Photo Credit: HT Ganzo

The following is a summary of “Cushing Syndrome Is Associated With Gut Microbial Dysbiosis and Cortisol-Degrading Bacteria,” published in the June 2024 issue of Endocrinology by Zhang, et al.

Cushing syndrome (CS) is a serious endocrine disorder characterized by excessive cortisol secretion, which leads to various metabolic disorders. While gut microbial dysbiosis is known to contribute to metabolic disturbances, its role in CS remains unclear. For a study, researchers sought to investigate the alteration of gut microbiota in patients with CS to better understand its potential role in the pathogenesis of the syndrome.

Shotgun metagenomic sequencing of fecal samples was conducted on 78 patients with CS and 78 age- and body-mass index-matched healthy controls. The study also assessed the cortisol degradation capacity of Ruminococcus gnavus in vitro and identified potential metabolites using LC-MC/MS.

Significant differences in microbial composition were observed between patients with CS and controls, showing reduced levels of Bacteroidetes (particularly Bacteroides vulgatus) and elevated levels of Firmicutes (such as Erysipelotrichaceae_bacterium_6_1_45) and Proteobacteria (including Enterobacter cloacae). Despite different etiologies for hypercortisolism in ACTH-dependent and ACTH-independent CS, no significant differences in metabolic profiles or gut microbiota were found between these subgroups. A group of gut species, including R. gnavus, were positively correlated with cortisol levels in patients with CS and harbored cortisol-degrading desAB genes. These bacteria were consistently enriched in patients with CS. Additionally, R. gnavus was demonstrated to degrade cortisol to 11-oxygenated androgens in vitro efficiently.

The study provided evidence of gut microbial dysbiosis in patients with CS and identified a group of bacteria capable of degrading cortisol. The findings suggested a potential role of gut microbiota in regulating host steroid hormone levels and overall host health.

Reference: academic.oup.com/jcem/article-abstract/109/6/1474/7503830