Altered Gut Microbiome Profile in Patients with Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is considered a disease of the pulmonary vasculature. Limited progress has been made in preventing or arresting progression of PAH despite extensive efforts. Our previous studies indicated that PAH could be considered a systemic disease since its pathology involves interplay of multiple organs. This, coupled with increasing implication of the gut and its microbiome in chronic diseases, led us to hypothesize that PAH patients exhibit a distinct gut microbiome that contributes to, and predicts, the disease. Fecal microbiome of 18 type 1 PAH patients (mean pulmonary arterial pressure [mPAP] 57.4, standard deviation 16.7 mmHg) and 13 reference subjects (REF) were compared by shotgun metagenomics to evaluate this hypothesis. Significant taxonomic and functional changes in microbial communities in the PAH cohort were observed. Pathways for the synthesis of arginine, proline and ornithine were increased in PAH cohort compared with REF cohort. Additionally, groups of bacterial communities associated with trimethylamine/ trimethylamine N-oxide and purine metabolism, were increased in PAH cohort. In contrast, butyrate-and propionate-producing bacteria such as Coprococcus, Butyrivibrio, Lachnospiraceae, Eubacterium, Akkermansia and Bacteroides were increased in REF cohort. A random forest model predicted PAH from the composition of the gut microbiome with 83% accuracy. Finally, virome analysis showed enrichment of Enterococcal and relative depletion of Lactococcal phages in the PAH cohort. In conclusion, PAH patients exhibit a unique microbiome profile that has high predictive potential for PAH. This highlights previously unknown roles of gut bacteria in this disease and could lead to new therapeutic, diagnostic or management paradigms for PAH.