Detectable Lactobacillus species in the gut microbiome of pulmonary arterial hypertension patients are associated with more favorable pulmonary hemodynamic and right ventricular characteristics, and higher threonine levels were associated with more favorable pulmonary hemodynamic characteristics in both prospective and independent validation cohorts.
Key Findings
Results
The presence of Lactobacillus species in the gut microbiome was associated with less severe pulmonary hemodynamics in PAH patients.
This was a prospective cohort study using simultaneous stool sample shotgun metagenomics and pulmonary artery blood metabolomics collected at the time of right heart catheterization.
Patients with detectable Lactobacillus species showed more favorable pulmonary hemodynamic characteristics compared to those without detectable Lactobacillus.
The association between Lactobacillus presence and hemodynamics was identified through shotgun metagenomics of stool samples paired with nuclear magnetic resonance metabolomics of pulmonary artery blood.
Right heart catheterization-derived hemodynamic parameters were used as the primary measure of disease severity.
Results
The presence of Lactobacillus species was associated with less severe echocardiographic right ventricular dysfunction in PAH patients.
Echocardiographic assessment of right ventricular function was used as a secondary measure of disease severity alongside hemodynamic parameters.
Patients with detectable Lactobacillus in the gut microbiome demonstrated more favorable right ventricular characteristics on echocardiography.
Both pulmonary hemodynamic and echocardiographic findings were assessed concurrently in the prospective cohort.
Results
Higher circulating threonine levels were associated with more favorable pulmonary hemodynamic characteristics in PAH patients.
Threonine levels were measured via nuclear magnetic resonance metabolomics of pulmonary artery blood samples.
The association between higher threonine and more favorable hemodynamics was identified in the primary prospective cohort.
This finding was validated in an independent cohort of PAH patients with blood samples from right heart catheterization testing.
Threonine is a gut-derived metabolite, suggesting a potential mechanistic link between gut microbiome composition and circulating metabolites in PAH.
Background
Gut dysbiosis and gut-derived metabolites have been previously linked to pulmonary arterial hypertension, but associations between specific microbes and metabolites with PAH disease severity were previously limited.
Prior literature established a general link between gut dysbiosis and PAH but lacked specificity regarding which microorganisms or metabolites are implicated.
This study was designed to address the gap in knowledge regarding specific microbial species and their corresponding metabolites in relation to PAH disease severity.
The study used a prospective cohort design with simultaneous sampling of gut microbiome and circulating metabolites at the time of right heart catheterization.
Methods
A prospective cohort study design was used with simultaneous shotgun metagenomics and nuclear magnetic resonance metabolomics performed at the time of right heart catheterization.
Stool samples were subjected to shotgun metagenomics to characterize the gut microbiome.
Pulmonary artery blood was analyzed by nuclear magnetic resonance metabolomics to characterize circulating metabolites.
Both sampling modalities were performed simultaneously at the time of clinically indicated right heart catheterization in PAH patients.
An independent validation cohort of PAH patients with blood samples from right heart catheterization was used to validate metabolite findings.
What This Means
This research suggests that specific bacteria living in the gut may be linked to how severe pulmonary arterial hypertension (PAH) is in patients. PAH is a serious condition where the blood pressure in the arteries supplying the lungs becomes abnormally high, putting strain on the right side of the heart. The researchers collected stool samples and blood from the pulmonary artery at the same time as patients underwent a standard diagnostic procedure called right heart catheterization, allowing them to directly connect gut bacteria and blood chemistry to measures of disease severity.
The study found that patients with PAH who had detectable Lactobacillus bacteria in their gut tended to have less severe disease — both in terms of the pressures measured in their pulmonary arteries and in how well their right ventricle (the heart chamber that pumps blood to the lungs) was functioning on echocardiography. Additionally, higher blood levels of threonine, an amino acid that can be produced or influenced by gut bacteria, were associated with more favorable lung blood pressure measurements, and this finding held up when tested in a separate group of PAH patients.
This research suggests that the community of microbes living in the gut may play a role in PAH disease severity, potentially through the production of circulating molecules like threonine. While the study cannot establish that Lactobacillus or threonine directly cause better outcomes — only that they are associated — the findings open the door to future research exploring whether interventions targeting the gut microbiome could someday be relevant to PAH management.
Jose A, Apewokin S, Ollberding N, Duan Q, Trannguyen J, Prisco S, et al.. (2026). Lactobacillus Is Associated With Disease in Pulmonary Arterial Hypertension: A Prospective Cohort Study.. Comprehensive Physiology. https://doi.org/10.1002/cph4.70161