Gut Microbiota and Its Metabolites Modulate Pregnancy Outcomes by Regulating Placental Autophagy and Ferroptosis
Xingyu Du, Mabrouk Elsabagh, Fei He, Huisi Wu, Bei Zhang, Kewei Fan, Mengzhi Wang, Hao Zhang
Abstract
During pregnancy, the regulation of autophagy and ferroptosis dynamically supports placental development and fetal health. Both processes-autophagy, clearing damaged organelles to maintain placental function, and ferroptosis, driven by iron-dependent lipid peroxidation-are involved in pathological conditions such as preeclampsia. Emerging evidence suggests that gut microbiota-derived metabolites act as key regulators of this balance, yet their specific roles across different trimesters remain unclear. This review compiles evidence on how gut microbiota metabolites, like short-chain fatty acids and trimethylamine N-oxide, serve as trimester-specific modulators of the autophagy-ferroptosis balance during pregnancy. We explain how these metabolites influence pregnancy outcomes by regulating placental autophagy and ferroptosis. Furthermore, we explore potential diagnostic and therapeutic approaches for pregnancy complications, focusing on metabolite-based biomarkers and interventions that target microbial-metabolic interactions.