Cushing Syndrome Is Associated With Gut Microbial Dysbiosis and Cortisol-Degrading Bacteria

作者：Minchun Zhang, Zhun Shi, Chao Wu, Fangming Yang, Tingwei Su, Xiaohuan Jing, Juan Shi, Huahui Ren, Lei Jiang, Yiran Jiang, Cui Zhang, Wenzhong Zhou, Yijing Zhou, Yijing Zhou, Kui Wu, Xu Zhong, Xu Zhong, Weiqiong Gu, Weiqiong Gu, Jiqiu Wang, Jiqiu Wang, Guang Ning, Ruixin Liu, Huanzi Zhong, Weiwei Zhou, Weiwei Zhou, Weiqing Wang · 发表于：The Journal of Clinical Endocrinology & Metabolism · 年份：2023 · DOI：10.1210/clinem/dgad766 · 被引用次数：25 · 研究领域：Gut microbiota and health、Adrenal Hormones and Disorders、Stress Responses and Cortisol

CONTEXT: Cushing syndrome (CS) is a severe endocrine disease characterized by excessive secretion of cortisol with multiple metabolic disorders. While gut microbial dysbiosis plays a vital role in metabolic disorders, the role of gut microbiota in CS remains unclear. OBJECTIVE: The objective of this work is to examine the alteration of gut microbiota in patients with CS. METHODS: We performed shotgun metagenomic sequencing of fecal samples from 78 patients with CS and 78 healthy controls matched for age and body mass index. Furthermore, we verify the cortisol degradation capacity of Ruminococcus gnavus in vitro and identify the potential metabolite by LC-MC/MS. RESULTS: We observed significant differences in microbial composition between CS and controls in both sexes, with CS showing reduced Bacteroidetes (Bacteroides vulgatus) and elevated Firmicutes (Erysipelotrichaceae_bacterium_6_1_45) and Proteobacteria (Enterobacter cloacae). Despite distinct causes of hypercortisolism in ACTH-dependent and ACTH-independent CS, we found no significant differences in metabolic profiles or gut microbiota between the 2 subgroups. Furthermore, we identified a group of gut species, including R. gnavus, that were positively correlated with cortisol levels in CS. These bacteria were found to harbor cortisol-degrading desAB genes and were consistently enriched in CS. Moreover, we demonstrated the efficient capacity of R. gnavus to degrade cortisol to 11-oxygenated androgens in vitro. CONCLUSION...