Gut microbiota, metabolites, and pulmonary hypertension: Mutual regulation and potential therapies

Pulmonary hypertension is a progressive condition characterized by increased pulmonary vascular pressure and resistance, ultimately leading to right heart failure and death. Increasing evidence has underscored the importance of the gut-lung axis in the development of respiratory and cardiovascular diseases. Notably, significant changes in the gut microbiota, including altered microbial composition and function, have been observed in pulmonary hypertension. Specifically, microbiota-derived metabolites, including short chain fatty acids, trimethylamine N-oxide, bile acids and tryptophan, play a significant role in the development of pulmonary hypertension. The identification of key bacteria and metabolites, along with recent advances in gut microbiota-targeting technologies and metabolic pathway-targeting inhibitors/agonists, holds potential for developing diagnostic, prognostic, and therapeutic strategies for pulmonary hypertension. Emerging research directions include metagenomic analysis of viruses and fungi, artificial intelligence-aided prediction models, novel metabolites and their associated enzymes, drug-microbiota interactions, selective antibiotics, and advanced microbiota transplantation. This review synthesizes clinical and experimental evidence linking the gut microbiota to pulmonary hypertension, highlighting their interplay as a promising avenue for further investigation and translational applications.