatant from cultured M. mulieris and epithelial cell permeability, immune cytokines and microRNAs (miRNAs) were investigated. M. mulieris supernatant significantly increased cell permeability and the expression of two inflammatory mediators associated with cervical epithelial breakdown, IL-6 and IL-8. Moreover, treatment of the ectocervical cells with the M. mulieris supernatant also increased the expression of miRNAs that have been associated with either sPTB or a shorter gestational length in humans. Collectively, these results suggest that M. mulieris induces molecular and functional changes in the cervical epithelial barrier thought to contribute to the pathogenesis of sPTB, which allows us to hypothesize that targeting CV bacteria such as M. mulieris could provide a therapeutic opportunity to reduce sPTB rates. (C) 2019 Elsevier Ltd. All rights reserved.