Early-Onset Preeclampsia Is Associated With Gut Microbial Alterations in Antepartum and Postpartum Women - PubMed (original) (raw)
doi: 10.3389/fcimb.2019.00224. eCollection 2019.
Sheng-Hui Li 3, Shao-Chuan Li 3, Zhi-Cheng Zhong 2, Hong-Li Duan 4, Cheng Tian 3, Hui Li 4, Wei He 2, Min-Chai Chen 2, Tian-Wen He 2, Yu-Nan Wang 2, Xin Zhou 5, Lena Yao 6, Ai-Hua Yin 2
Affiliations
- PMID: 31297341
- PMCID: PMC6608563
- DOI: 10.3389/fcimb.2019.00224
Early-Onset Preeclampsia Is Associated With Gut Microbial Alterations in Antepartum and Postpartum Women
Li-Juan Lv et al. Front Cell Infect Microbiol. 2019.
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.
Keywords: 16S rRNA gene sequencing; gut microbiota; microbial dysbiosis; preeclampsia; pregnancy.
Figures
Figure 1
Overview of the gut microbial community in PE patients and healthy controls. (A) Summary of the taxonomic assignment of the OTUs. Inner circle, the percentage of OTUs that assigned into a taxon at the species, genus, family, order, class, and phylum levels. Outer circle, the percentage of representing sequences of the OTUs at all taxonomic levels. (B) Host factors that significantly affected the gut microbiota. The 12 factors associated with the variation of the gut microbiota at the OTU level are shown. Bar plots indicate the explained variation (effect size) of each factor at the OTU level (left panel) and genus level (right panel). **, permutated P < 0.01; *, permutated P < 0.05. (C) dbRDA plot based on the Bray-Curtis distances between microbial genera, revealing PE microbial dysbiosis at the antepartum, 1 and 6 weeks postpartum periods. Patient and control samples were mainly separated in the primary constrained axis (PE separation), and samples at different time points were mainly separated in the second constrained axis (time point separation). Lines connect samples (colored points) in the same group, and circles cover samples near the center of gravity for each group. Genera (yellow squares) as the main contributors are plotted by their loadings in these two components. (D) Constitution of enterotypes in all groups. _P_-values between PE patients and healthy controls at three time points were calculated based on Fisher's exact test.
Figure 2
Difference of gut microbiota between PE patients and healthy controls. (A) Boxplot shows the significantly different genera between patients and controls. Genera with P < 0.05 (Wilcoxon rank-sum test) of samples at antepartum are shown. The boxes represent the interquartile range (IQR) between the first and third quartiles and the line inside represents the median. The whiskers denote the lowest and highest values within 1.5 times IQR from the first and third quartiles, respectively. **(B)** The PE-associated genera and species of samples at antepartum, and their tendencies in samples at 1 and 6 weeks postpartum. The bar lengths indicate the Z-score of a genus or species at different time points, and the colors represent enrichment in patients (red, Z-score > 0) or controls (blue, Z-score < 0). (C) ROC analysis for classification of PE status by the relative abundances of PE-associated genera, assessed by AUC.
Figure 3
Correlation between PE-associated genera and the host parameters. The heatmap panel shows the Spearman correlation coefficient between the genera (text color: red, enriched in PE patients; blue, enriched in healthy controls) and host parameters. Significance levels in correlation tests are denoted: +,q < 0.10; *,q < 0.05.
Figure 4
Correlation between PE-associated genera and functional modules. The heatmap panel shows the Spearman correlation coefficient between the genera and KEGG functional modules. Text color for genera and modules: red, enriched in PE patients; blue, enriched in healthy controls. Significance levels in correlation tests are denoted: +,P < 0.05; *,P < 0.01.
Figure 5
Longitudinal comparison of gut microbial diversity and composition between antepartum, 1 and 6 weeks postpartum. (A) Change in alpha diversity from the antepartum to 1 and 6 weeks postpartum. The boxes represent the interquartile range (IQR) between the first and third quartiles and the line inside represents the median. The whiskers denote the lowest and highest values within 1.5 times IQR from the first and third quartiles, respectively. Pearson correlation coefficient of samples between two time points was calculated, and _P_-value was tested using the correlation test. (B) Procrustes analysis reveals the covariation between samples at the antepartum, 1 and 6 weeks postpartum periods.
Figure 6
A schematic diagram showing the PE-associated bacteria and functions that had predicted effects on the host disease, clinical status, and metabolism. The PE-enriched species and functions are shown in the left red columns, and the PE-depleted species and functions are shown in the right blue columns. Center boxes show the host properties. Lines connect the PE-associated species and host properties with potential associations, while the dotted lines indicate the correlations which were identified in this study.
References
- American College of Obstetricians and Gynecologists and Task Force on Hypertension in Pregnancy (2013). Hypertension in pregnancy. Report of the American college of obstetricians and gynecologists' task force on hypertension in pregnancy. Obstet. Gynecol. 122, 1122–1131. 10.1097/01.AOG.0000437382.03963.88 - DOI - PubMed
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