Oral administration of pioglitazone inhibits pulmonary hypertension by regulating the gut microbiome and plasma metabolome in male rats
Abstract 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...
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| Format: | Article |
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Wiley
2025-01-01
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| Series: | Physiological Reports |
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| Online Access: | https://doi.org/10.14814/phy2.70174 |
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| author | Zizhou Zhang Yaru Liang Shaocong Mo Mingming Zhao Yi Li Chenting Zhang Xiaoqian Shan Shiyun Liu Jing Liao Xiaoyun Luo Junqi Zhu Chen Wang Qian Jiang Chi Hou Wei Hong Ning Lai Yuqin Chen Lei Xu Wenju Lu Jian Wang Zhongfang Wang Kai Yang |
| author_facet | Zizhou Zhang Yaru Liang Shaocong Mo Mingming Zhao Yi Li Chenting Zhang Xiaoqian Shan Shiyun Liu Jing Liao Xiaoyun Luo Junqi Zhu Chen Wang Qian Jiang Chi Hou Wei Hong Ning Lai Yuqin Chen Lei Xu Wenju Lu Jian Wang Zhongfang Wang Kai Yang |
| author_sort | Zizhou Zhang |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-240565b2943c406fad011e21826523f3 |
| institution | Kabale University |
| issn | 2051-817X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Physiological Reports |
| spelling | doaj-art-240565b2943c406fad011e21826523f32025-01-15T13:36:31ZengWileyPhysiological Reports2051-817X2025-01-01131n/an/a10.14814/phy2.70174Oral administration of pioglitazone inhibits pulmonary hypertension by regulating the gut microbiome and plasma metabolome in male ratsZizhou Zhang0Yaru Liang1Shaocong Mo2Mingming Zhao3Yi Li4Chenting Zhang5Xiaoqian Shan6Shiyun Liu7Jing Liao8Xiaoyun Luo9Junqi Zhu10Chen Wang11Qian Jiang12Chi Hou13Wei Hong14Ning Lai15Yuqin Chen16Lei Xu17Wenju Lu18Jian Wang19Zhongfang Wang20Kai Yang21Department of Laboratory Medicine The Affiliated Qingyuan Hospital (Qingyuan People's Hospital), Guangzhou Medical University Qingyuan Guangdong ChinaDepartment of Laboratory Medicine The Affiliated Qingyuan Hospital (Qingyuan People's Hospital), Guangzhou Medical University Qingyuan Guangdong ChinaDepartment of Laboratory Medicine The Affiliated Qingyuan Hospital (Qingyuan People's Hospital), Guangzhou Medical University Qingyuan Guangdong ChinaState Key Laboratory of Respiratory Disease, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital Guangzhou Medical University Guangzhou Guangdong ChinaState Key Laboratory of Respiratory Disease, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital Guangzhou Medical University Guangzhou Guangdong ChinaState Key Laboratory of Respiratory Disease, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital Guangzhou Medical University Guangzhou Guangdong ChinaState Key Laboratory of Respiratory Disease, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital Guangzhou Medical University Guangzhou Guangdong ChinaState Key Laboratory of Respiratory Disease, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital Guangzhou Medical University Guangzhou Guangdong ChinaState Key Laboratory of Respiratory Disease, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital Guangzhou Medical University Guangzhou Guangdong ChinaState Key Laboratory of Respiratory Disease, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital Guangzhou Medical University Guangzhou Guangdong ChinaState Key Laboratory of Respiratory Disease, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital Guangzhou Medical University Guangzhou Guangdong ChinaState Key Laboratory of Respiratory Disease, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital Guangzhou Medical University Guangzhou Guangdong ChinaState Key Laboratory of Respiratory Disease, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital Guangzhou Medical University Guangzhou Guangdong ChinaState Key Laboratory of Respiratory Disease, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital Guangzhou Medical University Guangzhou Guangdong ChinaGMU‐GIBH Joint School of Life Sciences Guangzhou Medical University Guangzhou Guangdong ChinaState Key Laboratory of Respiratory Disease, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital Guangzhou Medical University Guangzhou Guangdong ChinaState Key Laboratory of Respiratory Disease, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital Guangzhou Medical University Guangzhou Guangdong ChinaDepartment of Pulmonary and Critical Care Medicine The Affiliated Hospital of Inner Mongolia Medical University Hohhot ChinaState Key Laboratory of Respiratory Disease, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital Guangzhou Medical University Guangzhou Guangdong ChinaState Key Laboratory of Respiratory Disease, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital Guangzhou Medical University Guangzhou Guangdong ChinaState Key Laboratory of Respiratory Disease, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital Guangzhou Medical University Guangzhou Guangdong ChinaDepartment of Laboratory Medicine The Affiliated Qingyuan Hospital (Qingyuan People's Hospital), Guangzhou Medical University Qingyuan Guangdong ChinaAbstract 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.https://doi.org/10.14814/phy2.70174gut microbiomeperoxisome proliferator‐activated receptor gammapioglitazoneplasma metabolomepulmonary hypertension |
| spellingShingle | Zizhou Zhang Yaru Liang Shaocong Mo Mingming Zhao Yi Li Chenting Zhang Xiaoqian Shan Shiyun Liu Jing Liao Xiaoyun Luo Junqi Zhu Chen Wang Qian Jiang Chi Hou Wei Hong Ning Lai Yuqin Chen Lei Xu Wenju Lu Jian Wang Zhongfang Wang Kai Yang Oral administration of pioglitazone inhibits pulmonary hypertension by regulating the gut microbiome and plasma metabolome in male rats Physiological Reports gut microbiome peroxisome proliferator‐activated receptor gamma pioglitazone plasma metabolome pulmonary hypertension |
| title | Oral administration of pioglitazone inhibits pulmonary hypertension by regulating the gut microbiome and plasma metabolome in male rats |
| title_full | Oral administration of pioglitazone inhibits pulmonary hypertension by regulating the gut microbiome and plasma metabolome in male rats |
| title_fullStr | Oral administration of pioglitazone inhibits pulmonary hypertension by regulating the gut microbiome and plasma metabolome in male rats |
| title_full_unstemmed | Oral administration of pioglitazone inhibits pulmonary hypertension by regulating the gut microbiome and plasma metabolome in male rats |
| title_short | Oral administration of pioglitazone inhibits pulmonary hypertension by regulating the gut microbiome and plasma metabolome in male rats |
| title_sort | oral administration of pioglitazone inhibits pulmonary hypertension by regulating the gut microbiome and plasma metabolome in male rats |
| topic | gut microbiome peroxisome proliferator‐activated receptor gamma pioglitazone plasma metabolome pulmonary hypertension |
| url | https://doi.org/10.14814/phy2.70174 |
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