Gut dysbiosis induces the development of pre-eclampsia through bacterial translocation

• Published in: Gut Vol. 69; no. 3; pp. 513 - 522
• Main Authors: Chen, Xia, Li, Pan, Liu, Mian, Zheng, Huimin, He, Yan, Chen, Mu-Xuan, Tang, Wenli, Yue, Xiaojing, Huang, Yongxin, Zhuang, Lingling, Wang, Zhijian, Zhong, Mei, Ke, Guibao, Hu, Haoyue, Feng, Yinglin, Chen, Yun, Yu, Yanhong, Zhou, Hongwei, Huang, Liping
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd and British Society of Gastroenterology 01.03.2020; BMJ Publishing Group LTD
• Subjects: Animals; Antibiotics; Antigens; Bacteria; Bacterial Translocation; Blood Pressure; Case-Control Studies; CD4 Lymphocyte Count; Chemokines - genetics; Creatinine; Creatinine - blood; Cytokines - genetics; Digestive system; Discriminant analysis; Disease; Disease Models, Animal; Dysbacteriosis; Dysbiosis - complications; Dysbiosis - physiopathology; Embryos; Faecalibacterium; Feces - microbiology; Female; Fetal Resorption - microbiology; Fetuses; Flow cytometry; Fusobacteria; Fusobacterium; Gastrointestinal Microbiome; Gastrointestinal tract; Gene expression; Gestation; Gut microbiota; Gynecology; Hospitals; Humans; Hybridization; Hypertension; Immune response; Immunoglobulins; immunology; Inflammation; Insulin resistance; intestinal bacteria; intestinal barrier function; Intestinal microflora; Intestine, Small - immunology; Metabolic disorders; Metabolic syndrome; Mice; Microbiomes; Microbiota; Obstetrics; Opportunist infection; Pathogenesis; Placenta; Placenta - immunology; Placenta - metabolism; Placenta - microbiology; Pre-eclampsia; Pre-Eclampsia - microbiology; Pre-Eclampsia - physiopathology; Preeclampsia; Pregnancy; Probiotics; Proteins; Proteinuria; Proteinuria - urine; RNA, Messenger - metabolism; rRNA 16S; Small intestine; Spleen; Statistical analysis; Studies; T-Lymphocytes, Regulatory; Taxonomy; Th17 Cells; Transplantation; Urine; Veillonella; United States > US; China; California; bacterial translocation; intestinal bacteria; intestinal barrier function; immunology
• ISSN: 0017-5749; 1468-3288; 1468-3288
• DOI: 10.1136/gutjnl-2019-319101

ObjectivePre-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.DesignWe 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.ResultsPatients 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.ConclusionsThis study suggests that the gut microbiome of patients with PE is dysbiotic and contributes to disease pathogenesis.