Multi-kingdom gut microbiota dysbiosis is associated with the development of pulmonary arterial hypertension

Gut microbiota dysbiosis has been implicated in pulmonary arterial hypertension (PAH). However, most studies have focused on the bacterial community and the exact role and mechanisms of multi-kingdom gut microbiota, including bacteria, archaea and fungi in PAH remains largely unclear. Idiopathic PAH (IPAH) patients exhibited distinct gut microbiota profiles with altered bacterial, archaeal and fungal compositions compared to healthy controls. Fecal microbiota transplantation (FMT) from IPAH patients or monocrotaline (MCT)-induced PAH rats to antibiotic treated rats induced PAH phenotypes, including increased right ventricular systolic pressure (RVSP) and pulmonary vascular remodeling. Conversely, FMT from normal rats to MCT-PAH rats ameliorated PAH symptoms and reversed multi-kingdom gut microbiota dysbiosis. Metabolomics revealed significant alterations in plasma metabolites. Our findings established a causal link between multi-kingdom gut microbiota dysbiosis and PAH, demonstrating the therapeutic potential of FMT in reversing PAH phenotypes. More importantly, in addition to gut bacteria, gut archaeal and fungal communities also significantly correlate with PAH pathogenesis, highlighting their indispensable role in the gut.