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

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

Brain, behavior, and immunity (2024-04-06)
Courtney R Rivet-Noor, Andrea R Merchak, Caroline Render, Naudia M Gay, Rebecca M Beiter, Ryan M Brown, Austin Keeler, G Brett Moreau, Sihan Li, Deniz G Olgun, Alexandra D Steigmeyer, Rachel Ofer, Tobey Phan, Kiranmayi Vemuri, Lei Chen, Keira E Mahoney, Jung-Bum Shin, Stacy A Malaker, Chris Deppmann, Michael P Verzi, Alban Gaultier
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Hydrocortisone, ≥98% (HPLC)
Sigma-Aldrich
HNF4 Antagonist, BI6015, The HNF4 Antagonist, BI6, also referenced under CAS 93987-29-2, controls the biological activity of HNF4.
Roche
cOmplete, Mini, EDTA-free Protease Inhibitor Cocktail, Protease Inhibitor Cocktail Tablets provided in a glass vial, Tablets provided in a glass vial