Alexandra De Jong

 Introduction. Pre-eclampsia (PE) is a common pregnancy disorder and is defined by hypertension developing at or after 20 weeks’ gestation and is accompanied by one or more of the following: proteinuria, maternal organ dysfunction, or uteroplacental dysfunction.¹ Pre-eclampsia has a maternal mortality of 15% in developing countries and 0-1.8% in developed countries.² Pre-eclampsia negatively affects both mother and baby. Humans have co-evolved with a set of microbiotas that can change the mother’s metabolism to support the fetus’s growth. Any alteration in the composition of maternal microbiota can be involved in the pathogenesis of PE.³ Gut microbiota is also involved in hypertension by breaking down dietary fiber and producing short-chain fatty acids (SCFAs) that affect vascular tone.³ Microbial meta­bolic capability is required to generate the SCFAs that sustain epithelial integrity and regulatory T cell development in the mother.⁴ Development of the immune system in the fetus is driven by maternal microbial molecules.⁴   Methods. DNA was extracted and sequenced from fecal samples, 48 patients with preeclampsia and 48 control patients. The V4 region of the 16S rRNA gene was amplified and PCR was performed.⁵ Pregnant dams were colonized with E. coli HA107. This strain does not persist in the intestine of mice and thus the dams become germ free again before term and deliver germ free pups.⁶ Preeclampsia is associated with decreased fetal thymic volume.⁷ Germ-free pregnant mice were supplemented with acetate in drinking water.⁷   Results. Microbial alpha diversity (richness and diversity) was lower in the PE group.⁵ Fecal microbiota in patients with PE showed a significant reduction in Ruminococcus species.⁵ Ruminococcus species are important in maintaining gut homeostasis via production of SCFAs.⁵ In utero gestation and postnatal nursing by dams that had been colonized during pregnancy were necessary for significant ILC3 (type 3 innate lymphoid cells) induction.⁶ Prenatal ultrasounds showed that in PE, the fetal thymus was 38% smaller compared to normal pregnancies. This difference increased over gestation and size difference was 50% less at birth.⁷ Acetate supplementation in pregnant mice rescued thymic weight and thymus cell composition. This shows that maternal microbiota derived acetate contributes to fetal thymus development. CD4+ T-cell counts were also restored.⁷  Conclusions. PE is associated with gut microbiota dysbiosis. Gut microbiota produce short chain fatty acids which are decreased in PE patients. Fetal thymus development in preeclamptic mothers is impaired and can be rescued with acetate supplementation.

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