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Gut dysbiosis induces the development of pre-eclampsia through bacterial translocation.
- Source :
-
Gut [Gut] 2020 Mar; Vol. 69 (3), pp. 513-522. Date of Electronic Publication: 2020 Jan 03. - Publication Year :
- 2020
-
Abstract
- 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.<br />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.<br />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.<br />Conclusions: This study suggests that the gut microbiome of patients with PE is dysbiotic and contributes to disease pathogenesis.<br />Competing Interests: Competing interests: None declared.<br /> (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)
- Subjects :
- Animals
Blood Pressure
CD4 Lymphocyte Count
Case-Control Studies
Chemokines genetics
Creatinine blood
Cytokines genetics
Disease Models, Animal
Dysbiosis physiopathology
Faecalibacterium
Feces microbiology
Female
Fetal Resorption microbiology
Fusobacteria
Humans
Intestine, Small immunology
Mice
Placenta metabolism
Pre-Eclampsia physiopathology
Pregnancy
Proteinuria urine
RNA, Messenger metabolism
T-Lymphocytes, Regulatory
Th17 Cells
Veillonella
Bacterial Translocation
Dysbiosis complications
Gastrointestinal Microbiome
Placenta immunology
Placenta microbiology
Pre-Eclampsia microbiology
Subjects
Details
- Language :
- English
- ISSN :
- 1468-3288
- Volume :
- 69
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Gut
- Publication Type :
- Academic Journal
- Accession number :
- 31900289
- Full Text :
- https://doi.org/10.1136/gutjnl-2019-319101