Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences (J.J., Y.Z., Z.Z., Z.T., X.W., C.Z., Q.Z.).
State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine (J.J., Y.Z., Z.Z., Z.T., X.W., C.Z., Q.Z.).
Circ Res. 2022 Sep 2;131(6):492-506. doi: 10.1161/CIRCRESAHA.122.320771. Epub 2022 Aug 11.
Preeclampsia is one of the leading causes of maternal and perinatal morbidity and is characterized by hypertension, inflammation, and placental dysfunction. Gut microbiota plays key roles in inflammation and hypertension. However, its roles and mechanisms in preeclampsia have not been fully elucidated.
16S rRNA gene sequencing and targeted metabolomics were conducted on stool samples from 92 preeclamptic patients and 86 normal late-pregnant women. Then, fecal microbiota transplantation and in vitro and in vivo functional experiments were performed to explore the roles and mechanisms of gut microbiota in preeclampsia development.
We revealed the gut microbiota dysbiosis in preeclamptic patients, including significant reductions in short-chain fatty acid-producing bacteria and short-chain fatty acids. The gut microbiota of preeclamptic patients significantly exacerbated pathologies and symptoms of preeclamptic rats, whereas the gut microbiota of healthy pregnant women had significant protective effects. , propionate, or butyrate significantly alleviated the symptoms of preeclamptic rats. Mechanistically, they significantly promoted autophagy and M2 polarization of macrophages in placental bed, thereby suppressing inflammation. Propionate also significantly promoted trophoblast invasion, thereby improved spiral arterial remodeling. Additionally, we identified a marker set consisting of , , and short-chain fatty acids that could accurately diagnose preeclampsia.
Our study revealed that gut microbiota dysbiosis is an important etiology of preeclampsia. Gut microbiota and their active metabolites have great potential for the treatment and diagnosis of preeclampsia. Our findings enrich the gut-placenta axis theory and contribute to the development of microecological products for preeclampsia.
子痫前期是导致孕产妇和围产儿发病率和死亡率的主要原因之一，其特征为高血压、炎症和胎盘功能障碍。肠道微生物群在炎症和高血压中发挥关键作用。然而，其在子痫前期中的作用和机制尚未完全阐明。
对 92 例子痫前期患者和 86 例正常晚期孕妇的粪便样本进行 16S rRNA 基因测序和靶向代谢组学分析。然后，进行粪便微生物群移植和体外及体内功能实验，以探索肠道微生物群在子痫前期发展中的作用和机制。
我们揭示了子痫前期患者的肠道微生物群失调，包括短链脂肪酸产生菌和短链脂肪酸显著减少。子痫前期患者的肠道微生物群显著加重了子痫前期大鼠的病理和症状，而健康孕妇的肠道微生物群则具有显著的保护作用。通过补充丙酸盐、丁酸盐或丙酸，可显著缓解子痫前期大鼠的症状。机制上，它们可显著促进胎盘床巨噬细胞的自噬和 M2 极化，从而抑制炎症。丙酸盐还可显著促进滋养细胞侵袭，从而改善螺旋动脉重塑。此外，我们确定了一组由 、、和短链脂肪酸组成的标志物，可准确诊断子痫前期。
我们的研究表明，肠道微生物群失调是子痫前期的重要病因。肠道微生物群及其活性代谢物在子痫前期的治疗和诊断方面具有巨大潜力。我们的发现丰富了肠道-胎盘轴理论，有助于开发用于子痫前期的微生态产品。
