Distinct Airway Mycobiome Signature in Patients with Pulmonary Hypertension and Subgroups

The association between lung microbiome and pulmonary hypertension (PH) remain unknown. This study aims to define the airway mycobiome signature and its potential correlation with clinical parameters of PH. Overall, 244 patients with PH and 120 healthy controls (CON) were recruited from three independent centers. The PH group was divided into subgroups not using antibiotics or corticosteroids (non-ANT/CORT), and those using ANT, CORT, or ANT + CORT within 1 month, and clinical classification (Groups 1, 3, and 4), World Health Organization functional class (I–IV), and disease severity based on mean pulmonary artery pressure or pulmonary vascular resistance levels for in-depth comparison. Distinct airway mycobiome profiles were observed in PH, CON, and PH subgroups. Linear discriminant analysis effect size analysis showed increased Purpureocillium, Issatchenkia, and Cyberlindnera and decreased Peroneutypa, Simplicillium, and Metarhizium in patients with PH (non-ANT/CORT, ANT, CORT, and ANT + CORT) than in CON. Receiver operating characteristic analysis indicated a strong prediction of the two fungal genera sets in distinguishing PH and its subgroups from CON. The two major fungal phyla, Ascomycota and Basidiomycota, correlated differently with major clinical factors. Increased connections among the top fungal phyla or genera were observed in the PH than in the CON group. Dominant enrichment (Purpureocillium, Issatchenkia, and Cyberlindnera) and diminishment (Peroneutypa, Simplicillium, and Metarhizium) of fungal genera consistently and strongly predicted PH without being influenced by different PH subgroups. This study provides the first description of the unique airway mycobiome signature in PH and among different PH subgroups.