Objective Pre-eclampsia (PE) is one of the malignant metabolic diseases that complicate pregnancy. Gut dysbiosis has been identified for causing metabolic diseases, but the role of gut microbiome in the pathogenesis of PE remains unknown. Design We performed a case–control study to compare the faecal microbiome of PE and normotensive pregnant women by 16S ribosomal RNA (rRNA) sequencing. To address the causative relationship between gut dysbiosis and PE, we used faecal microbiota transplantation (FMT) in an antibiotic-treated mouse model. Finally, we determined the microbiome translocation and immune responses in human and mouse placental samples by 16S rRNA sequencing, quantitative PCR and in situ hybridisation. Results Patients with PE showed reduced bacterial diversity with obvious dysbiosis. Opportunistic pathogens, particularly Fusobacterium and Veillonella, were enriched, whereas beneficial bacteria, including Faecalibacterium and Akkermansia, were markedly depleted in the PE group. The abundances of these discriminative bacteria were correlated with blood pressure (BP), proteinuria, aminotransferase and creatinine levels. On successful colonisation, the gut microbiome from patients with PE triggered a dramatic, increased pregestational BP of recipient mice, which further increased after gestation. In addition, the PE-transplanted group showed increased proteinuria, embryonic resorption and lower fetal and placental weights. Their T regulatory/helper-17 balance in the small intestine and spleen was disturbed with more severe intestinal leakage. In the placenta of both patients with PE and PE-FMT mice, the total bacteria, Fusobacterium, and inflammatory cytokine levels were significantly increased. Conclusions This study suggests that the gut microbiome of patients with PE is dysbiotic and contributes to disease pathogenesis.

中文翻译：

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肠道菌群失调通过细菌易位诱导先兆子痫的发展

目的先兆子痫（PE）是一种复杂的妊娠恶性代谢疾病。肠道菌群失调已被确定会导致代谢疾病，但肠道微生物组在 PE 发病机制中的作用仍不清楚。设计 我们进行了一项病例对照研究，通过 16S 核糖体 RNA (rRNA) 测序来比较 PE 和血压正常孕妇的粪便微生物组。为了解决肠道菌群失调与 PE 之间的因果关系，我们在抗生素治疗的小鼠模型中使用了粪便微生物群移植 (FMT)。最后，我们通过 16S rRNA 测序、定量 PCR 和原位杂交确定了人和小鼠胎盘样本中的微生物组易位和免疫反应。结果 PE 患者的细菌多样性降低，菌群失调明显。机会性病原体，特别是梭杆菌和韦永氏菌被富集，而有益菌，包括粪杆菌和阿克曼氏菌，在 PE 组中显着减少。这些鉴别细菌的丰度与血压 (BP)、蛋白尿、氨基转移酶和肌酐水平相关。成功定植后，PE 患者的肠道微生物群会引发受体小鼠的妊娠前血压急剧升高，并在妊娠后进一步升高。此外，PE 移植组显示出蛋白尿增加、胚胎吸收增加以及胎儿和胎盘重量降低。他们在小肠和脾脏中的 T 调节/辅助 17 平衡因更严重的肠漏而受到干扰。在 PE 和 PE-FMT 小鼠的胎盘中，总细菌梭杆菌、和炎性细胞因子水平显着升高。结论 这项研究表明 PE 患者的肠道微生物群是生态失调的，并有助于疾病的发病机制。