Gut microbiota changes in preeclampsia, abnormal placental growth and healthy pregnant women

Abstract

Background: Preeclampsia (PE) is a condition of high blood pressure that is usually concurrent with proteinuria in pregnancy. PE complicates the management of both maternal and fetal health and contributes to most adverse pregnancy outcomes, but the mechanism underlying the development of PE remains unclear. In this study, we performed a case-control study to compare the gut microbiota of PE (n = 26), abnormal placental growth (APG, n = 25) and healthy pregnant women (n = 28) and analyzed the potential pathogenic role of gut microbiota in PE progression.

Results: The clinical pathophysiological state did not affect the bacterial diversity, while the compositions of the gut microbiota were significantly altered in both the PE and APG groups compared with healthy pregnant women. At the phylum level, TM7 was significantly increased in women with APG. Heterogeneity was observed at the genus level, especially in genera with positive LDA scores, suggesting the stage-dependent effect of gut microbiota on the development of PE. The beneficial bacterium Lactobacillus was markedly depleted in the PE and APG groups but was only correlated with blood pressure (BP) and proteinuria levels in the PE group. Two different bacterial taxa belonged to Lactobacillus showed different correlations (OTU255 and OTU784 were significantly related to PE and APG, respectively).

Conclusions: Our results indicated that shifts in the gut microbiota might occur from the early stages of the development of PE, which is of possible etiological and therapeutic importance.

Keywords: Gut microbiota; Lactobacillus; Placental growth factor; Preeclampsia; Pregnant women.

Fig. 1

Effects of PE on the Overall Structure of Gut Microbiota. (A, B) Principal coordinate analysis based on Bray-Curtis distance of the bacterial communities in NW, NP, APG and PE. The differences in beta diversity between each paired groups were tested by permutational multivariate analysis of variance (PERMANOVA, FDR was controlled at 5%). (C, D, E) The Shannon, Chao1 and observed OTUs estimates of fecal microbiota in each group. (F) Venn diagram of the numbers of the identified OTUs. Dots in box plot show values in each individual. An asterisk indicated a significant difference (* at p < .05, ** p < .01) between the labelled groups

Fig. 2

Gut microbiota compositional shifts in APG and PE at phylum and genus level. (A) Relative abundances of phyla in all the four groups. (B) Relative abundances of the phyla TM7 in samples. An asterisk indicated a significant difference (* at p < .05, ** p < .01) between the labelled paired groups. Paired t test followed by FDR correction. (C) Neighbour joining phylogenetic tree of all the 162 annotatable genera. Text indicated the generic name of each bacterial taxa (plot) and the colour of the text and plot represented the level of phylum of each genus. (D) Mean relative abundance of all genera in each group. (E) Normalized abundance of each genus in samples

Fig. 3

Disturbance of gut microbiota was associated with the development of PE. (A) Relative abundances of the most abundant ten genera in samples. (B) linear discriminant analysis effect size identified the most differentially abundant taxa between the selected two groups. The enriched taxa were indicated with a positive LDA score, and taxa enriched in NP have a negative score. Only taxa meeting an LDA significant threshold of > 3 were shown. The asterisk indicated a significant relative abundance change of the taxa (* at p < .05, ** p < .01) between the selected paired groups. Paired t test followed by FDR correction. (C) Correlations between the relative abundance of the selected genus and the clinical parameters

Fig. 4

The loss of g_Lactobacilli is only related to the abnormal clinical indicators of Pre-eclampsia patients. (A) Relative abundances of g_Lactobacilli in samples. (B) The correlations between the relative abundance of g_Lactobacilli and the concentrations of SBP, DBP and UP. (C) The relative abundances of the OTUs belonged to the g_Lactobacilli. (D) The correlations between the relative abundance of OTU255 and the concentrations of DBP