Abstract

Stress can lead to gut dysbiosis in brain-gut axis disordered diseases as irritable bowel syndrome (IBS), yet the mechanisms how stress transfer from the brain to the gut and disrupt gut microbiota remain elusive. Here we describe a stress-responsive brain-to-gut axis which impairs colonocytes’ mitochondria to trigger gut dysbiosis. Patients with IBS exhibit significantly increased facultative anaerobes and decreased obligate anaerobes, related to increased serum corticotropin-releasing hormone (CRH) level and defected colonocytes’ mitochondria ultrastructure. Mice exposed to acute stress experienced enhanced CRH-CRH receptor type 1 (CRHR1) signaling, which impaired mitochondria and epithelium hypoxia in the colon, subsequently triggered gut dysbiosis. Antagonizing CRHR1 expression to inhibit cAMP/Ras/MAPK signaling or activating mitochondria respiration conferred resilience against stress-induced mitochondria damaging and epithelium hypoxia impairment, ultimately improving gut dysbiosis. These results suggest that the CRH-CRHR1-mitochondria pathway plays a pivotal role in stress-induced gut dysbiosis that could be therapeutically targeted for stress-induced gastrointestinal diseases.

Details

Title
Stress triggers gut dysbiosis via CRH-CRHR1-mitochondria pathway
Author
Zhang, Yiming 1 ; Li, Xiaoang 1 ; Lu, Siqi 1 ; Guo, Huaizhu 1 ; Zhang, Zhuangyi 1 ; Zheng, Haonan 1 ; Zhang, Cunzheng 1 ; Zhang, Jindong 1 ; Wang, Kun 1 ; Pei, Fei 2 ; Duan, Liping 1 

 Peking University Third Hospital, Haidian District, Department of Gastroenterology, Beijing, China (GRID:grid.411642.4) (ISNI:0000 0004 0605 3760); Haidian District, Beijing Key Laboratory for Helicobacter pylori Infection and Upper Gastrointestinal Diseases, Beijing, China (GRID:grid.414252.4) (ISNI:0000 0004 1761 8894) 
 Peking University Third Hospital, Peking University School of Basic Medical Sciences, Department of Pathology, Beijing, China (GRID:grid.11135.37) (ISNI:0000 0001 2256 9319) 
Pages
93
Publication year
2024
Publication date
2024
Publisher
Nature Publishing Group
e-ISSN
20555008
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3111349291
Copyright
© The Author(s) 2024. This work is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.