Advisory Committee Chair
James Bibb
Advisory Committee Members
Gregory Kennedy
Matthew Macaluso
Document Type
Thesis
Date of Award
2022
Degree Name by School
Master of Science (MS) Heersink School of Medicine
Abstract
Chronic stress is a predisposing factor for various disease states, including neuropsychiatric disorders, such as depression and anxiety [1]. Stress-related disorders have complicated multifactorial etiologies [2]. Advances in psychotherapeutic and psychotropic treatments have occurred, but anxiety and depressive disorders are still prevalent and remain a burden to our societies [3]. More than 30% of major depressive disorder patients fail to remission despite an FDAapproved medication [4]. Meanwhile, the contribution of microbiota-gut-brain axis signaling in both etiologies and treatment of stress-related disorders is increasingly being recognized [5]. More evidence has shown that the gut microbiota has the potential to alter the host’s mental state via neural, endocrine, and immune pathways [6]. Administration of probiotics, fecal microbiota transplantation, and antibiotic supplementation are currently being evaluated as potential strategies to modulate the gut microbiome and assess how such modulation may affect the brain and behavioral function [7]. In this study, we investigate the effects of the supplementation of vancomycin, a non-absorbable antibiotic that doesn’t cross the blood-brain barrier on iv the contraction of detrimental neurobehavioral effects of chronic unpredictable stress (CUS). Our results indicate that chronic stress-induced anxio-depressive behaviors are attenuated in vancomycin-supplemented mice whereas vancomycin supplementation in non-stressed mice has no substantial effects on anxio-depressive behaviors. Analysis of gut microbiota reveals that the composition changes in gut microbiota in CUS-treated mice match with human patients suffering from mental illnesses. Supplementing with vancomycin reverses these changes. Similarly, we noticed the decreases in serum tryptophan and its related metabolites levels in CUS-treated mice, and vancomycin supplementation reverses the alternations caused by stress. Our quantitative immunoblotting confirms that CUS alters phosphorylation states of CDK5 and PKA signaling pathways in the ventral striatum, which have been linked to neuropsychiatric diseases [8]. Our results support the insights and may help formulate novel therapeutic strategies while advancing our understanding of the basis of stress-related mental illness.
Recommended Citation
Huang, Yuang-Tai, "A Gastrointestinal-Specific Antibiotic as an Experimental Treatment for Anxio-Depressive Disorders" (2022). All ETDs from UAB. 120.
https://digitalcommons.library.uab.edu/etd-collection/120