Abstract
BACKGROUND: Gut dysbiosis and gut-derived metabolites have been linked to pulmonary arterial hypertension. However, associations between specific microbes, and corresponding metabolites, with pulmonary arterial hypertension disease severity is limited. METHODS: This was a prospective cohort study of patients with pulmonary arterial hypertension undergoing right heart catheterization, with pulmonary artery blood subject to nuclear magnetic resonance metabolomics, and simultaneous stool sample shotgun metagenomics. Validation of metabolite levels with disease severity was done in an independent cohort of pulmonary arterial hypertension patients with blood samples from right heart catheterization testing. RESULTS: The presence of Lactobacillus species in the gut microbiome of pulmonary arterial hypertension patients was associated with less severe pulmonary hemodynamics and echocardiographic right ventricular dysfunction. Higher threonine levels were associated with more favorable pulmonary hemodynamic characteristics in both prospective and independent validation cohorts of pulmonary arterial hypertension patients. CONCLUSIONS: Detectable Lactobacillus species in the gut microbiome of pulmonary arterial hypertension patients are associated with more favorable pulmonary hemodynamic and right ventricular characteristics. Circulating gut-derived metabolites may also be involved. Further investigation into the relationship between gut microbial Lactobacillus, circulating metabolites, disease severity, and clinical outcomes in pulmonary arterial hypertension may be warranted.