Cushing's Syndrome is associated with Gut Microbial Dysbiosis and Cortisol-Degrading Bacteria
© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissionsoup.com..
CONTEXT: Cushing's Syndrome (CS) is a severe endocrine disease characterized by excessive secretion of cortisol with multiple metabolic disorders. While gut 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 two subgroups. Furthermore, we identified a group of gut species, including R. gnavus, 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.
CONCLUSIONS: This study provides evidence of gut microbial dysbiosis in patients with CS and identifies a group of CS-enriched bacteria capable of degrading cortisol. These findings highlight the potential role of gut microbiota in regulating host steroid hormone levels, and consequently host health.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2023 |
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| Enthalten in: |
The Journal of clinical endocrinology and metabolism - (2023) vom: 29. Dez. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhang, Minchun [VerfasserIn] |
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| Links: |
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| Themen: |
Cortisol |
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| Anmerkungen: |
Date Revised 29.12.2023 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1210/clinem/dgad766 |
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| 100 | 1 | |a Zhang, Minchun |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Cushing's Syndrome is associated with Gut Microbial Dysbiosis and Cortisol-Degrading Bacteria |
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| 500 | |a published: Print-Electronic | ||
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| 520 | |a © The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissionsoup.com. | ||
| 520 | |a CONTEXT: Cushing's Syndrome (CS) is a severe endocrine disease characterized by excessive secretion of cortisol with multiple metabolic disorders. While gut dysbiosis plays a vital role in metabolic disorders, the role of gut microbiota in CS remains unclear | ||
| 520 | |a OBJECTIVE: The objective of this work is to examine the alteration of gut microbiota in patients with CS | ||
| 520 | |a 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 | ||
| 520 | |a 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 two subgroups. Furthermore, we identified a group of gut species, including R. gnavus, 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 | ||
| 520 | |a CONCLUSIONS: This study provides evidence of gut microbial dysbiosis in patients with CS and identifies a group of CS-enriched bacteria capable of degrading cortisol. These findings highlight the potential role of gut microbiota in regulating host steroid hormone levels, and consequently host health | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Ruminococcus gnavus | |
| 650 | 4 | |a Cortisol | |
| 650 | 4 | |a Cushing’s Syndrome | |
| 650 | 4 | |a Gut Microbiome | |
| 700 | 1 | |a Shi, Zhun |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Chao |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Fangming |e verfasserin |4 aut | |
| 700 | 1 | |a Su, Tingwei |e verfasserin |4 aut | |
| 700 | 1 | |a Jing, Xiaohuan |e verfasserin |4 aut | |
| 700 | 1 | |a Shi, Juan |e verfasserin |4 aut | |
| 700 | 1 | |a Ren, Huahui |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Lei |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Yiran |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Cui |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Wenzhong |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Yijing |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Kui |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Sichang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhong, Xu |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Luming |e verfasserin |4 aut | |
| 700 | 1 | |a Gu, Weiqiong |e verfasserin |4 aut | |
| 700 | 1 | |a Hong, Jie |e verfasserin |4 aut | |
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| 700 | 1 | |a Liu, Ruixin |e verfasserin |4 aut | |
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| 700 | 1 | |a Zhou, Weiwei |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Weiqing |e verfasserin |4 aut | |
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