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Original research
Gut dysbiosis induces the development of pre-eclampsia through bacterial translocation
  1. Xia Chen1,
  2. Pan Li2,
  3. Mian Liu1,
  4. Huimin Zheng2,3,
  5. Yan He2,
  6. Mu-Xuan Chen2,
  7. Wenli Tang2,
  8. Xiaojing Yue1,
  9. Yongxin Huang1,
  10. Lingling Zhuang4,
  11. Zhijian Wang1,
  12. Mei Zhong1,
  13. Guibao Ke5,
  14. Haoyue Hu1,
  15. Yinglin Feng1,
  16. Yun Chen1,
  17. Yanhong Yu1,
  18. Hongwei Zhou2,
  19. Liping Huang1
  1. 1 Department of Obstetrics and Gynecology, Southern Medical University Nanfang Hospital, Guangzhou, Guangdong, China
  2. 2 Microbiome Medicine Center, Division of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China
  3. 3 Microbiome Research Centre, St George and Sutherland Clinical School, University of New South Wales, Sydney, New South Wales, Australia
  4. 4 Department of Obstetrics and Gynecology, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
  5. 5 Department of Internal Medicine, Affiliated Hospital, Chengdu University, Chengdu, Sichuan, China
  1. Correspondence to Professor Liping Huang, Department of Obstetrics and Gynecology, Southern Medical University Nanfang Hospital, Guangzhou, Guangdong, China; lphuang2006{at}126.com; Professor Hongwei Zhou, Microbiome Medicine Center, Division of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China; hzhou{at}smu.edu.cn; Professor Yanhong Yu, Department of Obstetrics and Gynecology, Southern Medical University Nanfang Hospital, Guangzhou, Guangdong, China; yuyh1010{at}hotmail.com

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.

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.

  • intestinal bacteria
  • intestinal barrier function
  • bacterial translocation
  • immunology
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Footnotes

  • XC, PL and ML contributed equally.

  • Contributors YY, HZ, LH, YH and XC designed the study and prepared the manuscript. XC, ML, XY, YF, LZ, YC, YH, GK, MZ and ZW collected the samples and conducted the experiments. PL, HZ, YH, XC, WT and HH analysed the data. All authors approved the final version of the manuscript.

  • Funding This investigation was financially supported by the National Natural Science Foundation of China (81925026, 81703078, 81771609, 81800746 and 31570497), the National Key Research and Development Program of China (2019YFA0802300), the Natural Science Foundation of Guangdong Province (2017A010105025) and China Postdoctoral Science Foundation (2018M633077).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval Nanfang Hospital.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available in a public, open access repository.

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