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Publication : Stress-induced mucin 13 reductions drive intestinal microbiome shifts and despair behaviors.

First Author  Rivet-Noor CR Year  2024
Journal  Brain Behav Immun Volume  119
Pages  665-680 PubMed ID  38579936
Mgi Jnum  J:352635 Mgi Id  MGI:7627813
Doi  10.1016/j.bbi.2024.03.028 Citation  Rivet-Noor CR, et al. (2024) Stress-induced mucin 13 reductions drive intestinal microbiome shifts and despair behaviors. Brain Behav Immun 119:665-680
abstractText  Depression is a prevalent psychological condition with limited treatment options. While its etiology is multifactorial, both chronic stress and changes in microbiome composition are associated with disease pathology. Stress is known to induce microbiome dysbiosis, defined here as a change in microbial composition associated with a pathological condition. This state of dysbiosis is known to feedback on depressive symptoms. While studies have demonstrated that targeted restoration of the microbiome can alleviate depressive-like symptoms in mice, translating these findings to human patients has proven challenging due to the complexity of the human microbiome. As such, there is an urgent need to identify factors upstream of microbial dysbiosis. Here we investigate the role of mucin 13 as an upstream mediator of microbiome composition changes in the context of stress. Using a model of chronic stress, we show that the glycocalyx protein, mucin 13, is selectively reduced after psychological stress exposure. We further demonstrate that the reduction of Muc13 is mediated by the Hnf4 transcription factor family. Finally, we determine that deleting Muc13 is sufficient to drive microbiome shifts and despair behaviors. These findings shed light on the mechanisms behind stress-induced microbial changes and reveal a novel regulator of mucin 13 expression.
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