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Gut dysbiosis-induced vitamin B6 metabolic disorder contributes to chronic stress-related abnormal behaviors in a cortisol-independent manner

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Title: Gut dysbiosis-induced vitamin B6 metabolic disorder contributes to chronic stress-related abnormal behaviors in a cortisol-independent manner
Authors: Wenxiang Qing, Huimin Chen, Xin Ma, Jie Chen, Yuan Le, Hui Chen, Jianhua Tong, Kaiming Duan, Daqing Ma, Wen Ouyang, Jianbin Tong
Source: Gut Microbes, Vol 17, Iss 1 (2025)
Publisher Information: Taylor & Francis Group, 2025.
Publication Year: 2025
Collection: LCC:Diseases of the digestive system. Gastroenterology
Subject Terms: Chronic stress, gut microbial dysbiosis, vitamin B6, restraint stress, Diseases of the digestive system. Gastroenterology, RC799-869
More Details: 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.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 19490976
1949-0984
1949-0976
Relation: https://doaj.org/toc/1949-0976; https://doaj.org/toc/1949-0984
DOI: 10.1080/19490976.2024.2447824
Access URL: https://doaj.org/article/f30da62f25544dd0929f0f99955c67f5
Accession Number: edsdoj.f30da62f25544dd0929f0f99955c67f5
Database: Directory of Open Access Journals
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  Data: Gut dysbiosis-induced vitamin B6 metabolic disorder contributes to chronic stress-related abnormal behaviors in a cortisol-independent manner
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  Data: <searchLink fieldCode="AR" term="%22Wenxiang+Qing%22">Wenxiang Qing</searchLink><br /><searchLink fieldCode="AR" term="%22Huimin+Chen%22">Huimin Chen</searchLink><br /><searchLink fieldCode="AR" term="%22Xin+Ma%22">Xin Ma</searchLink><br /><searchLink fieldCode="AR" term="%22Jie+Chen%22">Jie Chen</searchLink><br /><searchLink fieldCode="AR" term="%22Yuan+Le%22">Yuan Le</searchLink><br /><searchLink fieldCode="AR" term="%22Hui+Chen%22">Hui Chen</searchLink><br /><searchLink fieldCode="AR" term="%22Jianhua+Tong%22">Jianhua Tong</searchLink><br /><searchLink fieldCode="AR" term="%22Kaiming+Duan%22">Kaiming Duan</searchLink><br /><searchLink fieldCode="AR" term="%22Daqing+Ma%22">Daqing Ma</searchLink><br /><searchLink fieldCode="AR" term="%22Wen+Ouyang%22">Wen Ouyang</searchLink><br /><searchLink fieldCode="AR" term="%22Jianbin+Tong%22">Jianbin Tong</searchLink>
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  Data: Gut Microbes, Vol 17, Iss 1 (2025)
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  Data: <searchLink fieldCode="DE" term="%22Chronic+stress%22">Chronic stress</searchLink><br /><searchLink fieldCode="DE" term="%22gut+microbial+dysbiosis%22">gut microbial dysbiosis</searchLink><br /><searchLink fieldCode="DE" term="%22vitamin+B6%22">vitamin B6</searchLink><br /><searchLink fieldCode="DE" term="%22restraint+stress%22">restraint stress</searchLink><br /><searchLink fieldCode="DE" term="%22Diseases+of+the+digestive+system%2E+Gastroenterology%22">Diseases of the digestive system. Gastroenterology</searchLink><br /><searchLink fieldCode="DE" term="%22RC799-869%22">RC799-869</searchLink>
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  Data: 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.
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      – SubjectFull: vitamin B6
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