Early-Onset Preeclampsia Is Associated With Gut Microbial Alterations in Antepartum and Postpartum Women.

Li-Juan Lv,Yu-Nan Wang,Lena Yao,Cheng Tian,Ai-Hua Yin,Xin Zhou,Sheng-Hui Li,Hui Li,Tian-Wen He,Wei He,Zhi-Cheng Zhong,Hong-Li Duan,Shao-Chuan Li,Min-Chai Chen

doi:10.3389/fcimb.2019.00224

Abstract

Background: Imbalances in gut microbiota composition are linked to hypertension, host metabolic abnormalities, systemic inflammation, and other conditions. In the present study, we examined the changes of gut microbiota in women with early-onset preeclampsia (PE) and in normotensive, uncomplicated pregnant women during late pregnancy and at 1 and 6 weeks postpartum.Methods: Gut microbiota profiles of women with PE and healthy pregnant women in the third trimester and at 1 and 6 weeks postpartum were assessed by 16S rRNA gene amplicon sequencing. Plasma levels of interleukin-6 (IL-6), intestinal fatty acid-binding protein (I-FABP), zonulin, and lipopolysaccharide (LPS) were measured in the third trimesters.Results: At the genus level, 8 bacterial genera were significantly enriched in the antepartum samples of PE patients compared to healthy controls, of which Blautia, Ruminococcus2, Bilophila, and Fusobacterium represented the major variances in PE microbiomes. Conversely, 5 genera, including Faecalibacterium, Gemmiger, Akkermansia, Dialister, and Methanobrevibacter, were significantly depleted in antepartum PE samples. Maternal blood pressure and liver enzyme levels were positively correlated to the PE-enriched genera such as Anaerococcus, Ruminococcus2, Oribacterium, and Bilophila, while the fetal features (e.g., Apgar score and newborn birth weight) were positively correlated with PE-depleted genera and negatively correlated with PE-enriched genera. Moreover, maternal blood IL-6 level was positively associated with gut Bilophila and Oribacterium, whereas LPS level was negatively associated with Akkermansia. In terms of postpartum women, both the gut microbial composition and the PE-associated microbial alterations were highly consistent with those of the antepartum women.Conclusion: PE diagnosed in the third trimester of pregnancy is associated with a disrupted gut microbiota composition compared with uncomplicated pregnant women, which are associated with maternal clinical features (blood pressure level and liver dysfunction) and newborn birth weight. Moreover, these antepartum alterations in gut microbiota persisted 6 weeks postpartum.

Highlights

Preeclampsia (PE), the second leading cause of maternal mortality worldwide (Huppertz, 2008; Ghulmiyyah and Sibai, 2012; Mol et al, 2016), is characterized by severe hypertension and multiple organ damage (Brown et al, 2018), and it can result in fetal intrauterine growth retardation, premature birth, or fetal death (Kovo et al, 2015)
We identified the bacterial taxa associated with preeclampsia and revealed dynamic changes in the gut microbiota of patients from late pregnancy to postpartum
78 cases newly diagnosed with preeclampsia with severe effect in their third trimesters were categorized as the PE group, while 72 normotensive and uncomplicated women were designated as the normal controls (NC group)

Summary

Introduction

Preeclampsia (PE), the second leading cause of maternal mortality worldwide (Huppertz, 2008; Ghulmiyyah and Sibai, 2012; Mol et al, 2016), is characterized by severe hypertension and multiple organ damage (Brown et al, 2018), and it can result in fetal intrauterine growth retardation, premature birth, or fetal death (Kovo et al, 2015). Gut microbiota has profound effects on regulating host metabolism (Pedersen et al, 2016; Liu R. et al, 2017) It plays an important role in blood pressure elevation during pregnancies (the hallmark of preeclampsia) (GomezArango et al, 2016a). The above immune responses play a leading role in two main pathophysiological processes occurring in PE patients: (1) poor trophoblastic invasion resulted from the altered production of immunoregulatory cytokines and angiogenic factors and (2) a systemic inflammatory response (Laresgoiti-Servitje, 2013). These evidences highlight the potential and important association between gestational gut microbiota and preeclampsia. We examined the changes of gut microbiota in women with early-onset preeclampsia (PE) and in normotensive, uncomplicated pregnant women during late pregnancy and at 1 and 6 weeks postpartum

Methods

Results

Discussion

Conclusion