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

Abstract

ObjectiveChronic 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).MethodsA 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).ResultsCompared 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).ConclusionGut 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.

Gut microbiota dysbiosis and decreased levels of acetic and propionic acid participate in glucocorticoid-induced glycolipid metabolism disorder

“…In our study, we observed noticeable gut microbiota dysbiosis in mouse models with GC-induced glycolipid metabolism disorder. Interestingly, some bacteria were shared in the patients with endogenous hypercortisolism and the mouse model used in this study, such as the increased abundance of Proteobacteria and decreased abundance of short-chain fatty acid-producing bacteria, including Lachnospiraceae , Eubacterium spp., and Faecalibacterium ( 12 ). The level of serum propionic acid also decreased significantly in both the patients and the mouse model.…”

“…However, reports on SCFAs and GC-induced glycolipid metabolism disorders are rare. Our previous study found that the level of propionic acid was significantly decreased in patients with endogenous glucocorticoid excess ( 12 ). Qiu et al also found that SCFA content was decreased in GC-induced obese individuals ( 11 ).…”

“…In contrast, patients with Cushing’s syndrome have a prolonged increase in endogenous glucocorticoids, the condition of which offers an opportunity to better reflect the influence of glucocorticoids on gut microbiota disorders. Thus, we investigated the gut microbiota and plasma short-chain fatty acids (SCFAs) in patients with endogenous hypercortisolism (Cushing’s syndrome; 12 ). We found that the α diversity of the gut microbiota was dramatically decreased in patients with endogenous hypercortisolism.…”

“…We found that the α diversity of the gut microbiota was dramatically decreased in patients with endogenous hypercortisolism. Compared to controls, the patients with endogenous hypercortisolism were enriched in Proteobacteria and depleted in Lachnospiraceae and Faecalibacterium ( 12 ).…”

Gut microbial dysbiosis in patients with Cushing’s disease in long-term remission. Relationship with cardiometabolic risk

“…Interestingly, Zhang et al. recently showed that serum levels of propionic acid, one of the most abundant SCFAs, which is thought to promote favourable metabolic changes and protect against diet-induced obesity, were reduced in 23 patients with active CS as compared with controls ( 27 ). In agreement with our results, a relative scarcity of Firmicutes has also been documented in these patients, supporting our hypothesis that dysbiosis related to cortisol excess may persist long-term despite biochemical remission ( 27 )…”