Association between statin use, the vaginal microbiome, and Gardnerella vaginalis vaginolysin-mediated cytotoxicity.
Association between statin use, the vaginal microbiome, and Gardnerella vaginalis vaginolysin-mediated cytotoxicity.
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他汀类药物的使用，阴道微生物组和阴道阴道阴道蛋白介导的细胞毒性之间的关联。
DOI：
10.1371/journal.pone.0183765
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Jefferson KK
中科院分区：
文献类型：
--
作者：
Abdelmaksoud AA;Girerd PH;Garcia EM;Brooks JP;Leftwich LM;Sheth NU;Bradley SP;Serrano MG;Fettweis JM;Huang B;Strauss JF 3rd;Buck GA;Jefferson KK
细菌性阴道病（BV）是阴道微生物组的主要生态失调。导致BV发展的途径还不清楚。阴道加德纳菌经常与BV相关。G.迷走神经炎产生胆固醇依赖性溶细胞素（CDC），即阴道溶素，其可裂解多种人类细胞，并被认为在发病机制中起作用。由于阴道溶素发挥作用需要膜胆固醇，并且由于HMG-CoA还原酶抑制剂（他汀类药物）不仅影响血清胆固醇水平，还影响膜水平，因此我们假设他汀类药物可能会影响阴道微生物组。为了研究他汀类药物的使用与阴道微生物组之间的关系，我们分析了对133名参与阴道人类微生物组项目并在采样时服用他汀类药物的女性，152名报告高胆固醇水平但未服用他汀类药物的女性以及316名未报告高胆固醇的女性的阴道样本进行的16 S rRNA基因分类调查。为了检查他汀类药物对阴道溶素（阴道加德纳菌产生的胆固醇依赖性溶细胞素（CDC））的细胞溶解作用的影响，我们评估了VK 2 E6/E7阴道上皮细胞的辛伐他汀预处理对阴道溶素介导的细胞毒性的影响。G.服用他汀类药物的女性的迷走神经功能显著低于未服用他汀类药物的女性。使用他汀类药物的女性相对于胆固醇水平正常的女性具有较高的卷曲乳杆菌平均比例，并且相对于胆固醇高但未服用他汀类药物的女性具有较高的詹氏乳杆菌水平。在体外实验中，辛伐他汀预处理的阴道上皮细胞对阴道溶素具有相对抵抗力，这种作用可被胆固醇抑制。在这项横断面研究中，他汀类药物的使用与G。阴道微生物组中有益乳酸杆菌的比例更大。他汀类药物的使用与G.阴道炎可能与阴道溶素功能的抑制有关。
Bacterial vaginosis (BV) is the leading dysbiosis of the vaginal microbiome. The pathways leading towards the development of BV are not well understood. Gardnerella vaginalis is frequently associated with BV. G. vaginalis produces the cholesterol-dependent cytolysin (CDC), vaginolysin, which can lyse a variety of human cells and is thought to play a role in pathogenesis. Because membrane cholesterol is required for vaginolysin to function, and because HMG-CoA reductase inhibitors (statins) affect not only serum levels of cholesterol but membrane levels as well, we hypothesized that statins might affect the vaginal microbiome. To investigate the relationship between use of the statins and the vaginal microbiome, we analyzed 16S rRNA gene taxonomic surveys performed on vaginal samples from 133 women who participated in the Vaginal Human Microbiome Project and who were taking statins at the time of sampling, 152 women who reported high cholesterol levels but were not taking statins, and 316 women who did not report high cholesterol. To examine the effect of statins on the cytolytic effect of vaginolysin, the cholesterol-dependent cytolysin (CDC) produced by Gardnerella vaginalis, we assessed the effect of simvastatin pretreatment of VK2E6/E7 vaginal epithelial cells on vaginolysin-mediated cytotoxicity. The mean proportion of G. vaginalis among women taking statins was significantly lower relative to women not using statins. Women using statins had higher mean proportions of Lactobacillus crispatus relative to women with normal cholesterol levels, and higher levels of Lactobacillus jensenii relative to women with high cholesterol but not taking statins. In vitro, vaginal epithelial cells pretreated with simvastatin were relatively resistant to vaginolysin and this effect was inhibited by cholesterol. In this cross-sectional study, statin use was associated with reduced proportions of G. vaginalis and greater proportions of beneficial lactobacilli within the vaginal microbiome. The negative association between statin use and G. vaginalis may be related to inhibition of vaginolysin function.
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DOI：
10.1097/01.qai.0000146599.47925.e0
发表时间：
2005-07-01
影响因子：
3.6
作者：
Cohn, JA;Hashemi, FB;Spear, GT
通讯作者：
Spear, GT
影响因子：
2.8
作者：
Fettweis, Jennifer M.;Brooks, J. Paul;Buck, Gregory A.
通讯作者：
Buck, Gregory A.
影响因子：
2.6
作者：
Hotomi, Muneki;Yuasa, Jun;Yamanaka, Noboru
通讯作者：
Yamanaka, Noboru
影响因子：
9.8
作者：
Klebanoff, MA;Hillier, SL;Langer, O
通讯作者：
Langer, O
影响因子：
2.9
作者：
Koter, M;Broncel, M;Franiak, I
通讯作者：
Franiak, I