Oral administration of pioglitazone inhibits pulmonary hypertension by regulating the gut microbiome and plasma metabolome in male rats
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.
Authors
- Ning Lai
- Wenju Lu (ORCID: https://orcid.org/0000-0002-5035-9287)
- Zhongfang Wang (ORCID: https://orcid.org/0000-0003-3236-5170)
- Chenting Zhang (ORCID: https://orcid.org/0000-0002-7259-8895)
- Shaocong Mo (ORCID: https://orcid.org/0000-0001-8556-1314)
- Kai Yang (ORCID: https://orcid.org/0000-0003-3044-2240)
- Chi Hou (ORCID: https://orcid.org/0000-0002-1505-6918)
- Junqi Zhu (ORCID: https://orcid.org/0000-0002-5247-9805)
- Mingming Zhao (ORCID: https://orcid.org/0000-0001-5513-1305)
- Xiaoqian Shan (ORCID: https://orcid.org/0000-0002-0745-8343)
- Zizhou Zhang
- Shiyun Liu (ORCID: https://orcid.org/0000-0002-4174-6189)
- Jian Wang (ORCID: https://orcid.org/0000-0002-1278-256X)
- Yi Li (ORCID: https://orcid.org/0000-0002-3875-3513)
- Jiang Qian (ORCID: https://orcid.org/0000-0002-0476-3596)
- Wei Hong (ORCID: https://orcid.org/0000-0003-0265-5863)
- Lei Xu (ORCID: https://orcid.org/0000-0002-6642-5584)
- Jing Liao (ORCID: https://orcid.org/0000-0002-1545-7850)
- Yaru Liang (ORCID: https://orcid.org/0000-0001-6601-9407)
- Yuqin Chen (ORCID: https://orcid.org/0000-0002-7011-7250)
- Xiaoyun Luo
- Chen Wang (ORCID: https://orcid.org/0000-0002-2132-0869)
Institutions
- Sun Yat-sen University (CN)
- Southern University of Science and Technology (CN)
- First Affiliated Hospital of Guangzhou Medical University (CN)
- Third Affiliated Hospital of Sun Yat-sen University (CN)
- State Key Laboratory of Respiratory Disease (CN)
- Inner Mongolia Medical University (CN)
- Guangzhou Medical University (CN)
Publication Details
- Journal
- Physiological Reports
- Published
- 2024-12-31
- DOI
- https://doi.org/10.14814/phy2.70174
- Citations
- 4
- Primary Topic
- Gut microbiota and health
- Type
- article
- Field-Weighted Citation Impact
- 0.94
Funders
- National Natural Science Foundation of China