High-fibre diet affects gut microbiome and prevents the development of hypoxia-induced pulmonary hypertension

Pulmonary hypertension due to chronic lung diseases, including chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis, is one of the major causes of death worldwide. This pathology is characterised by structural changes in the pulmonary vasculature and sustained vasoconstriction. Treatment options for pulmonary hypertension are based on the regulation of vascular tone but does not demonstrate high efficacy and new ways for controlling disease are needed. Little is known about the role of the gut microbiota and their metabolites in the development of pulmonary hypertension. Recent studies demonstrated that systemic hypertension can be attenuated by gut microbiota intervention. Gut microbes can promote the development of systemic hypertension and can also be a therapeutic target to reduce blood pressure. The aim of this study was to determine if modification of the gut microbiome using a diet that is rich in soluble fibre could prevent the development of hypoxia-induced pulmonary hypertension. The high-fibre diet decreased adverse pulmonary vascular remodelling and decreased right ventricular systolic pressure in mice exposed to hypoxia. These changes were associated with increased abundance of short chain fatty acid-producing bacteria in the gut. Further analysis showed that soluble fibre consumption affected lung myeloid cell populations that were previously recognised as important players in the pathogenesis of pulmonary hypertension. Untargeted proteomic analysis of the right ventricle and the lungs revealed potential molecular pathways that may be affected by soluble fibre supplementation. In the right ventricle these pathways were associated with cardiac hypertrophic changes and glucose metabolism. Diet-induced alterations in inflammatory pathways and pathways related to vessel remodelling were found in the lungs of experimental mice. These data demonstrate for the first time that a high-fibre diet can act on the gut microbiome in the mouse model of hypoxia-induced pulmonary hypertension and prevent disease progression. Soluble fibre can significantly supress structural vascular remodelling and affect pulmonary immune system similar to previous published studies that were obtained in models mimicking left ventricular and systemic circulation dysfunction. Supplementation with high fibre diet could be considered as a supportive lifestyle modification for patients with pulmonary hypertension or subjects that have a high risk of pulmonary diseases.2022-12-07 JG: Author's signature removed from PD