Background

Bacterial vaginosis—a condition defined by a shift from Lactobacillus dominance to a polymicrobial, anaerobic bacterial community—increases the risk of acquiring sexually transmitted infections and other complications of the female reproductive tract. Antibiotic treatment frequently fails to return the microbiome to an optimal Lactobacillus-dominated state. No criteria currently exist to identify the patients likely to experience treatment failure.

Objective

We sought to identify the pretreatment community signatures associated with treatment failure through 16S ribosomal RNA gene analysis.

Study Design

Twenty-eight women who were enrolled in an oral metronidazole treatment trial of bacterial vaginosis were studied. Cervicovaginal lavage samples were collected before metronidazole treatment and at 7 and 30 days posttreatment. Cervicovaginal lavage DNA was amplified and sequenced using a paired-end, V4 region 2×150 MiSeq run.

Results

Of the 28 women, 25% failed to clear bacterial vaginosis; 35.7% demonstrated a transient clearance, shifting to community-type 2 (Lactobacillus iners dominant) at visit 2 only; 7.1% demonstrated a delayed clearance, reaching community-type 2 at the final visit only; and 32.1% of patients experienced sustained bacterial vaginosis clearance. Examination of the community composition and structure demonstrated that both the richness and the evenness were significantly lower for the women who experienced sustained clearance, whereas the women who failed to clear bacterial vaginosis possessed the highest median levels of richness, evenness, and diversity pretreatment. Soluble immune factors in the lower reproductive tract improved significantly following a shift from community-type 4 to a Lactobacillus-dominant microbiome, with the samples categorized as community-type 2 possessing significantly higher levels of secretory leukocyte protease inhibitor, growth-regulated alpha protein, and macrophage inflammatory protein-3 and significantly lower levels of intercellular adhesion molecule-1. Although the shifts to Lactobacillus dominance improved the markers of mucosal tissue health, these gains were only temporary among the women who experienced recurrence.

Conclusion

Assemblies of highly diverse microbiota are associated with the enhanced resilience of bacterial vaginosis to standard metronidazole treatment. These communities may be foundational to treatment resistance or simply an indication of a well-established community made possible by canonical biofilm-forming taxa. Future studies must target the transcriptional activity of these communities under the pressure of antibiotic treatment to resolve the mechanisms of their resistance.

中文翻译：

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甲硝唑治疗后复发性细菌性阴道病与诊断时微生物群丰富度相关

 背景

细菌性阴道病是一种由乳杆菌占主导地位转变为多种微生物、厌氧细菌群落的疾病，会增加获得性传播感染和女性生殖道其他并发症的风险。抗生素治疗经常无法使微生物组恢复到以乳酸菌为主的最佳状态。目前尚无标准来识别可能经历治疗失败的患者。

 客观的

我们试图通过 16S 核糖体 RNA 基因分析来识别与治疗失败相关的治疗前群落特征。

 研究设计

对参加口服甲硝唑治疗细菌性阴道病试验的 28 名女性进行了研究。在甲硝唑治疗前以及治疗后 7 天和 30 天收集宫颈阴道灌洗样本。使用双端 V4 区域 2×150 MiSeq 运行对宫颈阴道灌洗液 DNA 进行扩增和测序。

 结果

在28名女性中，25%未能清除细菌性阴道病； 35.7% 的患者表现出短暂清除，仅在第 2 次访视时转变为群落类型 2（惰性乳杆菌占优势）； 7.1% 表现出延迟清除，仅在最后一次就诊时达到社区类型 2； 32.1%的患者经历了持续的细菌性阴道病清除。对群落组成和结构的检查表明，经历持续清除的女性的丰富度和均匀度均显着较低，而未能清除细菌性阴道病的女性在预处理中拥有最高的丰富度、均匀度和多样性中位水平。从群落 4 型微生物群转变为乳杆菌占主导地位的微生物群后，下生殖道中的可溶性免疫因子显着改善，群落 2 型样本的分泌性白细胞蛋白酶抑制剂、生长调节 α 蛋白、和巨噬细胞炎症蛋白-3，并显着降低细胞间粘附分子-1的水平。尽管乳酸菌优势的转变改善了粘膜组织健康的标志物，但这些收益对于经历复发的女性来说只是暂时的。

 结论

高度多样化的微生物群与细菌性阴道病对标准甲硝唑治疗的抵抗力增强有关。这些群落可能是治疗耐药性的基础，或者只是通过典型的生物膜形成类群而形成的完善群落的指示。未来的研究必须针对这些群落在抗生素治疗压力下的转录活性，以解决其耐药机制。