High-resolution functional description of vaginal microbiomes in health and disease.
High-resolution functional description of vaginal microbiomes in health and disease.
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阴道微生物组在健康和疾病中的高分辨率功能描述。
DOI：
10.1101/2023.03.24.533147
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Ravel,Jacques
中科院分区：
文献类型：
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作者：
Holm,JohannaB;France,MichaelT;Gajer,Pawel;Ma,Bing;Brotman,RebeccaM;Shardell,Michelle;Forney,Larry;Ravel,Jacques
背景以乳酸杆菌为主的阴道微生物组提供了对抗许多不良生殖道健康结果的第一道防线。然而，对阴道微生物组调节保护的机制的理解有限，因为先前的工作主要通过形态评估和标记基因测序方法描述其组成，这些方法不能捕获功能信息。为了解决这个问题，我们开发了宏基因组社区状态类型（mgCSTs），它使用宏基因组序列来描述和定义阴道微生物组的基础上的组成和functions.ResultsMgCSTs是分类使用分类和功能潜力编码在他们的宏基因组的微生物组的类别。MgCST反映了宏基因组亚种（MgS）的独特组合，其是微生物组内相同物种的细菌菌株的集合。我们证明，mgCST与人口统计学，如年龄和种族，以及阴道pH值和阴道涂片革兰氏染色评估。重要的是，这些关联在由相同细菌物种主导的mgCST之间变化。mgCST的一个子集，包括加德纳菌属占优势的六种mgSs中的三种，以及L.与Amsel细菌性阴道病诊断的可能性更大相关。这个L。iners mgSs，在其他功能特征中，编码增强的上皮细胞附着的遗传能力，这可以促进细胞毒素介导的细胞裂解。最后，我们报告了一个mgSs和mgCST分类器作为一个易于应用的，标准化的方法，用于由微生物组research community. ConclusionsMgCST是一种新颖的，易于实现的方法，以减少复杂的宏基因组数据集的维数，同时保持其功能的独特性。MgCST使得能够研究相同物种的多个菌株以及该物种中的功能多样性。未来对功能多样性的研究可能是解开阴道微生物组调节生殖道保护的途径的关键。重要的是，我们的研究结果支持了这样一种假设，即阴道微生物组之间的功能差异，包括那些可能看起来成分相似的微生物组，是阴道健康的关键因素。最终，mgCST可能会导致关于阴道微生物组在促进健康和疾病中的作用的新假设，并确定新的预后，诊断和治疗策略的目标，以改善女性的生殖器健康。
BackgroundA Lactobacillus-dominated vaginal microbiome provides the first line of defense against numerous adverse genital tract health outcomes. However, there is limited understanding of the mechanisms by which the vaginal microbiome modulates protection, as prior work mostly described its composition through morphologic assessment and marker gene sequencing methods that do not capture functional information. To address this limitation, we developed metagenomic community state types (mgCSTs) which uses metagenomic sequences to describe and define vaginal microbiomes based on both composition and function.ResultsMgCSTs are categories of microbiomes classified using taxonomy and the functional potential encoded in their metagenomes. MgCSTs reflect unique combinations of metagenomic subspecies (mgSs), which are assemblages of bacterial strains of the same species, within a microbiome. We demonstrate that mgCSTs are associated with demographics such as age and race, as well as vaginal pH and Gram stain assessment of vaginal smears. Importantly, these associations varied between mgCSTs predominated by the same bacterial species. A subset of mgCSTs, including three of the six predominated by Gardnerella mgSs, as well as a mgSs of L. iners, were associated with a greater likelihood of Amsel bacterial vaginosis diagnosis. This L. iners mgSs, among other functional features, encoded enhanced genetic capabilities for epithelial cell attachment that could facilitate cytotoxin-mediated cell lysis. Finally, we report a mgSs and mgCST classifier as an easily applied, standardized method for use by the microbiome research community.ConclusionsMgCSTs are a novel and easily implemented approach to reducing the dimension of complex metagenomic datasets, while maintaining their functional uniqueness. MgCSTs enable investigation of multiple strains of the same species and the functional diversity in that species. Future investigations of functional diversity may be key to unraveling the pathways by which the vaginal microbiome modulates protection to the genital tract. Importantly, our findings support the hypothesis that functional differences between vaginal microbiomes, including those that may look compositionally similar, are critical considerations in vaginal health. Ultimately, mgCSTs may lead to novel hypotheses concerning the role of the vaginal microbiome in promoting health and disease, and identify targets for novel prognostic, diagnostic, and therapeutic strategies to improve women’s genital health.