Short-chain fatty acids accompanying changes in the gut microbiome contribute to the development of hypertension in patients with preeclampsia.

Yanling Chang,Chuan Wang,Lei Chen,Yu Zhang,Wen Di,Qiong Zhou,Yunyan Chen

doi:10.1042/cs20191253

Abstract

Preeclampsia (PE) is regarded as a pregnancy-associated hypertension disorder that is related to excessive inflammatory responses. Although the gut microbiota (GM) and short-chain fatty acids (SCFAs) have been related to hypertension, their effects on PE remain unknown. We determined the GM abundance and faecal SCFA levels by 16S ribosomal RNA (rRNA) sequencing and gas chromatography, respectively, using faecal samples from 27 patients with severe PE and 36 healthy, pregnant control subjects. We found that patients with PE had significantly decreased GM diversity and altered GM abundance. At the phylum level, patients with PE exhibited decreased abundance of Firmicutes albeit increased abundance of Proteobacteria; at the genus level, patients with PE had lower abundance of Blautia, Eubacterium_rectale, Eubacterium_hallii, Streptococcus, Bifidobacterium, Collinsella, Alistipes, and Subdoligranulum, albeit higher abundance of Enterobacter and Escherichia_Shigella. The faecal levels of butyric and valeric acids were significantly decreased in patients with PE and significantly correlated with the above-mentioned differential GM abundance. We predicted significantly increased abundance of the lipopolysaccharide (LPS)-synthesis pathway and significantly decreased abundance of the G protein-coupled receptor (GPCR) pathway in patients with PE, based on phylogenetic reconstruction of unobserved states (PICRUSt). Finally, we evaluated the effects of oral butyrate on LPS-induced hypertension in pregnant rats. We found that butyrate significantly reduced the blood pressure (BP) in these rats. In summary, we provide the first evidence linking GM dysbiosis and reduced faecal SCFA to PE and demonstrate that butyrate can directly regulate BP in vivo, suggesting its potential as a therapeutic agent for PE.

Highlights

Preeclampsia (PE) is diagnosed as new-onset hypertension with a systolic blood pressure (BP) over 140 mm Hg and/or a diastolic BP over 90 mm Hg after 20 weeks of gestation, combined with proteinuria or new onset of thrombocytopaenia, renal insufficiency, impaired liver function, pulmonary oedema, or cerebral or visual symptoms [1]
We found that the abundance of the LPS biosynthesis and G protein-coupled receptor (GPCR) pathways was correlated with differential gut microbiota (GM) abundance, suggesting that these two pathways may be involved in GM dysbiosis-related PE
We observed, for the first time, a link between GM dysbiosis and simultaneously reduced faecal short-chain fatty acid (SCFA) with PE, which suggests that GM and SCFA might cooperatively contribute to PE

Summary

Introduction

Preeclampsia (PE) is diagnosed as new-onset hypertension with a systolic blood pressure (BP) over 140 mm Hg and/or a diastolic BP over 90 mm Hg after 20 weeks of gestation, combined with proteinuria or new onset of thrombocytopaenia, renal insufficiency, impaired liver function, pulmonary oedema, or cerebral or visual symptoms [1]. The pathogenesis of PE is different from that of primary hypertension [4]. Placental insufficiency is generally thought to play a central role in the pathogenesis of PE, it cannot explain all occurrences of the disease [5]. It was reported that components of the gut microbiota (GM) are related to hypertension [6]. A shift in the gut microbial genera is associated with the pathophysiological and immune statuses of high

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