Department of Obstetrics and Gynecology, College of Medicine-Phoenix, University of Arizona, Phoenix, AZ, United States.
Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom.
Front Cell Infect Microbiol. 2021 Dec 23;11:759697. doi: 10.3389/fcimb.2021.759697. eCollection 2021.
The cervicovaginal microbiome plays an important role in protecting women from dysbiosis and infection caused by pathogenic microorganisms. In healthy reproductive-age women the cervicovaginal microbiome is predominantly colonized by protective spp. The loss of these protective bacteria leads to colonization of the cervicovaginal microenvironment by pathogenic microorganisms resulting in dysbiosis and bacterial vaginosis (BV). and sp. are two of the many anaerobes that can contribute to BV, a condition associated with multiple adverse obstetric and gynecological outcomes. has been linked to high Nugent scores (relating to BV morphotypes) and preterm birth (PTB), whilst some bacterial members of the family are highly prevalent in BV, and identified in ~85-95% of cases. The functional impact of and sp. in BV is still poorly understood. To determine the individual immunometabolic contributions of sp. and within the cervicovaginal microenvironment, we utilized our well-characterized human three-dimensional (3-D) cervical epithelial cell model in combination with multiplex immunoassays and global untargeted metabolomics approaches to identify key immune mediators and metabolites related to and sp. infections. We found that infection with significantly elevated multiple proinflammatory markers (IL-6, IL-8, TNF-α and MCP-1) and altered metabolites related to energy metabolism (nicotinamide and succinate) and oxidative stress (cysteinylglycine, cysteinylglycine disulfide and 2-hydroxygluatrate). sp. infection significantly elevated multiple sphingolipids and glycerolipids related to epithelial barrier function, and biogenic amines (putrescine and cadaverine) associated with elevated vaginal pH, vaginal amine odor and vaginal discharge. Our study elucidated that elevated multiple proinflammatory markers relating to PTB and STI acquisition, as well as altered energy metabolism and oxidative stress, whilst sp. upregulated multiple biogenic amines associated with the clinical diagnostic criteria of BV. Future studies are needed to evaluate how these bacteria interact with other BV-associated bacteria within the cervicovaginal microenvironment.
阴道宫颈微生物组在保护女性免受由病原微生物引起的生态失调和感染方面起着重要作用。在健康育龄期女性中，阴道宫颈微生物组主要被保护性 spp 定植。这些保护性细菌的丧失导致阴道宫颈微环境被病原微生物定植，导致生态失调和细菌性阴道病 (BV)。 和 sp. 是许多可导致 BV 的厌氧菌中的两种，BV 与多种不良产科和妇科结局相关。 已与高 Nugent 评分（与 BV 形态有关）和早产 (PTB) 相关，而 BV 中高度流行的一些细菌成员属于 家族，在约 85-95%的病例中被识别。 和 sp. 在 BV 中的功能影响仍知之甚少。为了确定 sp. 和 在阴道宫颈微环境中的个体免疫代谢贡献，我们利用我们经过充分表征的人三维 (3-D) 宫颈上皮细胞模型，结合多重免疫分析和全局非靶向代谢组学方法，鉴定与 和 sp. 感染相关的关键免疫介质和代谢物。我们发现， 感染显着上调了多种促炎标志物（IL-6、IL-8、TNF-α 和 MCP-1）和与能量代谢（烟酰胺和琥珀酸）和氧化应激（半胱氨酸甘氨酸、半胱氨酸甘氨酸二硫化物和 2-羟基谷氨酸）相关的代谢物。 sp. 感染显着上调了与上皮屏障功能相关的多种鞘脂和甘油脂，以及与阴道 pH 值升高、阴道胺气味和阴道分泌物相关的生物胺（腐胺和尸胺）。我们的研究表明， 上调了与 PTB 和 STI 获得相关的多种促炎标志物，以及改变的能量代谢和氧化应激，而 sp. 上调了与 BV 临床诊断标准相关的多种生物胺。需要进一步的研究来评估这些细菌如何与阴道宫颈微环境中的其他与 BV 相关的细菌相互作用。
