AUTHOR=Zhang Qin , Hu Wen-mu , Deng Yu-ling , Wan Jin-jing , Wang Yu-jun , Jin Ping 

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

JOURNAL=Frontiers in Endocrinology

VOLUME=Volume 13 - 2022

YEAR=2023

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2022.1095438

DOI=10.3389/fendo.2022.1095438

ISSN=1664-2392

ABSTRACT=<sec><title>Objective</title><p>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).</p></sec><sec><title>Methods</title><p>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).</p></sec><sec><title>Results</title><p>Compared to the controls, the Simpson and Pielou indices of α diversity were dramatically decreased in Cushing’s syndrome (<italic>P</italic> &lt; 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 <italic>Proteobacteria</italic> and <italic>Escherichia-Shigella</italic>, and depleted in <italic>Firmicutes</italic>, including <italic>Agathobacter</italic>, <italic>Blautia</italic>, <italic>Anaerostipes</italic>, <italic>Eubacterium_eligens_group</italic>, and <italic>Lachnospira</italic>. Spearman analysis demonstrated that HbA1c, SBP, DBP, and cortisol levels were significantly positively correlated with <italic>Proteobacteria</italic> and <italic>Escherichia-Shigella</italic>, whereas negatively correlated with <italic>Agathobacter, Blautia, Anaerostipes, Eubacterium_hallii_group, and Lachnospira</italic>, etc. Cushing’s syndrome patients also had a lower propionic acid concentration (0.151±0.054 <italic>vs.</italic> 0.205±0.032 µg/mL, <italic>P</italic>=0.039) than controls. Furthermore, the level of propionic acid was negatively correlated with systolic pressure and cortisol levels (<italic>P</italic>&lt;0.05).</p></sec><sec><title>Conclusion</title><p>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.</p></sec>