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

作者：Yihang Chen, Zhenzhen Chen, Lirong Liang, Jifeng Li, Liukun Meng, Yuan Wen, Boqia Xie, Xun Zhang, Feng Lin, Yanxiong Jia, Zhou Fu, Pixiong Su, Zhaohui Tong, Jiuchang Zhong, Xiaoyan Liu · 发表于：EBioMedicine · 年份：2025 · DOI：10.1016/j.ebiom.2025.105686 · 被引用次数：13 · 研究领域：Pulmonary Hypertension Research and Treatments、Gut microbiota and health、Chronic Obstructive Pulmonary Disease (COPD) Research

BACKGROUND: Gut microbiota dysbiosis has been implicated in pulmonary arterial hypertension (PAH). However, the exact roles and underlying mechanisms of multi-kingdom gut microbiota, including bacteria, archaea, and fungi, in PAH remain largely unclear. METHODS: The shotgun metagenomics was used to analyse multi-kingdom gut microbial communities in patients with idiopathic PAH (IPAH) and healthy controls. Furthermore, fecal microbiota transplantation (FMT) was performed to transfer gut microbiota from IPAH patients or monocrotaline (MCT)-PAH rats to normal rats and from normal rats to MCT-PAH rats. FINDINGS: Gut microbiota analysis revealed substantial alterations in the bacterial, archaeal, and fungal communities in patients with IPAH compared with healthy controls. Notably, FMT from IPAH patients or MCT-PAH rats induced PAH phenotypes in recipient rats. More intriguingly, FMT from normal rats to MCT-PAH rats significantly ameliorated PAH symptoms; restored gut bacteria, archaea, and fungi composition; and shifted the plasma metabolite profiles of MCT-PAH rats toward those of normal rats. In parallel, RNA-sequencing analysis demonstrated the expression of genes involved in key signalling pathways related to PAH. A panel of multi-kingdom markers exhibited superior diagnostic accuracy compared with single-kingdom panels for IPAH. INTERPRETATION: Our findings established an association between multi-kingdom gut microbiota dysbiosis and PAH, thereby indicating the therapeutic po...