Abstract：
The existence of a placental microbiota is debated. The human placenta has historically been considered sterile and microbial colonization was associated with adverse pregnancy outcomes. Yet, recent DNA sequencing investigations reported a microbiota in typical human term placentas. However, this detected microbiota could represent background DNA or delivery-associated contamination. Using fifteen publicly available 16S rRNA gene datasets, existing data were uniformly re-analyzed with DADA2 to maximize comparability. While Amplicon Sequence Variants (ASVs) identified as Lactobacillus, a typical vaginal bacterium, were highly abundant and prevalent across studies, this prevalence disappeared after applying likely DNA contaminant removal to placentas from term cesarean deliveries. A six-study sub-analysis targeting the 16S rRNA gene V4 hypervariable region demonstrated that bacterial profiles of placental samples and technical controls share principal bacterial ASVs and that placental samples clustered primarily by study origin and mode of delivery. Contemporary DNA-based evidence does not support the existence of a placental microbiota.ImportanceEarly-gestational microbial influences on human development are unclear. By applying DNA sequencing technologies to placental tissue, bacterial DNA signals were observed, leading some to conclude that a live bacterial placental microbiome exists in typical term pregnancy. However, the low-biomass nature of the proposed microbiome and high sensitivity of current DNA sequencing technologies indicate that the signal may alternatively derive from environmental or delivery-associated bacterial DNA contamination. Here we address these alternatives with a re-analysis of 16S rRNA gene sequencing data from 15 publicly available placental datasets. After identical DADA2 pipeline processing of the raw data, subanalyses were performed to control for mode of delivery and environmental DNA contamination. Both environment and mode of delivery profoundly influenced the bacterial DNA signal from term-delivered placentas. Aside from these contamination-associated signals, consistency was lacking across studies. Thus, placentas delivered at term are unlikely to be the original source of observed bacterial DNA signals.
摘要：
胎盘微生物群的存在存在争议。人类胎盘历来被认为是无菌的，微生物定植与不良妊娠结局有关。然而，最近的DNA测序研究报道了典型的人类足月胎盘中的微生物群。然而,这种检测到的微生物群可能代表背景DNA或与递送相关的污染.使用15个公开可用的16SrRNA基因数据集，现有数据采用DADA2统一重新分析,以最大限度地提高可比性.虽然扩增子序列变异体（ASV）被鉴定为乳酸菌，一种典型的阴道细菌,在研究中非常丰富和普遍，在对足月剖宫产分娩的胎盘应用可能的DNA污染物去除后,这种患病率消失了.针对16SrRNA基因V4高变区的六项研究子分析表明，胎盘样品和技术对照的细菌谱共享主要的细菌ASV，并且胎盘样品主要通过研究来源和递送方式进行聚类。当代基于DNA的证据不支持胎盘微生物群的存在。重要性早期妊娠微生物对人类发育的影响尚不清楚。通过将DNA测序技术应用于胎盘组织，观察到细菌DNA信号，导致一些人得出结论，典型的足月妊娠中存在活的细菌胎盘微生物组。然而,所提出的微生物组的低生物量性质和当前DNA测序技术的高灵敏度表明，该信号可能可选地来自环境或递送相关的细菌DNA污染。在这里，我们通过重新分析来自15个公开可用的胎盘数据集的16SrRNA基因测序数据来解决这些替代方案。在对原始数据进行相同的DADA2流水线处理后，进行亚分析以控制递送方式和环境DNA污染.环境和分娩方式都深刻地影响了足月分娩胎盘的细菌DNA信号。除了这些与污染相关的信号,研究缺乏一致性。因此，足月分娩的胎盘不太可能是观察到的细菌DNA信号的原始来源。
