菌群代谢物介导滋养细胞代谢重编程 参与子痫前期

Gut Microbiota Metabolites Mediate Trophoblast Metabolic Reprogramming in Preeclampsia

摘要: 子痫前期是妊娠期高发且严重威胁母婴安全的并发症，胎盘滋养细胞功能异常与代谢紊乱是其核心病理环节。近年来，肠道菌群及其代谢产物在妊娠相关疾病中的调控作用成为研究热点，肠–胎盘轴机制为阐释子痫前期发病机理提供了全新视角。肠道菌群失调可引发短链脂肪酸、胆汁酸、色氨酸代谢物及三甲胺-N-氧化物等代谢物谱异常，通过能量代谢调控、表观遗传修饰、免疫微环境重塑等通路，诱导胎盘滋养细胞发生代谢重编程，抑制滋养细胞侵袭与螺旋动脉重塑，加剧胎盘氧化应激与炎症反应，最终推动子痫前期发生发展。本文系统梳理肠道菌群代谢物的种类与功能、滋养细胞代谢异常特征，阐明菌群代谢物介导滋养细胞代谢重编程的分子通路，总结临床生物标志物开发与微生态干预的研究进展，展望精准防治策略，为子痫前期的早期预警与靶向治疗提供理论依据与新思路。

Abstract: Preeclampsia is a highly prevalent and life-threatening complication of pregnancy, with placental trophoblast dysfunction and metabolic disorders serving as its core pathological link. In recent years, the regulatory role of the gut microbiota and its metabolites in pregnancy-related diseases has become a research hotspot, and the “gut-placenta axis” mechanism provides a novel perspective for elucidating the pathogenesis of preeclampsia. Gut microbiota dysbiosis leads to abnormal profiles of metabolites such as short-chain fatty acids (SCFAs), bile acids, tryptophan metabolites, and trimethylamine-N-oxide (TMAO). These metabolites induce metabolic reprogramming in placental trophoblasts through pathways including energy metabolism regulation, epigenetic modification, and immune microenvironment remodeling. Such reprogramming inhibits trophoblast invasion and spiral artery remodeling, exacerbates placental oxidative stress and inflammatory responses, and ultimately promotes the development of preeclampsia. This paper systematically reviews the types and functions of gut microbiota metabolites, the characteristics of trophoblast metabolic abnormalities, clarifies the molecular pathways of microbiota metabolites mediating trophoblast metabolic reprogramming, summarizes research advances in clinical biomarker development and microecological interventions, and prospects precise prevention and treatment strategies. It provides theoretical basis and new ideas for early warning and targeted therapy of preeclampsia.