BACKGROUND AND OBJECTIVE: Pulmonary hypertension (PH) is a progressive pulmonary vascular disease, characterized by persistent pulmonary vasoconstriction, pulmonary vascular remodeling and thrombosis in situ. This vascular pathological change is considered to be a key factor in the development of PH. In recent years, experimental studies have found that microecology is closely related to vascular diseases. At the same time, it has been found that the changes of airway microbial flora are related to systemic inflammatory response in patients with lung cancer, acute respiratory distress syndrome, sepsis and chronic airway diseases, and the latter is also an important reason for the progression of pulmonary hypertension. However, the composition and distribution of airway microecology in pulmonary hypertension are not fully understood at present. In this study, metagenomic sequencing was used to investigate the composition characteristics and changes of airway microecology in patients with pulmonary hypertension compared with healthy people. Methods: 118 patients with pulmonary hypertension diagnosed by right cardiac catheter and 79 healthy controls were included in this study. Throat swab samples were collected from all subjects and microorganism 16SrRNA gene sequencing was performed, and the sequencing results were analyzed for bioinformation statistics. Results: The alpha diversity analysis of the flora showed that the Ace index of the PH group (P<0.01), Sobs index (P<0.001) and the Simpson index (P<0.05) compared with the healthy control group, indicating that the richness of bacterial flora in the airway of patients with pulmonary hypertension increased, but the diversity of bacteria decreased. Beta diversity analysis revealed a marked difference in bacterial community structure between the two groups. At the same time, this paper compares the two groups from phylum to genus of different taxonomic levels. At the phylum level, the proportion of Firmicutes increased in the PH group (P<0.05), the proportion of bacilloids and saccharifying bacteria decreased (bothP<0.05)； At the family level, the PH group Streptococcus family (P<0.01), Ciliaceae (P<0.05) increased proportion; Porphyromonasaceae (P<0.05) and Flavobacteriaceae (P<0.01) is lower in proportion; At the genus level, PH group streptococci (P<0.01) and Pilobacteria (P<0.05) significantly increased, while granulobacteria (P<0.05) and Proteobacter (P<0.05) was significantly lower than that of the control group. Linear discriminant analysis revealed that the proportions of Streptococcus, Lauteropia and Ralderia vermiculata were significantly higher in patients with PH than in healthy controls. Random forest models were established based on these 3 genera, and ROC analysis assessed the area under the curve to be 0.73 (95%CI：0.67~0.80）。 Further functional predictive analysis suggested that the enrichment of airway flora in patients with pulmonary arterial hypertension was closely related to the invasion of epithelial cells by bacteria and the activation of endotoxin and other signaling pathways. CONCLUSIONS: The results of this study show differences in the composition of airway microecology in patients with PH compared to healthy people. Streptococcus spp., Lauteropia spp., and Relleria vermiculata can be used as potential predictors to distinguish between patients with PH and healthy people, providing novel, non-invasive diagnostic biomarkers for early clinical diagnosis of PH.
