BACKGROUND Recent studies suggest that alterations in the vaginal microbiome allow for the assessment of the risk for spontaneous preterm birth (PTB), the leading cause of neonatal morbidity and mortality worldwide. However, the associations between the local immune response and the vaginal microbiome are still poorly understood. Herein, we characterize the vaginal host immune-microbiome interactions in women who ultimately underwent PTB and in those who delivered at term. METHODS Vaginal fluid samples from 52 pregnant women (of whom 18 underwent PTB and 34 delivered at term) were collected between 10 and 32 weeks of gestation in a case-control study. Concentrations of 33 immune mediators were determined using sensitive and specific immunoassays. The previously published 16S rRNA gene sequence and bacterial phylotype data of these subjects were utilized in this study. Linear mixed effects models were utilized to test associations between vaginal immune mediator concentrations and bacterial phylotype relative abundances. RESULTS 1) In the overall study population, vaginal concentrations of CXCL10, CCL2, CCL3, SLP1 and VEGF negatively correlated with non-Lactobacillus, Community State Type IV (CST IV) members of the vaginal microbiome; 2) CXCL10, in particular, negatively correlated with 15 bacterial phylotypes, most of which are typical members of CST IV, such as Gardnerella vaginalis, Megasphaera spp., and Atopobium vaginae; 3) Gemella spp., also members of CST IV, negatively correlated with vaginal concentrations of VEGF, CCL2, CCL3, SLPI, and CXCL10; 4) when comparing PTB cases to term controls, five soluble immune mediators (CCL26, CCL22, CCL2, CXCL10, and IL-16), especially CCL26, were negatively correlated with five typical members of CST IV: Sneathia sanguinegens, Parvimonas micra, Veillonellaceae, BVAB2, and Gemella spp.; and 5) Sneathia sanguinegens had stronger negative associations with all five soluble immune mediators (CCL26, CCL22, CCL2, CXCL10, and IL-16) in PTB cases than in term controls. CONCLUSIONS The assessment of vaginal host immune-microbiome interactions revealed that specific soluble immune mediators, mainly CXCL10, negatively correlated with typical members of CST IV of the vaginal microbiome. Sneathia sanguinegens, in particular, had stronger negative associations with different immune mediators, including CXCL10 and CCL26, in women who ultimately underwent PTB compared to those who delivered at term. These findings provide insight into the vaginal host immune-microbiome interactions in normal and complicated pregnancies.

中文翻译：

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最终经历自发性早产或足月分娩的主要是非洲裔美国妇女的阴道宿主免疫微生物组相互作用

背景 最近的研究表明，阴道微生物组的改变可以评估自发性早产 (PTB) 的风险，PTB 是全球新生儿发病率和死亡率的主要原因。然而，局部免疫反应与阴道微生物组之间的关联仍知之甚少。在此，我们描述了最终接受 PTB 的女性和足月分娩的女性阴道宿主免疫-微生物组的相互作用。方法 在病例对照研究中收集了 52 名孕妇（其中 18 名接受 PTB 和 34 名足月分娩）的阴道液样本，这些样本在妊娠 10 至 32 周之间进行。使用灵敏和特异的免疫测定法测定了 33 种免疫介质的浓度。本研究利用了先前公布的这些受试者的 16S rRNA 基因序列和细菌系统发育数据。线性混合效应模型用于测试阴道免疫介质浓度与细菌系统发育相对丰度之间的关联。结果 1) 在整个研究人群中，CXCL10、CCL2、CCL3、SLP1 和 VEGF 的阴道浓度与阴道微生物群的非乳酸杆菌、社区状态 IV (CST IV) 成员呈负相关；2）CXCL10，尤其是与15种细菌系统发育型呈负相关，其中大部分是CST IV的典型成员，如Gardnerella vaginis、Megasphaera spp.和Atopobium v​​aginae；3) Gemella spp.，也是 CST IV 的成员，与 VEGF、CCL2、CCL3、SLPI 和 CXCL10 的阴道浓度呈负相关；4）当将 PTB 病例与足月对照进行比较时，五种可溶性免疫介质（CCL26、CCL22、CCL2、CXCL10 和 IL-16），尤其是 CCL26，与 CST IV 的五个典型成员呈负相关：Sneathia sanguinegens、Parvimonas micra、Veillonellaceae 、BVAB2 和 Gemella 属；和 5) 与足月对照相比，PTB 病例中的 Sneathia sanguinegens 与所有五种可溶性免疫介质（CCL26、CCL22、CCL2、CXCL10 和 IL-16）的负相关性更强。结论阴道宿主免疫-微生物组相互作用的评估表明，特定的可溶性免疫介质，主要是 CXCL10，与阴道微生物组 CST IV 的典型成员呈负相关。特别是 Sneathia sanguinegens，与不同的免疫介质，包括 CXCL10 和 CCL26，有更强的负相关，与足月分娩的女性相比，最终接受 PTB 的女性。这些发现提供了对正常和复杂妊娠中阴道宿主免疫-微生物组相互作用的深入了解。