Dysregulated tryptophan metabolism and gut microbiota in chronic hypoxia-induced pulmonary hypertension rats

Pulmonary hypertension (PH) is a life-threatening disease, mainly caused by pulmonary arterial inflammation and remodeling, which resulted in elevated pulmonary arterial pressure (PAP) and ultimate rightsided heart failure. In the present study, Wistar rats were exposed to hypoxia for four weeks to induce PH. Multiomics approaches integrating 16S rRNA sequencing, untargeted and targeted metabolomics were utilized to identify alterations in gut microbiota and host metabolism associated with hypoxia-induced pulmonary hypertension. Rats exposed to hypoxia for four weeks exhibited the increased right ventricular systolic pressure (RVSP), pulmonary vascular remodeling, right ventricular hypertrophy, gut microbiota dysbiosis and disturbed serum metabolism. Tryptophan-pathway targeted metabolomics showed that chronic hypoxia exposure induced an increase of tryptophan, xanthurenic acid and 3-indoleacetic acid levels and a decrease of kynurenine, nicotinamide and kynurenic acid levels. Our research would offer promising targets for early diagnosis and treatment of PH.