Gut dysbiosis in patients with pulmonary arterial hypertension (PAH) can lead to a proinflammatory environment, according to a study published in the American Journal of Respiratory and Critical Care Medicine. 

Studies indicate that a key driver of pulmonary vascular remodeling in PAH is perivascular inflammation. The exact mechanisms driving this process remain unclear. 

Scientists have proposed that an altered gut microbiome (otherwise known as gut dysbiosis) can trigger systemic inflammation. They believe that the inability of the gut microbiota to produce anti-inflammatory metabolites weakens the gut barrier. In addition, altered composition of products such as secondary bile acids and trimethylamine can lead to systemic immune dysregulation. 


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The role of gut microbiota in disease outcomes in PAH has not been fully elucidated. The authors of the study sought to characterize the gut microbiome in patients with PAH and uncover any associations with immune dysregulation.

Read more about PAH etiology  

The research team studied patients with PAH seen at the University of Minnesota Pulmonary Hypertension program between February 2019 and March 2021. PAH secondary to heart, lung, and thromboembolic disease were excluded. For selected PAH participants, stool samples were collected and plasma analysis was performed. Researchers also performed tests to study gut permeability, inflammation, and microbial metabolites in patients with PAH. 

The researchers discovered that patients with PAH had significantly reduced bacterial diversity compared with healthy controls. In addition, patients with PAH demonstrated a distinct gut microbiome signature at the phylogenetic level. They also discovered that gut dysbiosis is associated with the severity of pulmonary vascular disease in patients with PAH. Patients with PAH also had lower copies of a number of gut microbial genes encoding the synthesis of anti-inflammatory metabolites. 

“Despite recent advances in determining PAH pathogenesis, diagnosis, and treatment, our findings provide a compelling rationale to investigate strategies such as microbiota transplant therapy to target the gut microbiome to treat PAH,” the authors wrote. 

Reference

Moutsoglou DM, Tatah J, Prisco SZ, et al. Pulmonary arterial hypertension patients have a proinflammatory gut microbiome and altered circulating microbial metabolitesAm J Respir Crit Care Med. 2022;10.1164/rccm.202203-0490OC. doi:10.1164/rccm.202203-0490OC