Gut microbiota signatures in primary aldosteronism and functional identification of an aldosterone-degrading gut bacterium

Primary aldosteronism (PA), a major cause of secondary hypertension, is characterized by autonomous aldosterone overproduction. Although the gut microbiota is closely linked to blood pressure regulation, its role in PA remains unclear. We performed metagenomic sequencing on fecal samples from 13 patients with essential hypertension (EH), 57 with unilateral PA (UPA), and 51 with bilateral PA (BPA). Despite comparable overall microbial diversity, gut microbial compositional differences were observed among EH and PA subtypes, particularly at finer taxonomic levels. We next identified 39 microbial species that were positively associated with plasma aldosterone concentration (PAC), and 29 that were negatively associated. In the co-abundance network, Ruminococcus gnavus emerged as one of the top three central nodes and was negatively correlated with PAC. Functionally, R. gnavus efficiently degraded aldosterone and multiple natural steroid hormones in vitro, and aldosterone degradation was accompanied by the generation of 3α,5β-tetrahydroaldosterone. R. gnavus-colonized germ-free mice showed reduced fecal aldosterone levels and downregulated expression of aldosterone downstream genes in the intestine. In an aldosterone infusion model, R. gnavus similarly decreased fecal aldosterone and improved systolic blood pressure (SBP) and serum potassium. Logistic regression further revealed that the presence of R. gnavus was associated with lower odds of having a historical highest SBP ≥ 160 mmHg in patients with PA. Collectively, this study reveals different gut microbial signatures in PA and highlights the aldosterone-metabolizing capacity and blood pressure regulation of R. gnavus. These findings advance our understanding of gut microbiota-steroid hormone interactions in PA and provide a basis for exploring microbiota-based stratification and intervention strategies in steroid hormone-related conditions.