Tryptophan metabolism: a potential link between the gut microbiota and pulmonary vascular remodeling in pulmonary hypertension

Pulmonary hypertension (PH) comprises a group of cardiopulmonary disorders characterized by a sustained increase in pulmonary vascular resistance and pulmonary vascular remodeling, with disease progression potentially leading to right heart failure and death. Current therapies can improve symptoms and hemodynamics in some patients, but effective means of reversing established structural pulmonary vascular remodeling remain lacking. Gut microbial dysbiosis, intestinal barrier injury, and altered microbial metabolism have been proposed to contribute to the development and progression of PH. Tryptophan metabolism is jointly regulated by host tissues, immune cells, and gut microorganisms and serves as a key hub linking the host and its commensal microbiota. The kynurenine, serotonin, and indole pathways may participate in pulmonary vascular remodeling by influencing pulmonary vascular tone, endothelial homeostasis, pulmonary arterial smooth muscle cell phenotype, inflammation, oxidative stress, and cellular metabolism, although the precise mechanisms remain to be clarified. This review systematically summarizes current evidence on the involvement of the gut microbiota and tryptophan metabolism in pulmonary vascular remodeling in PH, with emphasis on the available evidence, potential therapeutic targets, and prospects for clinical translation, thereby providing a basis for further investigation of the metabolic regulation of PH and the development of new intervention strategies.