Table 1_Exploring the composition of placental microbiome and its potential origin in preterm birth.docx

IntroductionFor years, the placenta was believed to be sterile, but recent studies reveal it hosts a unique microbiome. Despite these findings, significant questions remain about the origins of the placental microbiome and its effects on pregnancy and fetal health. Some studies suggest it may originate from the vaginal tract, while others indicate that oral bacteria can enter the maternal bloodstream and seed the placenta. However, research analyzing the vaginal, oral, and placental microbiomes within the same cohort is lacking. Additionally, it’s unclear whether the placental microbiome differs between healthy pregnancies and those with complications like preterm birth (PTB), which remains a leading cause of neonatal morbidity and mortality worldwide.
MethodsIn this study, we performed 16S rRNA gene sequencing to investigate the composition of the oral and placental microbiome in samples collected from 18 women who experienced PTB and 36 matched controls who delivered at term (TB), all of whom were part of the Molecular Signature in Pregnancy (MSP) study. We leveraged on the multisite microbiome sampling from the MSP participants and on our previously published vaginal microbiome data to investigate the potential origins of the placental microbiome and assess whether its composition varies between healthy and complicated pregnancies.
Results and DiscussionOur analysis revealed distinct profiles in the oral microbiome of PTB subjects compared to those who delivered at term. Specifically, we observed an increased abundance of Treponema maltophilum, Bacteroides sp, Mollicutes, Prevotella buccae, Leptotrichia, Prevotella_sp_Alloprevotella, in the PTB group. Importantly, Treponema maltophilum species showed higher abundance in the PTB group during the second trimester, suggesting its potential use as biomarkers. When we assessed the placenta microbiome composition, we found that Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria were the most dominant phyla. Interestingly, microorganisms such as Ureaplasma urealyticum were more abundant in PTB placenta samples. Our findings suggest that the placenta microbiome could originate from the oral or vaginal cavities, with a notable increase in the crosstalk between the vaginal and placental sites in cases of PTB. Specifically, our data revealed that in PTB cases, the placental microbiome exhibited a closer resemblance to the vaginal microbiome, whereas in term pregnancies, the placental microbiome was similar to the oral microbiome.

引言
长期以来，胎盘被认为是无菌环境，但近期研究表明其定植有独特的微生物组（microbiome）。尽管已有此类发现，但胎盘微生物组的起源及其对妊娠与胎儿健康的影响仍存在诸多关键待解问题。部分研究认为其可能源自阴道菌群，另有研究则指出口腔细菌可进入母体血液循环并定植于胎盘。然而，目前尚缺乏针对同一队列人群的阴道、口腔及胎盘微生物组开展的联合分析研究。此外，健康妊娠与早产（preterm birth, PTB）等并发症妊娠之间的胎盘微生物组是否存在差异仍不明确，而早产仍是全球范围内新生儿发病与死亡的首要诱因。

方法
本研究通过16S rRNA基因测序技术，对18名早产（preterm birth, PTB）产妇与36名足月分娩（term birth, TB）匹配对照产妇的口腔及胎盘微生物组组成展开分析，所有受试者均纳入妊娠分子特征（Molecular Signature in Pregnancy, MSP）研究队列。我们依托MSP队列受试者的多部位微生物组采样数据，以及此前已发表的阴道微生物组数据，探究胎盘微生物组的潜在起源，并评估健康妊娠与并发症妊娠之间其组成是否存在差异。

结果与讨论
分析结果显示，与足月分娩产妇相比，早产受试者的口腔微生物组具有显著不同的组成特征。具体而言，早产组中Treponema maltophilum、Bacteroides sp、Mollicutes、Prevotella buccae、Leptotrichia、Prevotella_sp_Alloprevotella的丰度显著升高。尤为重要的是，妊娠中期阶段，Treponema maltophilum在早产组中的丰度更高，提示该菌种可作为潜在的生物标志物。在对胎盘微生物组组成进行评估时，我们发现厚壁菌门（Firmicutes）、拟杆菌门（Bacteroidetes）、放线菌门（Actinobacteria）以及变形菌门（Proteobacteria）为胎盘菌群中的优势菌门。有趣的是，解脲脲原体（Ureaplasma urealyticum）等微生物在早产组的胎盘样本中丰度更高。本研究结果提示，胎盘微生物组可能源自口腔或阴道菌群，且在早产病例中，阴道与胎盘位点之间的菌群互作显著增强。具体而言，我们的数据显示，早产病例的胎盘微生物组与阴道微生物组更为相似，而足月妊娠者的胎盘微生物组则与口腔微生物组更为接近。