Yudan Qiu, Xiaojiang Lyu, Dashuang Zhang, Hong Xu, Xu He, Jiao Chen, Hanmin Liu, Yang Liu, Liang Xie
West China Second University Hospital and Sichuan University. School of Life Sciences of Fudan University and West China Institute of Women and Children’s Health. Affiliated Hospital of North Sichuan Medical College. Affiliated Hospital of Southwest Medical University. Xizang Autonomous Region Child Development Clinical Medical Research Center. Tianfu·Sichuan Provincial Children’s Hospital.
China
Comprehensive Physiology
Compr Physiol 2026; 16:
DOI: 10.1002/cph4.70094
Abstract
Pulmonary arterial hypertension (PAH) is a chronic, severe cardiopulmonary disease characterized by the progressive increase in pulmonary vascular resistance (PVR) because of the proliferation and fibrosis of the pulmonary arterioles. Although the disease originates in the pulmonary vasculature, it ultimately leads to right heart failure and death. PAH is associated with high mortality rates and poor prognosis, with no therapies currently available to reverse pulmonary vascular remodeling, imposing substantial socioeconomic burdens. Growing interest in the gut-lung axis has highlighted the role of gut microbiota and their metabolites in the occurrence and development of PAH. Evidence showed that gut dysbiosis and metabolite imbalances, involving reduced short-chain fatty acids (SCFAs), increased trimethylamine-N-oxide (TMAO), and dysregulated tryptophan metabolism, contributed to pulmonary vascular remodeling. This review systematically compares gut microbiota and metabolites across PAH murine models (including chronic hypoxia, SU5416/hypoxia [SuHx], monocrotaline [MCT], and non-classical models) and patients (adults and children). The analysis aims to identify disease-specific microbial and metabolic signatures. It is also discussed how the microbiota and their metabolites may influence inflammation around the pulmonary vasculature. Furthermore, the potential of probiotic therapy, fecal microbiota transplantation (FMT), and mesenchymal stem cells (MSCs) therapies as novel treatment strategies for PAH is discussed.
Category
Class I. Pulmonary Hypertension Associated with Inflammation
Acquired Patient Factors Associated with Pulmonary Vascular Disease
Review Articles Concerning Pulmonary Vascular Disease
Age Focus: Pediatric Pulmonary Vascular Disease or Adult Pulmonary Vascular Disease
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: No