Altered gut microbiota in chronic thromboembolic pulmonary hypertension

Background: The pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH) is associated with inflammation as withother types of pulmonary hypertension. Recently, the involvement of altered gut microbiota has been reported in patients with pulmonary arterial hypertension (PAH) (Kim S, et al. Hypertension 2020: 75: 1063-1071) and a SU5416/hypoxia-induced PAH animal model (Sanada TJ, et al. Pulm Circ 2020: 10: 2045894020929147). The aim of this study was to characterise the gut microbiota in CTEPH patients and assess the relationship between the pathogenesis of CTEPH and gut microbiota. Methods: Faecal samples were collected from 11 CTEPH patients at diagnosis, and components of gut microbiota were assessed using 16S rRNA gene sequencing. Control data were collected from the database of the National Institutes of Biomedical Innovation, Health, and Nutrition and were compared with those of CTEPH patients. The age, sex, and body mass index were matched between CTEPH patients and healthy control. Results: The principal coordinate analysis revealed the difference in components of the gut microbiota between CTEPH patients and controls. Compared to healthy controls, in CTEPH patients, the bacterial alpha diversity was lower (p<0.05), some butylate-producing bacteria were significantly reduced (p<0.05), and serum concentration of endotoxin was significantly higher (p<0.001). A gram-negative bacteria (Bacteria X) composition in CTEPH patients was correlated with pulmonary arterial resistance (p<0.05). Conclusion: The gut microbiota composition of CTEPH patients and healthy controls was different. This alteration might be associated with inflammation and the pathogenesis of CTEPH.