Integrating compositional and functional content to describe vaginal microbiomes in health and disease.
Integrating compositional and functional content to describe vaginal microbiomes in health and disease.
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DOI：
10.1186/s40168-023-01692-x
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发表时间：
2023-11-30
期刊：
影响因子：
15.5
通讯作者：
中科院分区：
文献类型：
--
作者：
乳杆菌主导的阴道微生物群提供了抵御不良生殖道健康后果的第一道防线。然而，对阴道微生物群调节保护的机制了解有限，因为以前的工作大多通过形态评估和标记基因测序方法描述其组成，而不能捕捉功能信息。为了解决这一差距，我们开发了元基因组群落状态类型(MgCSTs)，它使用元基因组序列来描述和定义基于组成和功能潜力的阴道微生物群。MGCST是根据分类和编码在其元基因组中的功能潜力分类的微生物群的类别。Mgcst反映了在微生物组中的元组亚种(Mgs)的独特组合，即同一物种的细菌菌株的组合。我们证明mgCST与年龄、种族以及阴道涂片的阴道pH值和革兰氏染色评估等人口统计学因素有关。重要的是，这些关联在由相同细菌种类主导的mgCST之间有所不同。根据Amsel临床诊断标准，MgCST的一个子集，包括以阴道加德纳菌MGSS为主的6个MgS中的3个，以及L.iners的MGS，与细菌性阴道病的可能性更大相关。除了其他功能特征外，这种细菌还编码了增强的上皮细胞附着的遗传能力，这可能有助于细胞毒素介导的细胞裂解。最后，我们报告了一个mgSS和mgCST分类器，它提供了源代码，可以被微生物组研究社区改编使用。它是一种新的、易于实现的方法，可以在保持功能唯一性的同时降低复杂元基因组数据集的维度。利用该技术可以对同一物种的多个菌株以及该物种的功能多样性进行研究。未来对功能多样性的研究可能是解开阴道微生物群调节生殖道保护的途径的关键。重要的是，我们的发现支持这样一种假设，即阴道微生物群之间的功能差异，包括那些看起来可能成分相似的微生物群，是阴道健康的关键考虑因素。最终，mgCSTs可能导致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，以改善妇女的生殖健康。视频摘要在线版本包含可在10.1186/s40168023-01692-x上查阅的补充材料。
A Lactobacillus-dominated vaginal microbiome provides the first line of defense against 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 gap, we developed metagenomic community state types (mgCSTs) which use metagenomic sequences to describe and define vaginal microbiomes based on both composition and functional potential. 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 Gardnerella vaginalis mgSs, as well as mgSs of L. iners, were associated with a greater likelihood of bacterial vaginosis diagnosed by Amsel clinical criteria. 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 for which source code is provided and may be adapted for use by the microbiome research community. MgCSTs are a novel and easily implemented approach to reduce the dimension of complex metagenomic datasets while maintaining their functional uniqueness. MgCSTs enable the 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 the protection of 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. Video Abstract The online version contains supplementary material available at 10.1186/s40168-023-01692-x.
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影响因子：
9.2
作者：
Feehily C;Crosby D;Walsh CJ;Lawton EM;Higgins S;McAuliffe FM;Cotter PD
通讯作者：
Cotter PD
影响因子：
17.1
作者：
Gajer P;Brotman RM;Bai G;Sakamoto J;Schütte UM;Zhong X;Koenig SS;Fu L;Ma ZS;Zhou X;Abdo Z;Forney LJ;Ravel J
通讯作者：
Ravel J
影响因子：
3.9
作者：
Amabebe E;Anumba DOC
通讯作者：
Anumba DOC
影响因子：
1.8
作者：
Hennig, Christian
通讯作者：
Hennig, Christian
影响因子：
3.7
作者：
Bilardi, Jade E.;Walker, Sandra;Bradshaw, Catriona
通讯作者：
Bradshaw, Catriona