Virtual symposium by the iPVD Consortium: Microbes series – microbiome & microbial metabolites

Date: February 28, 2024

Microbiome and Pulmonary Circulation: Where are we going? (moderator introduction)
Dr. Suellen D. Oliviera (University of Illinois at Chicago, USA)

Pro-inflammatory Gut Microbiome in PAH Patients
Dr. Thenappan Thenappan (University of Minnesota, USA)

Insights into the Role of Microbiome Metabolites in PH
Dr. Imad Al Ghouleh (University of Pittsburgh, USA)

 

Summary:

  • The role of the microbiome in human health and disease has become clearer through projects like the Human Microbiome Project, revealing that organs previously thought to be sterile (e.g., lungs) actually have distinct microbiotas. The lungs harbor microbiota similar to those in the gut, raising new questions about inter-organ microbial interactions.
  • Pulmonary arterial hypertension (PAH) patients exhibit a pro-inflammatory gut microbiome linked to systemic and vascular inflammation.
  • Gut dysbiosis contributes to chronic systemic inflammation via two main mechanisms: 1) increased gut permeability releasing bacterial endotoxins (LPS) followed by immune activation, and 2) production of pro-inflammatory or anti-inflammatory microbial metabolites.
  • The gut microbiome produces metabolites like pro-inflammatory trimethylamine N-oxide (TMAO) and anti-inflammatory short-chain fatty acids (SCFAs) such as butyrate. PAH patients have reduced gut microbiome diversity along with an altered composition enriched with pro-inflammatory bacteria (e.g., Bacteroidetes, Proteobacteria) and diminished beneficial bacteria (e.g., Faecalibacterium prausnitzii). Gut microbiome alterations correlate strongly with pulmonary vascular disease severity, and lower gut diversity is associated with worse clinical outcomes in PAH patients.
  • Butyrate inhibits endothelial dysfunction and endothelial-to-mesenchymal transition (EndoMT), which contributes to vascular remodeling in PH. Animal studies show butyrate reduces hypoxia-induced PH symptoms, including right ventricular pressure and inflammation.
  • EBP50, a scaffolding protein important for endothelial function, is decreased in PH and restored by butyrate treatment. Reduced EBP50 negates these benefits in animal models. Hypoxia and EBP50 levels both affect gut microbiome diversity, indicating complex host-microbiome interactions in PH.