2. Academic Validation
  3. Oral administration of pioglitazone inhibits pulmonary hypertension by regulating the gut microbiome and plasma metabolome in male rats

Oral administration of pioglitazone inhibits pulmonary hypertension by regulating the gut microbiome and plasma metabolome in male rats

  • Physiol Rep. 2025 Jan;13(1):e70174. doi: 10.14814/phy2.70174.
Zizhou Zhang 1 2 3,  Yaru Liang 1,  Shaocong Mo 1 2 3,  Mingming Zhao 2 3,  Yi Li 2 3,  Chenting Zhang 2 3,  Xiaoqian Shan 2 3 4,  Shiyun Liu 2 3 5,  Jing Liao 2 3 6,  Xiaoyun Luo 2 3 7,  Junqi Zhu 2 3,  Chen Wang 2 3,  Qian Jiang 2 3,  Chi Hou 2 3 8,  Wei Hong 9,  Ning Lai 2 3,  Yuqin Chen 2 3,  Lei Xu 4,  Wenju Lu 2 3,  Jian Wang 2 3 7,  Zhongfang Wang 2 3 7,  Kai Yang 1 2 3
Affiliations

Affiliations

  • 1 Department of Laboratory Medicine, The Affiliated Qingyuan Hospital (Qingyuan People's Hospital), Guangzhou Medical University, Qingyuan, Guangdong, China.
  • 2 State Key Laboratory of Respiratory Disease, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.
  • 3 National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou Medical University, Guangzhou, Guangdong, China.
  • 4 Department of Pulmonary and Critical Care Medicine, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China.
  • 5 Department of Pulmonary Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, Institute of Respiratory Diseases of Sun Yat-Sen University, Guangzhou, Guangdong, China.
  • 6 School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, China.
  • 7 Guangzhou National Laboratory, Guangzhou International Bio Island, Guangzhou, Guangdong, China.
  • 8 Department of Neurology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China.
  • 9 GMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, Guangdong, China.
PMID: 39739369 DOI: 10.14814/phy2.70174
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.

Keywords

gut microbiome; peroxisome proliferator‐activated receptor gamma; pioglitazone; plasma metabolome; pulmonary hypertension.

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