Chronic Stress Exposure Alters the Gut Barrier: Sex-Specific Effects on Microbiota and Jejunum Tight Junctions
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Le résumé fourni par la source
Background: Major depressive disorder (MDD) is the leading cause of disability worldwide. Of individuals with MDD, 30% to 50% are unresponsive to common antidepressants, highlighting untapped causal biological mechanisms. Dysfunction in the microbiota-gut-brain axis has been implicated in MDD pathogenesis. Exposure to chronic stress disrupts blood-brain barrier integrity; still, little is known about intestinal barrier function in these conditions, particularly for the small intestine, where absorption of most foods and drugs takes place. Methods: We investigated how chronic social or variable stress, two mouse models of depression, impact the jejunum intestinal barrier in males and females. Mice were subjected to stress paradigms followed by analysis of gene expression profiles of intestinal barrier-related targets, fecal microbial composition, and blood-based markers. Results: Altered microbial populations and changes in gene expression of jejunum tight junctions were observed depending on the type and duration of stress, with sex-specific effects. We used machine learning to characterize in detail morphological tight junction properties, identifying a cluster of ruffled junctions in stressed animals. Junctional ruffling is associated with inflammation, so we evaluated whether lipopolysaccharide injection recapitulates stress-induced changes in the jejunum and observed profound sex differences. Finally, lipopolysaccharide-binding protein, a marker of gut barrier leakiness, was associated with stress vulnerability in mice, and translational value was confirmed on blood samples from women with MDD. Conclusions: Our results provide evidence that chronic stress disrupts intestinal barrier homeostasis in conjunction with the manifestation of depressive-like behaviors in a sex-specific manner in mice and, possibly, in human depression.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Chronic Stress Exposure Alters the Gut Barrier: Sex-Specific Effects on Microbiota and Jejunum Tight Junctions
- Date Crossref
- 01/01/2024
- Éditeur
- Elsevier BV
- 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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Université Laval Department of Computer Science and Software Engineering and Department of Electrical and Computer Engineering pays non établi dans la noticeUniversité ou école supérieure
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University of Ottawa Department of Cellular and Molecular Medicine pays non établi dans la noticeUniversité ou école supérieure
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Douglas Mental Health University Institute pays non établi dans la noticeÉtablissement de santé
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McGill University pays non établi dans la noticeUniversité ou école supérieure
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Faculty of Medicine and CERVO Brain Research Center Department of Psychiatry and Neuroscience pays non établi dans la noticeUniversité ou école supérieure
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School of Nutrition Sciences pays non établi dans la noticeUniversité ou école supérieure
Department of Computer Science and Software Engineering and Department of Electrical and Computer Engineering — Université Laval, Department of Cellular and Molecular Medicine — University of Ottawa et Douglas Mental Health University Institute, avec 3 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.