Gut microbiome dysbiosis is associated with aldosterone overproduction in idiopathic hyperaldosteronism

Idiopathic hyperaldosteronism (IHA) is a significant cause of secondary hypertension. Emerging evidence links the gut microbiota to endocrine and cardiovascular diseases. We integrated human genetics, multi-omics, and fecal microbiota transplantation (FMT) to investigate the association between IHA and gut microbiome. Two-sample Mendelian randomization identified seven bacterial taxa associated with IHA. Metagenomic analysis of 30 patients with IHA and 30 healthy control subjects revealed lower microbial diversity and depletion of protective genera identified by Mendelian randomization. Plasma metabolomics showed alterations in tryptophan metabolism and other metabolic pathways that overlapped with microbial functional changes. Tryptophan-derived metabolites correlated with the abundance of protective genera. FMT from patients with IHA increased serum aldosterone and elevated 5-hydroxy-L-tryptophan in germ-free mice. These findings support an association between gut microbiome dysbiosis, metabolic alterations, and aldosterone dysregulation, highlighting the gut microbiome as a potential target for the diagnosis and treatment of IHA.