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

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.

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

“…Two recent studies were also performed to compare GM composition and abundance between PE and HPC groups during late pregnancy [30,31]. However, our results were notably different from those obtained in these previous studies.…”

“…Specifically, Liu et al [30] did not find significant changes in GM diversity or in the abundance of the four predominant microbes at the phylum level in patients with PE. Lv et al [31] found a different GM abundance at the genus level in patients with PE, when compared with our study. These discrepancies may reflect that following consideration: the average BP and protein urine of the PE patients in our study were notably higher than those in the previous two studies, implying that the patients in our study had more severe PE.…”

Immunological Role of the Maternal Uterine Microbiome in Pregnancy: Pregnancies Pathologies and Alterated Microbiota

“…Another study by den Hollander et al found that Helicobacter pylori, as a cause of chronic inflammatory conditions, is associated with an increased risk of PEC (170). Further, Li Juan et al demonstrated that preeclampsia is associated with a disrupted gut microbiota composition compared with that of women who had uncomplicated pregnancies (171). In a recent review of the current knowledge about the possible association between the microbiome and the development of preeclampsia, Dunn et al did a comprehensive literature search and reported that overall, five groups of investigators studied the microbiome of PEC (172).…”

Shifts in gut microbiome and metabolome are associated with risk of recurrent atrial fibrillation

“…Ruminococcus transplantation in germ-free mice enhances interferon-γ, interleukin 17, and interleukin 22 amounts [29]. Dialister was shown to be associated with antepartum preeclampsia samples [30]. Thus, the balanced steady state in the gut is likely broken in AF subjects, especially in those who suffering from recurrence.…”