School of Health and Life Sciences, Teesside University, Middlesbrough, TS1 3BX, UK; National Horizons Centre, Teesside University, 38 John Dixon Lane, Darlington, DL1 1HG, UK.
Institute of Cellular Medicine, Newcastle University, Newcastle, NE2 4HH, UK.
Placenta. 2020 Feb;91:43-51. doi: 10.1016/j.placenta.2020.01.006. Epub 2020 Jan 21.
It is widely debated whether fetal membranes possess a genuine microbiome, and if bacterial presence and load is linked to inflammation. Chorioamnionitis is an inflammation of the fetal membranes. This research focussed on inflammatory diagnosed histological chorioamnionitis (HCA) and aimed to determine whether the bacterial load in fetal membranes correlates to inflammatory response, including histological staging and inflammatory markers in HCA.
Fetal membrane samples were collected from patients with preterm spontaneous labour and histologically phenotyped chorioamnionitis (HCA; n = 12), or preterm (n = 6) and term labour without HCA (n = 6). The bacterial profile of fetal membranes was analysed by sequencing the V4 region of the 16S rRNA gene. Bacterial load was determined using qPCR copy number/mg of tissue. The association between bacterial load and bacterial profile composition was assessed using correlation analysis.
Bacterial load was significantly greater within HCA amnion (p = 0.002) and chorion (p = 0.042), compared to preterm birth without HCA. Increased bacterial load was positively correlated with increased histological staging (p = 0.001) and the expression of five inflammatory markers; IL8, TLR1, TLR2, LY96 and IRAK2 (p=<0.050). Bacterial profiles were significantly different between membranes with and without HCA in amnion (p = 0.012) and chorion (p = 0.001), but no differences between specific genera were detected.
Inflammatory HCA is associated with infection and increased bacterial load in a dose response relationship. Bacterial load is positively correlated with HCA severity and the TLR signalling pathway. Further research should investigate the bacterial load threshold required to generate an inflammatory response in HCA.
人们广泛争论胎儿膜是否具有真正的微生物组，以及细菌的存在和负荷是否与炎症有关。绒毛膜羊膜炎是胎儿膜的炎症。本研究聚焦于炎症性诊断的组织学绒毛膜羊膜炎（HCA），旨在确定胎儿膜中的细菌负荷是否与炎症反应相关，包括 HCA 中的组织学分期和炎症标志物。
从患有自发性早产的患者中收集胎儿膜样本，并进行组织学表型绒毛膜羊膜炎（HCA；n=12）或早产（n=6）和无 HCA 的足月分娩（n=6）。通过对 16S rRNA 基因的 V4 区进行测序来分析胎儿膜的细菌谱。使用 qPCR 拷贝数/组织 mg 来确定细菌负荷。使用相关分析评估细菌负荷与细菌谱组成之间的关联。
与无 HCA 的早产相比，HCA 羊膜（p=0.002）和绒毛膜（p=0.042）中的细菌负荷显著更高。细菌负荷的增加与组织学分期的增加呈正相关（p=0.001），以及五种炎症标志物的表达呈正相关：IL8、TLR1、TLR2、LY96 和 IRAK2（p<0.050）。在羊膜（p=0.012）和绒毛膜（p=0.001）中，有 HCA 和无 HCA 的膜之间的细菌谱存在显著差异，但未检测到特定属之间的差异。
炎症性 HCA 与感染和剂量反应相关的细菌负荷增加有关。细菌负荷与 HCA 严重程度和 TLR 信号通路呈正相关。应进一步研究产生 HCA 炎症反应所需的细菌负荷阈值。
