Gut dysbiosis-induced vitamin B6 metabolic disorder contributes to chronic stress-related abnormal behaviors in a cortisol-independent manner
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Le résumé fourni par la source
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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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Gut dysbiosis-induced vitamin B6 metabolic disorder contributes to chronic stress-related abnormal behaviors in a cortisol-independent manner
- Date Crossref
- 07/01/2025
- Éditeur
- Informa UK Limited
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Central South University Department of Anesthesiology pays non établi dans la noticeUniversité ou école supérieure
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Third Xiangya Hospital pays non établi dans la noticeÉtablissement de santé
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Kunming University of Science and Technology pays non établi dans la noticeUniversité ou école supérieure
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First People's Hospital of Yunnan Province Department of Anesthesiology pays non établi dans la noticeÉtablissement de santé
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The First People's Hospital of Xiaoshan District pays non établi dans la noticeÉtablissement de santé
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Hunan Agricultural University Hunan Provincial Key Laboratory of Phytohormones and Growth Development pays non établi dans la noticeUniversité ou école supérieure
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Chelsea and Westminster Hospital pays non établi dans la noticeÉtablissement de santé
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Imperial College London pays non établi dans la noticeUniversité ou école supérieure
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Xishan District pays non établi dans la noticeInstitution
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Faculty of Medicine Department of Surgery and Cancer pays non établi dans la noticeUniversité ou école supérieure
Department of Anesthesiology — Central South University, Third Xiangya Hospital et Kunming University of Science and Technology, avec 7 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.