Holm Johanna B, France Michael T, Gajer Pawel, Ma Bing, Brotman Rebecca M, Shardell Michelle, Forney Larry, Ravel Jacques
Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA.
Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.
bioRxiv. 2023 Mar 24:2023.03.24.533147. doi: 10.1101/2023.03.24.533147.
A 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.
MgCSTs 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 mgSs, as well as a mgSs of , were associated with a greater likelihood of Amsel bacterial vaginosis diagnosis. This 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.
MgCSTs 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.
占主导地位的阴道微生物群构成了抵御众多不良生殖道健康结局的第一道防线。然而，对于阴道微生物群调节保护作用的机制，人们的了解有限，因为先前的研究大多通过形态学评估和标记基因测序方法来描述其组成，而这些方法无法获取功能信息。为解决这一局限性，我们开发了宏基因组群落状态类型（mgCSTs），它利用宏基因组序列基于组成和功能来描述和定义阴道微生物群。
MgCSTs是根据分类学及其宏基因组中编码的功能潜力对微生物群进行分类的类别。MgCSTs反映了宏基因组亚种（mgSs）的独特组合，宏基因组亚种是微生物群中同一物种细菌菌株的集合。我们证明mgCSTs与年龄、种族等人口统计学特征以及阴道pH值和阴道涂片的革兰氏染色评估有关。重要的是，这些关联在由相同细菌物种主导的mgCSTs之间有所不同。一部分mgCSTs，包括由mgSs主导的六个中的三个，以及一个mgSs，与Amsel细菌性阴道病诊断的可能性增加有关。这个mgSs除了其他功能特征外，还编码了增强的上皮细胞附着遗传能力，这可能有助于细胞毒素介导的细胞裂解。最后，我们报告了一种mgSs和mgCST分类器，作为微生物群研究界易于应用的标准化方法。
MgCSTs是一种新颖且易于实施的方法，可在保持复杂宏基因组数据集功能独特性的同时降低其维度。MgCSTs能够研究同一物种的多种菌株及其功能多样性。未来对功能多样性的研究可能是揭示阴道微生物群调节对生殖道保护途径的关键。重要的是，我们的研究结果支持这样一种假设，即阴道微生物群之间的功能差异，包括那些在组成上可能相似的差异，是阴道健康的关键考虑因素。最终，mgCSTs可能会引发关于阴道微生物群在促进健康和疾病中的作用的新假设，并确定新的预后、诊断和治疗策略的靶点，以改善女性生殖健康。
