Abdelmaksoud Abdallah A, Girerd Philippe H, Garcia Erin M, Brooks J Paul, Leftwich Lauren M, Sheth Nihar U, Bradley Steven P, Serrano Myrna G, Fettweis Jennifer M, Huang Bernice, Strauss Jerome F, Buck Gregory A, Jefferson Kimberly K
Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, Virginia, United States of America.
Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, Virginia, United States of America.
PLoS One. 2017 Aug 28;12(8):e0183765. doi: 10.1371/journal.pone.0183765. eCollection 2017.
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.
细菌性阴道病（BV）是阴道微生物群失调的主要原因。导致BV发生的途径尚不完全清楚。阴道加德纳菌常与BV相关。阴道加德纳菌产生胆固醇依赖性细胞溶素（CDC）——阴道溶素，它能溶解多种人类细胞，并被认为在发病机制中起作用。由于阴道溶素发挥功能需要膜胆固醇，且3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂（他汀类药物）不仅会影响血清胆固醇水平，还会影响膜胆固醇水平，我们推测他汀类药物可能会影响阴道微生物群。
为了研究他汀类药物的使用与阴道微生物群之间的关系，我们分析了对133名参与阴道人类微生物群项目且在采样时正在服用他汀类药物的女性、152名报告胆固醇水平高但未服用他汀类药物的女性以及316名未报告胆固醇水平高的女性的阴道样本进行的16S rRNA基因分类调查。为了研究他汀类药物对阴道加德纳菌产生的胆固醇依赖性细胞溶素（CDC）——阴道溶素的细胞溶解作用的影响，我们评估了辛伐他汀预处理VK2E6/E7阴道上皮细胞对阴道溶素介导的细胞毒性的影响。
服用他汀类药物的女性中阴道加德纳菌的平均比例相对于未使用他汀类药物的女性显著降低。与胆固醇水平正常的女性相比，使用他汀类药物的女性中卷曲乳杆菌的平均比例更高，与胆固醇水平高但未服用他汀类药物的女性相比，詹氏乳杆菌的水平更高。在体外，用辛伐他汀预处理的阴道上皮细胞对阴道溶素相对耐药，且这种作用被胆固醇抑制。
在这项横断面研究中，使用他汀类药物与阴道微生物群中阴道加德纳菌比例降低和有益乳杆菌比例增加有关。他汀类药物的使用与阴道加德纳菌之间的负相关可能与抑制阴道溶素功能有关。
