Prevotella histicola suppresses ferroptosis to mitigate ethanol-induced gastric mucosal lesion in mice

作者：Sisi Wang, Du Wu, Fangquan Wu, Hongxia Sun, Xinyu Wang, Hongbing Meng, Qingqing Lin, Keke Jin, Fangyan Wang · 发表于：Research Square · 年份：2022 · DOI：10.21203/rs.3.rs-2181800/v1 · 研究领域：Ferroptosis and cancer prognosis、Inflammatory mediators and NSAID effects、Cancer, Lipids, and Metabolism

Abstract Background : Ethanol-inducedgastric mucosal lesion (EGML) is one of the most common digestivedisorderswith the limited outcomes of current therapies in clinic. P. histicola was shown probiotic efficacy against arthritis, multiple sclerosis and estrogen deficiency-induced depression in mice, but the role of P. histicola in ethanol-induced gastric mucosal lesion remains unclear despite of its high colonization in stomach. Ferroptosis characterized by lipids peroxidation may be involved in EGML. Herein, we aimed to investigate the effects and underlying mechanism of P. histicola on EGML in the ferroptosis dependent pathway. Methods: P. histicola was intragastrically treated for a week and deferoxamine (DFO), a ferroptosis inhibitor, was intraperitoneally injected prior to oral ethanol administration, respectively. The gastric mucosal lesion and ferroptosis were assessed by pathological examination, quantitative real-time PCR, Western blot and immunofluorescence. Results: P. histicola was originally found to attenuate EGML by the reduced pathological changes and ROS accumulation. The proferroptotic genes of Transferrin Receptor (TFR1), Solute Carrier Family 39 Member 14 (SLC39A14), Heme Oxygenase-1 (HMOX-1), Acyl-CoA Synthetase Long-chain Family Member 4 (ACSL4), Cyclooxygenase 2 (COX-2) and mitochondrial Voltage-dependent Anion Channels (VDACs) were upregulated, but the anti-ferroptotic System Xc-/ Glutathione Peroxidase 4 (GPX4)axis was reduced after ethanol administra...