Antibiotic-driven and microbiota-targeted therapy for advanced management of pulmonary hypertension

Pulmonary hypertension (PH), particularly secondary to hypoxic lung diseases like chronic obstructive pulmonary disease (COPD), lacks effective targeted therapies. Emerging evidence suggests that microbiota imbalances contribute to PH progression, raising the possibility of microbiome-targeted interventions. This study explores the role of antibiotics in modulating microbiota and ameliorating PH.

A retrospective cohort analysis was conducted using the Medical Information Mart for Intensive Care (MIMIC) database to assess changes in mean pulmonary artery pressure (mPAP) after antibiotic treatment. Subsequently, clinical data of 220 PH patients (including group 1, 3, and 4 PH) from single clinical center were analyzed, with 16S rRNA sequencing performed on pharyngeal and fecal samples to evaluate microbiota composition. A hypoxia-induced PH rat model was used to investigate the effects of antibiotic treatment on hemodynamics, pulmonary vascular remodeling, and gut microbiota.

Antibiotic use was associated with reduced mPAP in PH patients, particularly in hypoxic associated PH. Microbiota diversity decreased with antibiotic treatment, but probiotic species like Lactobacillus were enriched. In hypoxia-induced PH rats, antibiotics attenuated right ventricular systolic pressure (RVSP), reduced pulmonary vascular thickening, and preserved gut villi integrity. Lactobacillus and Anaerostipes correlated negatively with PH severity, suggesting a protective role.

Antibiotic-driven microbiota modulation may alleviate PH progression by targeting dysbiosis and reducing inflammation. These findings support further investigation into optimized antibiotic regimens as a therapeutic strategy for PH, particularly in hypoxic lung disease-associated cases.