Liang Yijia, Zhao Changying, Wen Yan, Sheng Dashuang, Wei Tiantian, Hu Tianqi, Dai Junhui, Zhao Guoping, Yang Sijie, Wang Qinghua, Zhang Lei
Microbiome-X, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, China.
Reproductive Medicine Center, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, China.
Front Immunol. 2024 Nov 18;15:1481611. doi: 10.3389/fimmu.2024.1481611. eCollection 2024.
This study aimed to identify immune states associated with a high risk of preterm birth by immunophenotyping in pregnant populations, and to elucidate the characteristics of immune subtypes and their relationships with preterm birth. Additionally, it sought to uncover the microbial composition and functional characteristics of immune states linked to preterm birth, and to evaluate the impact of bacterial interactions on the initiation of preterm birth.
Utilizing 16S rRNA sequencing data and local immune factor expression data from a publicly available longitudinal pregnancy cohort, we conducted immunophenotyping through unsupervised clustering of the immune factors. We compared the differences in vaginal microbiota richness, diversity, and composition between identified immune subtypes using α and β diversity analysis. Signature microbiotas were identified using LEfSe analysis, and functional pathway enrichment variations were analyzed using PICRUSt2. Bidirectional mediation analysis was employed to construct a network of mediating roles, and preliminary validation of the Microbial-Cytokine-Preterm Birth pathway was performed to explore the effects of microbial and immune characteristics on vaginal epithelial cell function.
Pregnant women were categorized into three immune subtypes based on local immune status. Microbial functional analysis identified 31 distinct functional pathways, six of which were downregulated in the preterm birth and excessive inflammatory response group. Significant differences in vaginal microbial diversity and composition were observed among pregnant women with different immune subtypes. Bidirectional mediation analysis revealed multiple intermediary roles in preterm birth, highlighting C3b/iC3b and IL-8 in mid-pregnancy and IgE and IgM in late pregnancy.
This study classified pregnant women into three immune subtypes, with the excessive inflammatory response subtype showing a higher predisposition to preterm birth. Mid-pregnancy immune status emerged as a key indicator of preterm birth risk, associated with the vaginal microbiome composition. Microorganisms affected the occurrence of preterm birth by modulating immune factor levels, with time-specific mediation roles observed. demonstrated potential in protecting against preterm birth by modulating vaginal immune status.
本研究旨在通过对孕妇群体进行免疫表型分析，确定与早产高风险相关的免疫状态，阐明免疫亚型的特征及其与早产的关系。此外，还试图揭示与早产相关的免疫状态的微生物组成和功能特征，并评估细菌相互作用对早产起始的影响。
利用公开可用的纵向妊娠队列中的16S rRNA测序数据和局部免疫因子表达数据，通过对免疫因子进行无监督聚类来进行免疫表型分析。我们使用α和β多样性分析比较了已识别的免疫亚型之间阴道微生物群丰富度、多样性和组成的差异。使用LEfSe分析确定标志性微生物群，并使用PICRUSt2分析功能通路富集变化。采用双向中介分析构建中介作用网络，并对微生物-细胞因子-早产通路进行初步验证，以探索微生物和免疫特征对阴道上皮细胞功能的影响。
根据局部免疫状态，孕妇被分为三种免疫亚型。微生物功能分析确定了31条不同的功能通路，其中6条在早产和过度炎症反应组中下调。不同免疫亚型的孕妇之间观察到阴道微生物多样性和组成存在显著差异。双向中介分析揭示了早产中的多种中介作用，突出了孕中期的C3b/iC3b和IL-8以及孕晚期的IgE和IgM。
本研究将孕妇分为三种免疫亚型，其中过度炎症反应亚型显示出更高的早产易感性。孕中期免疫状态成为早产风险的关键指标，与阴道微生物群组成有关。微生物通过调节免疫因子水平影响早产的发生，观察到具有时间特异性的中介作用。通过调节阴道免疫状态，在预防早产方面显示出潜力。
