Altered Gut Microbiome Profile in Patients With Pulmonary Arterial Hypertension

Area of Science:

• Microbiology
• Pulmonary Hypertension Research
• Gastroenterology

Background:

• Pulmonary arterial hypertension (PAH) is traditionally viewed as a pulmonary vasculature disease.
• Limited success in preventing or halting PAH progression necessitates exploring systemic factors.
• Growing evidence links gut microbiome alterations to various chronic diseases.

Purpose of the Study:

• To investigate if patients with PAH exhibit a distinct gut microbiome.
• To determine if the gut microbiome contributes to and can predict PAH.
• To explore potential diagnostic and therapeutic implications of gut microbiome changes in PAH.

Main Methods:

• Shotgun metagenomics was used to compare the fecal microbiome of 18 PAH patients and 13 healthy controls.
• Taxonomic and functional microbial community changes were analyzed.
• A random forest model was developed to predict PAH based on microbiome composition.

Main Results:

• Significant differences in microbial taxonomy and function were observed between PAH patients and controls.
• Increased pathways for arginine, proline, and ornithine synthesis were noted in PAH patients.
• Elevated trimethylamine/trimethylamine N-oxide and purine metabolism-associated bacteria were found in PAH patients, while beneficial butyrate/propionate producers were decreased.
• A random forest model achieved 83% accuracy in predicting PAH from gut microbiome data.
• Virome analysis revealed enrichment of Enterococcal phages and depletion of Lactococcal phages in PAH patients.

Conclusions:

• Patients with PAH possess a unique gut microbiome profile.
• The gut microbiome composition in PAH patients has high predictive potential for the disease.
• These findings suggest a significant, previously unrecognized role for gut bacteria in PAH pathogenesis, opening avenues for novel therapeutic and diagnostic strategies.