Common Cervicovaginal Microbial Supernatants Alter Cervical Epithelial Function: Mechanisms by Which Lactobacillus crispatus Contributes to Cervical Health.
Common Cervicovaginal Microbial Supernatants Alter Cervical Epithelial Function: Mechanisms by Which Lactobacillus crispatus Contributes to Cervical Health.
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DOI：
10.3389/fmicb.2018.02181
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发表时间：
2018
影响因子：
5.2
通讯作者：
Elovitz MA
中科院分区：
文献类型：
--
作者：
Anton L;Sierra LJ;DeVine A;Barila G;Heiser L;Brown AG;Elovitz MA
宫颈阴道（CV）微生物群与非妊娠女性的阴道健康和疾病相关。最近在孕妇中的研究表明，特定的CV微生物与早产（PTB）有关。虽然CV微生物群与不良结局之间的关联已得到证实，但调节该关联的机制仍不清楚。由于CV空间包含上皮屏障，我们假设CV微生物群可以改变上皮屏障功能。我们研究了卷曲乳杆菌、惰性乳杆菌和阴道加德纳氏菌对宫颈上皮屏障功能的生物学、分子和表观遗传学影响，并确定L。crispatus减轻脂多糖（LPS）和G.宫颈上皮屏障上的迷走神经作为CV微生物群减轻疾病风险的可能机制。用L. crispatus，L. iners，和G.使用单独或组合的无迷走神经炎细菌的上清液来测量细胞通透性、粘附连接蛋白、炎性介质和miRNA。L. iners和G.迷走神经暴露可溶性上皮钙粘蛋白在暴露于L. iners而不是G.迷走草属卷曲的一个Luminex细胞因子/趋化因子小组显示，在所有三个无菌上清液中，L。iners和G.具有多种炎症作用的迷走神经炎。L. iners和G.迷走神经损伤改变了宫颈、微生物和炎症相关的miRNAs的表达。L. crispatus减轻LPS或G.阴道炎引起的宫颈上皮屏障破坏，并逆转G.阴道炎介导的miRNA表达增加。G.妊娠C57/B6小鼠CV空间的迷走神经定殖导致100%PTB。这些结果表明L. iners和G.阴道炎通过调节粘附连接蛋白、宫颈免疫应答和miRNA表达改变宫颈上皮屏障。这些结果为L. crispatus通过减轻LPS或G.阴道炎诱导的miRNA与宫颈重塑、炎症和PTB相关。这项研究提供了进一步的证据，表明CV微生物群通过改变宫颈上皮屏障和启动PTB在宫颈功能中发挥作用。因此，靶向CV微生物群和/或其对宫颈上皮的影响可能是预防PTB的潜在治疗策略。
Cervicovaginal (CV) microbiota is associated with vaginal health and disease in non-pregnant women. Recent studies in pregnant women suggest that specific CV microbes are associated with preterm birth (PTB). While the associations between CV microbiota and adverse outcomes have been demonstrated, the mechanisms regulating the associations remain unclear. As the CV space contains an epithelial barrier, we postulate that CV microbiota can alter the epithelial barrier function. We investigated the biological, molecular, and epigenetic effects of Lactobacillus crispatus, Lactobacillus iners, and Gardnerella vaginalis on the cervical epithelial barrier function and determined whether L. crispatus mitigates the effects of lipopolysaccharide (LPS) and G. vaginalis on the cervical epithelial barrier as a possible mechanism by which CV microbiota mitigates disease risk. Ectocervical and endocervical cells treated with L. crispatus, L. iners, and G. vaginalis bacteria-free supernatants alone or combined were used to measure cell permeability, adherens junction proteins, inflammatory mediators, and miRNAs. Ectocervical and endocervical permeability increased after L. iners and G. vaginalis exposure. Soluble epithelial cadherin increased after exposure to L. iners but not G. vaginalis or L. crispatus. A Luminex cytokine/chemokine panel revealed increased proinflammatory mediators in all three bacteria-free supernatants with L. iners and G. vaginalis having more diverse inflammatory effects. L. iners and G. vaginalis altered the expression of cervical-, microbial-, and inflammatory-associated miRNAs. L. crispatus mitigated the LPS or G. vaginalis-induced disruption of the cervical epithelial barrier and reversed the G. vaginalis-mediated increase in miRNA expression. G. vaginalis colonization of the CV space of a pregnant C57/B6 mouse resulted in 100% PTB. These findings demonstrate that L. iners and G. vaginalis alter the cervical epithelial barrier by regulating adherens junction proteins, cervical immune responses, and miRNA expressions. These results provide evidence that L. crispatus confers protection to the cervical epithelial barrier by mitigating LPS- or G. vaginalis-induced miRNAs associated with cervical remodeling, inflammation, and PTB. This study provides further evidence that the CV microbiota plays a role in cervical function by altering the cervical epithelial barrier and initiating PTB. Thus, targeting the CV microbiota and/or its effects on the cervical epithelium may be a potential therapeutic strategy to prevent PTB.
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新型的阴道菌群定殖模型为杀生作用机理提供了新的见解。
影响因子：
6.4
作者：
Fichorova RN;Yamamoto HS;Delaney ML;Onderdonk AB;Doncel GF
通讯作者：
Doncel GF
影响因子：
3.7
作者：
Dols JA;Molenaar D;van der Helm JJ;Caspers MP;de Kat Angelino-Bart A;Schuren FH;Speksnijder AG;Westerhoff HV;Richardus JH;Boon ME;Reid G;de Vries HJ;Kort R
通讯作者：
Kort R
早产的妇女具有独特的宫颈阴道代谢组。
影响因子：
9.8
作者：
Ghartey J;Bastek JA;Brown AG;Anglim L;Elovitz MA
通讯作者：
Elovitz MA
DOI：
10.1016/s0002-9378(96)70395-2
发表时间：
1996-01-01
影响因子：
9.8
作者：
Cox, SM;Bohman, VR;Leveno, KJ
通讯作者：
Leveno, KJ
DOI：
10.1073/pnas.1502875112
发表时间：
2015-09-01
影响因子：
11.1
作者：
DiGiulio, Daniel B.;Callahan, Benjamin J.;Relman, David A.
通讯作者：
Relman, David A.