Preeclampsia is a progressive hypertensive disorder of pregnancy affecting 2-8% of pregnancies globally. Preexisting chronic hypertension is a major risk factor associated with developing preeclampsia, and growing evidence suggests a role for the gut microbiome in the development of preeclampsia. However, neither alterations in the gut microbiome associated with preeclampsia nor the mechanisms involved are fully understood. In this study, we tested the hypothesis that normal gestational maternal gut microbiome remodeling is impaired in the Dahl salt-sensitive (Dahl S) rat model of superimposed preeclampsia. Gut microbiome profiles of pregnant Dahl S, normal pregnant Sprague Dawley (SD) and matched virgin controls were assessed by 16S rRNA gene sequencing at baseline; during early, middle and late pregnancy; and one-week postpartum. Dahl S rats had significantly higher abundance in Proteobacteria, and multiple genera were significantly different from SD rats at baseline. The pregnant SD displayed a significant increase in Proteobacteria and genera such as Helicobacter, but these were not different between pregnant and virgin Dahl S rats. By late pregnancy, Dahl S rats had significantly lower a-diversity and Firmicutes compared to their virgin Dahl S controls. β-diversity was significantly different among groups (p<0.001). KEGG metabolic pathways including those associated with short-chain fatty acids were different in Dahl S pregnancy but not in SD pregnancy. These results reveal an association between chronic hypertension and gut microbiome dysbiosis which may hinder pregnancy-specific remodeling in the gut microbial composition during superimposed preeclampsia.

中文翻译：

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叠加慢性高血压的先兆子痫大鼠模型中妊娠期肠道微生物重塑受损

先兆子痫是一种进行性妊娠期高血压疾病，影响全球 2-8% 的妊娠。先前存在的慢性高血压是与先兆子痫发展相关的主要危险因素，越来越多的证据表明肠道微生物组在先兆子痫的发展中发挥作用。然而，与先兆子痫相关的肠道微生物组的改变和所涉及的机制都没有被完全理解。在这项研究中，我们检验了在叠加先兆子痫的达尔盐敏感性 (Dahl S) 大鼠模型中，正常妊娠母体肠道微生物组重塑受损的假设。通过基线 16S rRNA 基因测序评估怀孕 Dahl S、正常怀孕 Sprague Dawley (SD) 和匹配的原始对照的肠道微生物组谱；在妊娠早期、中期和晚期；和产后一周。Dahl S 大鼠在 Proteobacteria 中的丰度显着更高，并且多个属在基线时与 SD 大鼠显着不同。怀孕的 SD 表现出变形菌和螺杆菌属的显着增加，但这些在怀孕和处女 Dahl S 大鼠之间没有差异。到怀孕后期，与处女 Dahl S 对照相比，Dahl S 大鼠的 a 多样性和厚壁菌门显着降低。β-多样性在各组之间存在显着差异（p<0.001）。包括与短链脂肪酸相关的 KEGG 代谢途径在 Dahl S 妊娠中不同，但在 SD 妊娠中则不同。这些结果揭示了慢性高血压与肠道微生物群失调之间的关联，这可能会阻碍叠加先兆子痫期间肠道微生物组成的妊娠特异性重塑。