The placental membrane microbiome is altered among subjects with spontaneous preterm birth with and without chorioamnionitis.
The placental membrane microbiome is altered among subjects with spontaneous preterm birth with and without chorioamnionitis.
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DOI：
10.1016/j.ajog.2016.01.193
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发表时间：
2016-05
影响因子：
9.8
通讯作者：
Aagaard KM
中科院分区：
文献类型：
--
作者：
Prince AL;Ma J;Kannan PS;Alvarez M;Gisslen T;Harris RA;Sweeney EL;Knox CL;Lambers DS;Jobe AH;Chougnet CA;Kallapur SG;Aagaard KM
早产（PTB）是新生儿发病率和死亡率的主要原因，并不罕见与绒毛膜炎。我们最近已经证明，胎盘含有一个独特的微生物组，其植物群与口腔群落相似。我们还表明这些胎盘微生物群与PTB，产前感染史和母亲体重过度增加有关。基于这些先前的观察结果，我们假设胎盘膜将保留一个微生物群落，该群落将与早产和绒毛膜炎相关。在目前的研究中，我们的目的是使用最先进的全基因组鸟枪宏基因组学研究在存在和不存在绒毛膜炎和/或输卵管炎的情况下，胎盘膜微生物组与PTB相关的差异。这是一项包含6个巢式自然分娩队列（n = 9-15例受试者/队列）的横断面分析：未发生绒毛膜炎的足月妊娠、发生绒毛膜炎的足月妊娠、未发生绒毛膜炎的早产、发生轻度绒毛膜炎的早产、发生重度绒毛膜炎的早产以及发生绒毛膜炎和精索炎的早产。采用Redline标准进行组织学分析，并分析脐带血中的炎性细胞因子。从分娩时收集的无菌拭子中提取胎盘膜的DNA，并在Illumina HiSeq平台上进行全基因组鸟枪测序。用MG-RAST（即使用子系统技术的宏基因组快速注释）和R.受试者根据分娩时的胎龄和组织学绒毛膜炎的独立评分被分配到队列中。我们发现患有严重绒毛膜羊水炎和脐带炎的早产儿脐带血炎症细胞因子增加。有趣的是，尽管胎盘膜微生物组的改变与组织学绒毛膜炎的严重程度相关（排列多变量方差分析P = 0.005），但β-地塞米松或抗生素治疗均未观察到影响。在患有绒毛膜炎的早产儿中，我们发现泌尿生殖道和口腔粘膜细菌的丰度很高。微生物组的这些改变伴随着微生物代谢途径的显著变化（P <0.05），这些代谢途径在葡萄糖喂养的磷酸戊糖途径（足月受试者）或甘油磷脂代谢以及铁载体组非核糖体肽的生物合成（早产受试者）中很重要。与我们和其他人以前的研究结果一致，经历自发性PTB的女性携带胎盘微生物群，这些微生物群因绒毛膜炎的严重程度而进一步不同。综合性元基因组分析揭示了不同细菌代谢途径的显著差异，我们推测这可能有助于伴有或不伴有严重绒毛膜炎的早产风险。
Preterm birth (PTB) is a leading cause of neonatal morbidity and mortality and is not uncommonly associated with chorioamnionitis. We recently have demonstrated that the placenta harbors a unique microbiome with similar flora to the oral community. We also have shown an association of these placental microbiota with PTB, history of antenatal infection, and excess maternal weight gain. On the basis of these previous observations, we hypothesized that the placental membranes would retain a microbiome community that would vary in association with preterm birth and chorioamnionitis. In the current study, we aimed to examine the differences in the placental membrane microbiome in association with PTB in both the presence and absence of chorioamnionitis and/ or funisitis using state-of-the-science whole-genome shotgun metagenomics. This was a cross-sectional analysis with 6 nested spontaneous birth cohorts (n = 9–15 subjects/cohort): Term gestations without chorioamnionitis, term with chorioamnionitis, preterm without chorioamnionitis, preterm with mild chorioamnionitis, preterm with severe chorioamnionitis, and preterm with chorioamnionitis and funisitis. Histologic analysis was performed with Redline's criteria, and inflammatory cytokines were analyzed in the cord blood. DNA from placental membranes was extracted from sterile swabs collected at delivery, and whole-genome shotgun sequencing was performed on the Illumina HiSeq platform. Filtered microbial DNA sequences were annotated and analyzed with MG-RAST (ie, Metagenomic Rapid Annotations using Subsystems Technology) and R. Subjects were assigned to cohorts on the basis of gestational age at delivery and independent scoring of histologic chorioamnionitis. We found that preterm subjects with severe chorioamnionitis and funisitis had increases in cord blood inflammatory cytokines. Of interest, although the placental membrane microbiome was altered in association with severity of histologic chorioamnionitis (permutational multivariate analysis of variance P = .005), there was no observable impact with either beta-methasone or antibiotic treatment. In preterm subjects with chorioamnionitis, we found a high abundance of both urogenital and oral commensal bacteria. These alterations in the microbiome were accompanied by significant variation (P < .05) in microbial metabolic pathways important in the glucose-fed pentose phosphate pathway (term subjects), or glycerophopholipid metabolism, and the biosynthesis of the siderophore group nonribosomal peptides (preterm subjects). Consistent with ours and others previous findings, women who experienced spontaneous PTB harbor placental microbiota that further differed by severity of chorioamnionitis. Integrative meta-genomic analysis revealed significant variation in distinct bacterial metabolic pathways, which we speculate may contribute to risk of preterm birth with and without severe chorioamnionitis.