Zhang Zizhou, Liang Yaru, Mo Shaocong, Zhao Mingming, Li Yi, Zhang Chenting, Shan Xiaoqian, Liu Shiyun, Liao Jing, Luo Xiaoyun, Zhu Junqi, Wang Chen, Jiang Qian, Hou Chi, Hong Wei, Lai Ning, Chen Yuqin, Xu Lei, Lu Wenju, Wang Jian, Wang Zhongfang, Yang Kai
Department of Laboratory Medicine, The Affiliated Qingyuan Hospital (Qingyuan People's Hospital), Guangzhou Medical University, Qingyuan, Guangdong, China.
State Key Laboratory of Respiratory Disease, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.
Physiol Rep. 2025 Jan;13(1):e70174. doi: 10.14814/phy2.70174.
The oral administrated thiazolidinediones (TZDs) have been widely reported to alleviate experimental pulmonary hypertension (PH). However, previous studies mainly focused on their beneficial effects on the cardiopulmonary vascular system but failed to determine their potential roles on gut microenvironment. This study aims to investigate the effects of pioglitazone, an oral TZD drug, on gut microbiome in classic PH rat models induced by hypoxia (HPH) or SU5416/hypoxia (SuHx-PH) and evaluate the therapeutic potential of supplementation of selective probiotics for experimental PH. Pioglitazone remarkably inhibited the PH pathogenesis in both models and reshaped the gut microbiome and plasma metabolome. Correlation analyses represented strong and unique association between the protective metabolites and bacteria genera (Roseburia, Lactobacillus, and Streptococcus) that were positively stimulated by pioglitazone. Supplementation of selective probiotics Roseburia intestinalis (R. intestinalis) partially attenuated SuHx-PH and rebuilt a novel gut microbiome and host metabolome. This study reports for the first time that oral administration of pioglitazone protects PH by regulating the gut microbiome and host metabolome, providing novel insights for the TZD drugs. The data also supports that modulation of gut microbiota by supplementation of selective probiotics could be a novel effective therapeutic strategy for the treatment of PH.
口服噻唑烷二酮类药物（TZDs）已被广泛报道可缓解实验性肺动脉高压（PH）。然而，以往的研究主要集中在它们对心肺血管系统的有益作用上，却未能确定它们在肠道微环境中的潜在作用。本研究旨在探讨口服TZDs药物吡格列酮对缺氧（HPH）或SU5416/缺氧（SuHx-PH）诱导的经典PH大鼠模型肠道微生物群的影响，并评估补充选择性益生菌对实验性PH的治疗潜力。吡格列酮在两种模型中均显著抑制PH发病机制，并重塑肠道微生物群和血浆代谢组。相关性分析表明，吡格列酮正向刺激的保护性代谢物与细菌属（罗氏菌属、乳杆菌属和链球菌属）之间存在强烈且独特的关联。补充选择性益生菌肠道罗氏菌（R. intestinalis）可部分减轻SuHx-PH，并重建新的肠道微生物群和宿主代谢组。本研究首次报道口服吡格列酮通过调节肠道微生物群和宿主代谢组来保护PH，为TZDs药物提供了新的见解。数据还支持通过补充选择性益生菌来调节肠道微生物群可能是治疗PH的一种新型有效治疗策略。
