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作者

Jiajia Jin, Liaomei Gao, Xiuli Zou, Yun Zhang, Zhijian Zheng, Xinjie Zhang, Jiaxuan Li, Zhenyu Tian, Xiaowei Wang, Junfei Gu, Cheng Zhang, Tiejun Wu, Zhe Wang, Qunye Zhan

作者单位

Affiliations ¹ Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences (J.J., Y.Z., Z.Z., Z.T., X.W., C.Z., Q.Z.). ² State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine (J.J., Y.Z., Z.Z., Z.T., X.W., C.Z., Q.Z.). ³ Department of Cardiology, Qilu Hospital of Shandong University, Jinan, China (J.J., Y.Z., Z.Z., Z.T., X.W., C.Z., Q.Z.). ⁴ Division of Geriatrics, Department of Endocrinology, Shandong Provincial Hospital, Shandong University, Jinan, China (L.G., J.L., J.G., Z.W.). ⁵ Maternal and child health care hospital of Shandong province, Shandong University, Jinan, China (L.G.). ⁶ Intensive Care Unit, Liaocheng People's Hospital, China (X.Z., T.W.). ⁷ Department of Biology, University College London, United Kingdom (X.Z.). ⁸ Cardiovascular Disease Research Center of Shandong First Medical University, Central Hospital Affiliated to Shandong First Medical University, Jinan, China (Q.Z.).

刊名

Circulation research

年份

2022

ISSN

1524-4571

关键词

dysbiosis gut microbiota hypertension placenta preeclampsia.

摘要

Background: Preeclampsia is one of the leading causes of maternal and perinatal morbidity and is characterized by hypertension, inflammation, and placental dysfunction. Gut microbiota plays key roles in inflammation and hypertension. However, its roles and mechanisms in preeclampsia have not been fully elucidated. Methods: 16S rRNA gene sequencing and targeted metabolomics were conducted on stool samples from 92 preeclamptic patients and 86 normal late-pregnant women. Then, fecal microbiota tran...更多

Background: Preeclampsia is one of the leading causes of maternal and perinatal morbidity and is characterized by hypertension, inflammation, and placental dysfunction. Gut microbiota plays key roles in inflammation and hypertension. However, its roles and mechanisms in preeclampsia have not been fully elucidated. Methods: 16S rRNA gene sequencing and targeted metabolomics were conducted on stool samples from 92 preeclamptic patients and 86 normal late-pregnant women. Then, fecal microbiota transplantation and in vitro and in vivo functional experiments were performed to explore the roles and mechanisms of gut microbiota in preeclampsia development. Results: We revealed the gut microbiota dysbiosis in preeclamptic patients, including significant reductions in short-chain fatty acid-producing bacteria and short-chain fatty acids. The gut microbiota of preeclamptic patients significantly exacerbated pathologies and symptoms of preeclamptic rats, whereas the gut microbiota of healthy pregnant women had significant protective effects. Akkermansia muciniphila, propionate, or butyrate significantly alleviated the symptoms of preeclamptic rats. Mechanistically, they significantly promoted autophagy and M2 polarization of macrophages in placental bed, thereby suppressing inflammation. Propionate also significantly promoted trophoblast invasion, thereby improved spiral arterial remodeling. Additionally, we identified a marker set consisting of Akkermansia, Oscillibacter, and short-chain fatty acids that could accurately diagnose preeclampsia. Conclusions: Our study revealed that gut microbiota dysbiosis is an important etiology of preeclampsia. Gut microbiota and their active metabolites have great potential for the treatment and diagnosis of preeclampsia. Our findings enrich the gut-placenta axis theory and contribute to the development of microecological products for preeclampsia.收起

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