背景:早产,新生儿死亡的主要原因,与母体牙周病和胎盘中口腔病原体的存在有关。然而,支撑这一联系的机制尚不清楚。这项研究旨在确定胎盘微生物群的起源,并探讨分娩并发症与胎盘微生物基序的免疫识别之间的关系。视频摘要方法:唾液,牌匾,血清,在130个足月(FT)期间收集胎盘,早产(PT),或早产并发先兆子痫(PTPE)分娩并进行全基因组shot弹枪测序。实时定量PCR用于测量胎盘样品中Toll样受体(TLR)1-10的表达。采用来源追踪来追踪胎盘微生物群的起源。
结果:我们在胎盘中发现了10,007个功能注释的基因,代表420个分类群,这些基因不能归因于污染。胎盘微生物组成是妊娠并发症的最大鉴别因素,超过高血压,BMI,吸烟,和产妇年龄。在该微生物数据集上训练的机器学习算法预测PTPE和PT,错误率分别为4.05%和8.6%(分类法)和6.21%和7.38%(功能)。Logistic回归显示分娩并发症的几率高出32%(95%CI2.8%,81%)在调整母亲吸烟状况后,香农多样性指数每增加一次IQR,产妇年龄,还有Gravida.我们还发现了在三组中检测RNA和DNA抗原的TLRs的不同表达模式,PTPE和PT组TLR9显著上调,同时TLR7下调,以及微生物基因和这些TLR之间的紧密相关网络。70-82%的胎盘微生物群被追踪到血清,因此被追踪到唾液和龈下微生物群。PTPE和PT组的口腔和血清微生物组显示出铁转运基因的显著富集,exosome,附着力,仲裁感应,脂多糖,生物膜,和类固醇降解。
结论:在横截面分析的范围内,我们发现有证据表明口腔细菌可能通过血清转移到胎盘,并触发能够诱导胎盘血管病变的免疫信号通路。这也许可以解释,在某种程度上,有牙周病的妇女中产科综合征的发病率较高。
BACKGROUND: Pre-term birth, the leading cause of neonatal mortality, has been associated with maternal periodontal disease and the presence of oral pathogens in the placenta. However, the mechanisms that underpin this link are not known. This investigation aimed to identify the origins of placental microbiota and to interrogate the association between parturition complications and immune recognition of placental microbial motifs. Video Abstract METHODS: Saliva, plaque, serum, and placenta were collected during 130 full-term (FT), pre-term (PT), or pre-term complicated by pre-eclampsia (PTPE) deliveries and subjected to whole-genome shotgun sequencing. Real-time quantitative PCR was used to measure toll-like receptors (TLR) 1-10 expression in placental samples. Source tracking was employed to trace the origins of the placental microbiota.
RESULTS: We discovered 10,007 functionally annotated genes representing 420 taxa in the placenta that could not be attributed to contamination. Placental microbial composition was the biggest discriminator of pregnancy complications, outweighing hypertension, BMI, smoking, and maternal age. A machine-learning algorithm trained on this microbial dataset predicted PTPE and PT with error rates of 4.05% and 8.6% (taxonomy) and 6.21% and 7.38% (function). Logistic regression revealed 32% higher odds of parturition complication (95% CI 2.8%, 81%) for every IQR increase in the Shannon diversity index after adjusting for maternal smoking status, maternal age, and gravida. We also discovered distinct expression patterns of TLRs that detect RNA- and DNA-containing antigens in the three groups, with significant upregulation of TLR9, and concomitant downregulation of TLR7 in PTPE and PT groups, and dense correlation networks between microbial genes and these TLRs. 70-82% of placental microbiota were traced to serum and thence to the salivary and subgingival microbiomes. The oral and serum microbiomes of PTPE and PT groups displayed significant enrichment of genes encoding iron transport, exosome, adhesion, quorum sensing, lipopolysaccharide, biofilm, and steroid degradation.
CONCLUSIONS: Within the limits of cross-sectional analysis, we find evidence to suggest that oral bacteria might translocate to the placenta via serum and trigger immune signaling pathways capable of inducing placental vascular pathology. This might explain, in part, the higher incidence of obstetric syndromes in women with periodontal disease.