Gut dysbiosis-induced vitamin B6 metabolic disorder contributes to chronic stress-related abnormal behaviors in a cortisol-independent manner
Chronic stress can result in various conditions, including psychological disorders, neurodegenerative diseases, and accelerated brain aging. Gut dysbiosis potentially contributes to stress-related brain disorders in individuals with chronic stress. However, the causal relationship and key factors be...
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| Format: | Article |
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Taylor & Francis Group
2025-12-01
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| Series: | Gut Microbes |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19490976.2024.2447824 |
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| author | Wenxiang Qing Huimin Chen Xin Ma Jie Chen Yuan Le Hui Chen Jianhua Tong Kaiming Duan Daqing Ma Wen Ouyang Jianbin Tong |
| author_facet | Wenxiang Qing Huimin Chen Xin Ma Jie Chen Yuan Le Hui Chen Jianhua Tong Kaiming Duan Daqing Ma Wen Ouyang Jianbin Tong |
| author_sort | Wenxiang Qing |
| collection | DOAJ |
| description | Chronic stress can result in various conditions, including psychological disorders, neurodegenerative diseases, and accelerated brain aging. Gut dysbiosis potentially contributes to stress-related brain disorders in individuals with chronic stress. However, the causal relationship and key factors between gut dysbiosis and brain disorders in chronic stress remain elusive, particularly under non-sterile conditions. Here, using a repeated restraint stress (RRS) rat model, we show that sequential transplantation of the cecal contents of different RRS stages to normal rats reproduced RRS-induced core phenotypes, including abnormal behaviors, increased peripheral blood corticosterone and inflammatory cytokines, and a unique gut microbial phenotype. This core phenotypic development was effectively inhibited with probiotic supplement. The RRS-induced unique gut microbial phenotypes at the genus level were positively or negatively associated with the levels of 20 plasma metabolites, including vitamin B6 metabolites 4-pyridoxic acid and 4-pyridoxate. Vitamin B6 supplement during RRS alleviated weight loss, abnormal behaviors, peripheral inflammation, and neuroinflammation, but did not affect the peripheral corticosterone levels in chronic stressed rats. Dampening inflammatory signaling via knocking out caspase 11 or caspase 1 inhibitor abolished RRS-induced abnormal behaviors and peripheral and neuroinflammation but did not decrease peripheral corticosterone in mice. These findings show that gut dysbiosis-induced vitamin B6 metabolism disorder is a new non-hypothalamic-pituitary-adrenal axis mechanism of chronic stress-related brain disorders. Both probiotics and vitamin B6 supplement have potential to be developed as therapeutic strategies for preventing and/or treating chronic stress-related illness. |
| format | Article |
| id | doaj-art-f30da62f25544dd0929f0f99955c67f5 |
| institution | Kabale University |
| issn | 1949-0976 1949-0984 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Gut Microbes |
| spelling | doaj-art-f30da62f25544dd0929f0f99955c67f52025-01-08T04:41:18ZengTaylor & Francis GroupGut Microbes1949-09761949-09842025-12-0117110.1080/19490976.2024.2447824Gut dysbiosis-induced vitamin B6 metabolic disorder contributes to chronic stress-related abnormal behaviors in a cortisol-independent mannerWenxiang Qing0Huimin Chen1Xin Ma2Jie Chen3Yuan Le4Hui Chen5Jianhua Tong6Kaiming Duan7Daqing Ma8Wen Ouyang9Jianbin Tong10Department of Anesthesiology, Third Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Anesthesiology, Third Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Anesthesiology, Third Xiangya Hospital, Central South University, Changsha, Hunan, ChinaHunan Province Key Laboratory of Brain Homeostasis, Third Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Anesthesiology, Third Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Anesthesiology, Third Xiangya Hospital, Central South University, Changsha, Hunan, ChinaHunan Provincial Key Laboratory of Phytohormones and Growth Development, Hunan Agricultural University, Changsha, ChinaDepartment of Anesthesiology, Third Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDivision of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital, London, UKDepartment of Anesthesiology, Third Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Anesthesiology, Third Xiangya Hospital, Central South University, Changsha, Hunan, ChinaChronic stress can result in various conditions, including psychological disorders, neurodegenerative diseases, and accelerated brain aging. Gut dysbiosis potentially contributes to stress-related brain disorders in individuals with chronic stress. However, the causal relationship and key factors between gut dysbiosis and brain disorders in chronic stress remain elusive, particularly under non-sterile conditions. Here, using a repeated restraint stress (RRS) rat model, we show that sequential transplantation of the cecal contents of different RRS stages to normal rats reproduced RRS-induced core phenotypes, including abnormal behaviors, increased peripheral blood corticosterone and inflammatory cytokines, and a unique gut microbial phenotype. This core phenotypic development was effectively inhibited with probiotic supplement. The RRS-induced unique gut microbial phenotypes at the genus level were positively or negatively associated with the levels of 20 plasma metabolites, including vitamin B6 metabolites 4-pyridoxic acid and 4-pyridoxate. Vitamin B6 supplement during RRS alleviated weight loss, abnormal behaviors, peripheral inflammation, and neuroinflammation, but did not affect the peripheral corticosterone levels in chronic stressed rats. Dampening inflammatory signaling via knocking out caspase 11 or caspase 1 inhibitor abolished RRS-induced abnormal behaviors and peripheral and neuroinflammation but did not decrease peripheral corticosterone in mice. These findings show that gut dysbiosis-induced vitamin B6 metabolism disorder is a new non-hypothalamic-pituitary-adrenal axis mechanism of chronic stress-related brain disorders. Both probiotics and vitamin B6 supplement have potential to be developed as therapeutic strategies for preventing and/or treating chronic stress-related illness.https://www.tandfonline.com/doi/10.1080/19490976.2024.2447824Chronic stressgut microbial dysbiosisvitamin B6restraint stress |
| spellingShingle | Wenxiang Qing Huimin Chen Xin Ma Jie Chen Yuan Le Hui Chen Jianhua Tong Kaiming Duan Daqing Ma Wen Ouyang Jianbin Tong Gut dysbiosis-induced vitamin B6 metabolic disorder contributes to chronic stress-related abnormal behaviors in a cortisol-independent manner Gut Microbes Chronic stress gut microbial dysbiosis vitamin B6 restraint stress |
| title | Gut dysbiosis-induced vitamin B6 metabolic disorder contributes to chronic stress-related abnormal behaviors in a cortisol-independent manner |
| title_full | Gut dysbiosis-induced vitamin B6 metabolic disorder contributes to chronic stress-related abnormal behaviors in a cortisol-independent manner |
| title_fullStr | Gut dysbiosis-induced vitamin B6 metabolic disorder contributes to chronic stress-related abnormal behaviors in a cortisol-independent manner |
| title_full_unstemmed | Gut dysbiosis-induced vitamin B6 metabolic disorder contributes to chronic stress-related abnormal behaviors in a cortisol-independent manner |
| title_short | Gut dysbiosis-induced vitamin B6 metabolic disorder contributes to chronic stress-related abnormal behaviors in a cortisol-independent manner |
| title_sort | gut dysbiosis induced vitamin b6 metabolic disorder contributes to chronic stress related abnormal behaviors in a cortisol independent manner |
| topic | Chronic stress gut microbial dysbiosis vitamin B6 restraint stress |
| url | https://www.tandfonline.com/doi/10.1080/19490976.2024.2447824 |
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