Metabolic signatures of bacterial vaginosis.
Metabolic signatures of bacterial vaginosis.
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DOI：
10.1128/mbio.00204-15
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发表时间：
2015-04-14
期刊：
影响因子：
6.4
通讯作者：
Fredricks DN
中科院分区：
文献类型：
--
作者：
Srinivasan S;Morgan MT;Fiedler TL;Djukovic D;Hoffman NG;Raftery D;Marrazzo JM;Fredricks DN
细菌性阴道病(BV)的特征是阴道微生物区系从以乳杆菌为主转变为以多种厌氧细菌为主的微生物区系。很少有研究将特定的代谢物与人类阴道中发现的细菌联系起来。在这里，我们报告了使用全球代谢组学方法与BV相关的代谢物成分和浓度的显著差异。我们使用来自第二组女性的样本和不同的平台来测量代谢物，进一步验证了重要的代谢物。在初步研究中，我们比较了40名患有BV的妇女和20名未患BV的妇女宫颈阴道灌洗液中的代谢物分布。用广谱聚合酶链式反应和焦磷酸测序检测阴道细菌的表达，用定量聚合酶链式反应检测细菌浓度。我们检测了279种指定的生物化学物质；患有BV的女性体内62%的代谢物水平有显著差异。无监督的代谢物聚集将患有和不患有BV的妇女区分开来。患有BV的女性的代谢物特征是氨基酸和二肽浓度较低，伴随着氨基酸分解代谢和多胺水平较高。在BV中，信号转导的二十烷类12-羟基二十碳四烯酸(12-HETE)水平较高，这是一种炎症的生物标志物。皱纹乳杆菌和简氏乳杆菌表现出相似的代谢物相关模式，这与BV相关细菌表现出的相关模式不同。几种代谢物与用于诊断BV的临床体征和症状(Amsel标准)显著相关，没有代谢物与所有四个临床标准相关。BV在多条代谢途径上有很强的代谢特征，这些特征与特定细菌的存在和浓度有关。细菌性阴道病(BV)是一种常见但高度神秘的疾病，与妇女及其新生儿的不良结局有关。阴道中的小分子代谢物可能影响宿主生理、影响微生物群落组成、影响不良健康结局的风险，但很少有研究全面研究BV的代谢组学特征。在这里，我们使用质谱仪将特定的代谢物与通过聚合酶链式反应在人体阴道中检测到的特定细菌联系起来。BV与影响氨基酸、碳水化合物和脂肪代谢的多个途径的强烈代谢信号有关，突出了BV的深刻代谢变化。这些特征与特定阴道细菌的存在和浓度有关，包括一些尚未培养的细菌，从而为许多代谢物的微生物来源提供了线索。这项研究的见解为开发新的BV诊断标记物和治疗或预防BV的新方法提供了机会。
Bacterial vaginosis (BV) is characterized by shifts in the vaginal microbiota from Lactobacillus dominant to a microbiota with diverse anaerobic bacteria. Few studies have linked specific metabolites with bacteria found in the human vagina. Here, we report dramatic differences in metabolite compositions and concentrations associated with BV using a global metabolomics approach. We further validated important metabolites using samples from a second cohort of women and a different platform to measure metabolites. In the primary study, we compared metabolite profiles in cervicovaginal lavage fluid from 40 women with BV and 20 women without BV. Vaginal bacterial representation was determined using broad-range PCR with pyrosequencing and concentrations of bacteria by quantitative PCR. We detected 279 named biochemicals; levels of 62% of metabolites were significantly different in women with BV. Unsupervised clustering of metabolites separated women with and without BV. Women with BV have metabolite profiles marked by lower concentrations of amino acids and dipeptides, concomitant with higher levels of amino acid catabolites and polyamines. Higher levels of the signaling eicosanoid 12-hydroxyeicosatetraenoic acid (12-HETE), a biomarker for inflammation, were noted in BV. Lactobacillus crispatus and Lactobacillus jensenii exhibited similar metabolite correlation patterns, which were distinct from correlation patterns exhibited by BV-associated bacteria. Several metabolites were significantly associated with clinical signs and symptoms (Amsel criteria) used to diagnose BV, and no metabolite was associated with all four clinical criteria. BV has strong metabolic signatures across multiple metabolic pathways, and these signatures are associated with the presence and concentrations of particular bacteria. Bacterial vaginosis (BV) is a common but highly enigmatic condition that is associated with adverse outcomes for women and their neonates. Small molecule metabolites in the vagina may influence host physiology, affect microbial community composition, and impact risk of adverse health outcomes, but few studies have comprehensively studied the metabolomics profile of BV. Here, we used mass spectrometry to link specific metabolites with particular bacteria detected in the human vagina by PCR. BV was associated with strong metabolic signatures across multiple pathways affecting amino acid, carbohydrate, and lipid metabolism, highlighting the profound metabolic changes in BV. These signatures were associated with the presence and concentrations of particular vaginal bacteria, including some bacteria yet to be cultivated, thereby providing clues as to the microbial origin of many metabolites. Insights from this study provide opportunities for developing new diagnostic markers of BV and novel approaches for treatment or prevention of BV.