Dysbiosis of gut microbiota and decreased propionic acid associated with metabolic abnormality in Cushing’s syndrome

Objective Chronic hypercortisolism leads to a phenotype resembling metabolic syndrome. We aimed to investigate the association between gut microbiota and metabolic abnormalities in endogenous hypercortisolism (Cushing’s syndrome). Methods A total of 23 patients with Cushing’s syndrome (18 female and 5 men, aged 47.24 ± 12.99 years) and 30 age-, sex-and BMI-matched healthy controls (18 female and 12 men, aged 45.03 ± 6.69 years) were consecutively recruited. Differences in gut microbiota and plasma short-chain fatty acid (SCFAs) concentrations between the Cushing’s syndrome patients and controls were analyzed by 16S rRNA sequencing and gas chromatography-mass spectrometry (GC-MS). Results Compared to the controls, the Simpson and Pielou indices of α diversity were dramatically decreased in Cushing’s syndrome ( P < 0.05). The gut microbiota community structure differed significantly between Cushing’s syndrome patients and controls. Compared to controls, the bacterial communities of the Cushing’s syndrome patients were enriched in Proteobacteria and Escherichia-Shigella , and depleted in Firmicutes , including Agathobacter , Blautia , Anaerostipes , Eubacterium_eligens_group , and Lachnospira . Spearman analysis demonstrated that HbA1c, SBP, DBP, and cortisol levels were significantly positively correlated with Proteobacteria and Escherichia-Shigella , whereas negatively correlated with Agathobacter, Blautia, Anaerostipes, Eubacterium_hallii_group, and Lachnospira , etc. Cushing’s syndrome patients also had a lower propionic acid concentration (0.151±0.054 vs. 0.205±0.032 µg/mL, P =0.039) than controls. Furthermore, the level of propionic acid was negatively correlated with systolic pressure and cortisol levels ( P <0.05). Conclusion Gut microbiota dysbiosis and decreased propionic acid levels were observed in patients with Cushing’s, suggesting that the gut microbiota may be a potential therapeutic intervention target to improve hypercortisolism-related metabolic abnormalities.