Abstract：
Vaginal colonization by fungi may elicit genital inflammation and enhance the risk of adverse reproductive health outcomes, such as HIV acquisition. Cross-sectional studies have linked fungi with an absence of bacterial vaginosis (BV), but it is unclear whether shifts in vaginal bacteria alter the abundance of vaginal fungi. Vaginal swabs collected following topical metronidazole treatment for BV during the phase 2b, placebo-controlled trial of LACTIN-V, a Lactobacillus crispatus-based live biotherapeutic, were assayed with semi-quantitative PCR for the relative quantitation of fungi and key bacterial species and multiplex immunoassay for immune factors. Vaginal fungi increased immediately following metronidazole treatment for BV (adjusted P = 0.0006), with most of this increase attributable to Candida albicans. Vaginal fungi were independently linked to elevated levels of the proinflammatory cytokine interleukin (IL) 17A, although this association did not remain significant after correcting for multiple comparisons. Fungal relative abundance by semi-quantitative PCR returned to baseline levels within 1 month of metronidazole treatment and was not affected by LACTIN-V or placebo administration. Fungal abundance was positively associated with Lactobacillus species, negatively associated with BV-associated bacteria, and positively associated with a variety of proinflammatory cytokines and chemokines, including IL-17A, during and after study product administration. Antibiotic treatment for BV resulted in a transient expanded abundance of vaginal fungi in a subset of women which was unaffected by subsequent administration of LACTIN-V. Vaginal fungi were positively associated with Lactobacillus species and IL-17A and negatively associated with BV-associated bacteria; these associations were most pronounced in the longer-term outcomes.IMPORTANCEVaginal colonization by fungi can enhance the risk of adverse reproductive health outcomes and HIV acquisition, potentially by eliciting genital mucosal inflammation. We show that standard antibiotic treatment for bacterial vaginosis (BV) results in a transient increase in the absolute abundance of vaginal fungi, most of which was identified as Candida albicans. Vaginal fungi were positively associated with proinflammatory immune factors and negatively associated with BV-associated bacteria. These findings improve our understanding of how shifts in the bacterial composition of the vaginal microbiota may enhance proliferation by proinflammatory vaginal fungi, which may have important implications for risk of adverse reproductive health outcomes among women.
摘要：
真菌的阴道定植可能引起生殖器炎症，并增加不良生殖健康结果的风险。例如HIV感染。横断面研究将真菌与细菌性阴道病（BV）的缺失联系起来，但目前尚不清楚阴道细菌的变化是否会改变阴道真菌的丰度。在2b期局部甲硝唑治疗BV后收集阴道拭子，LACTIN-V的安慰剂对照试验，一种基于crispatus的活生物治疗，通过半定量PCR对真菌和关键细菌物种的相对定量以及免疫因子的多重免疫测定进行了分析。甲硝唑治疗BV后阴道真菌立即增加（调整后P=0.0006），这种增加大部分归因于白色念珠菌。阴道真菌与促炎细胞因子白细胞介素（IL）17A的水平升高独立相关，尽管在校正多重比较后,这种关联并不显著.通过半定量PCR的真菌相对丰度在甲硝唑治疗的1个月内恢复到基线水平，并且不受LACTIN-V或安慰剂给药的影响。真菌丰度与乳酸杆菌呈正相关，与BV相关细菌呈负相关，与多种促炎细胞因子和趋化因子呈正相关，包括IL-17A,在研究产品给药期间和之后。BV的抗生素治疗导致一部分女性阴道真菌的短暂增加，随后服用LACTIN-V不受影响。阴道真菌与乳酸杆菌和IL-17A呈正相关，与BV相关细菌呈负相关；这些关联在长期结局中最为明显。真菌的重要阴道定植可以增加不良生殖健康结果和艾滋病毒感染的风险，可能通过引发生殖器粘膜炎症。我们表明，细菌性阴道病（BV）的标准抗生素治疗会导致阴道真菌绝对丰度的短暂增加，其中大部分被鉴定为白色念珠菌。阴道真菌与促炎免疫因子呈正相关，与BV相关细菌呈负相关。这些发现提高了我们对阴道微生物群的细菌组成变化如何通过促炎阴道真菌增强增殖的理解。这可能对女性生殖健康不良结局的风险产生重要影响。
