Abstract

Background. Pulmonary arterial hypertension (PAH) is a progressive disease affecting the lung vasculature, characterized by sustained vasoconstriction, vascular remodeling and thrombosis. In recent years, altered immune and inflammatory processes are being considered as pathological hallmarks of the disease. In fact, several studies have reported a relationship between gut dysbiosis and cardiovascular diseases. We hypothesized that the development of PAH may be associated to changes in the intestinal bacterial composition.

Methods. Wistar rats were injected with the VEGF receptor antagonist SU5416 (20mg/kg s.c.) and followed for 2 weeks kept in hypoxia (10% O2, PAH) or injected with vehicle and kept in normoxia (controls). Faecal samples were obtained and microbiome composition was determined by 16S rRNA gene sequencing and bioinformatic analysis.

Results. No effect of PAH on the global microbiome was found (a- or ß-diversity). However, PAH-exposed rats showed gut dysbiosis as indicated by a taxonomy-based analysis. Specifically, PAH rats had a three-fold increase in Firmicutes-to-Bacteroidetes ratio. Within the Firmicutes phylum, there were no large changes in the relative abundance of the bacterial families in PAH. Among Bacteroidetes, all families were less abundant in PAH. All acetate- and most butyrate-producing genera were also decreased in PAH. Moreover, acetate was reduced in the serum of PAH rats.

In conclusion, faecal microbiota composition is altered as a result of PAH. This misbalanced bacterial ecosystem might in turn play a pathophysiological role in PAH by altering the immunologic, hormonal and metabolic homeostasis.