Design Microbiome-Based Therapies to Prevent and Ameliorate Post-Traumatic Stress Disorder
Abstract
An estimated 2 million women Veterans live in the US today. Exposure to trauma is highly prevalent in U.S. women Veterans due to prolonged deployments with war zone exposure, combat-related injuries, and military sexual trauma. Post-traumatic stress disorder (PTSD) is a debilitating mental disorder that occurs in some persons after exposure to a traumatic event such as physical or sexual violence, combat, or a serious accident. At least 1 in 9 American women will meet lifetime criteria for a PTSD diagnosis, and women’s risk of PTSD is twice that of men. The prevalence of PTSD is significantly higher among women Veterans than women civilians and men Veterans. An estimated 20% of women Veterans who served in Iraq and Afghanistan have been diagnosed with PTSD. Women are the fastest growing group of Veterans, making up 9.4% of the Veteran population in 2014, which is estimated to increase to 16% by 2040. Among women, PTSD is also more likely to be chronic and is associated with worse functional impairment and distinct neurobiological profiles. Moreover, PTSD is a major risk factor for chronic diseases such as diabetes, coronary heart disease, stroke, and cardiometabolic disease in women. Understanding why some women develop PTSD and others do not is critical to inform prevention and intervention development. Although a substantial body of research has greatly improved our knowledge regarding prevalence, clinical symptoms, and consequences of PTSD over the last decades, much remains to be learned about why some persons are more vulnerable to developing PTSD after trauma, why some persons are resilient, and the mechanisms driving the relation between PTSD and chronic diseases. The potential role of the gut microbiome in mental health and a range of chronic diseases is increasingly recognized, although its role in PTSD specifically has yet to be understood. To date, only four studies have examined the PTSD–gut microbiome relationship. Moreover, these studies have several methodological limitations. The overarching challenge is that we do not fully understand the PTSD-gut microbiome relationship and hence lack rational design of microbiome-based therapeutics for the prevention or amelioration of PTSD. Our central hypothesis is that microbiome-based interventions can prevent and ameliorate PTSD. Our overall objective is to initiate a unique project to evaluate the PTSD-gut microbiome relationship and develop synbiotics (a combination of prebiotics and probiotics) to prevent or ameliorate PTSD, leveraging a population-based cohort and an etiologically relevant mouse model. To accomplish the overall objective, we have assembled a multidisciplinary team with expertise in human microbiome, trauma/PTSD epidemiology, resilience/positive health, molecular neurobiology, animal models of stress, and clinical microbiology. This team will pursue four research projects: Project 1. Differentiate the gut microbiome for women who develop PTSD following trauma versus those who are resilient and resistant in a population-based cohort. Project 2. Reveal the causation between PTSD versus resilience to trauma and gut microbiome using a novel computational method. Project 3. Quantify the impact of trauma exposure on the gut microbiome and neuronal activity using a mouse model. Project 4. Test whether microbiome-based interventions will reverse a CSDS-induced susceptibility phenotype in mice. Our proposed research is significant because it will provide foundational evidence to inform future studies on microbiome-targeted interventions for preventing or mitigating PTSD and its adverse consequences for physical health. This is directly relevant to the sub-area (3.a) of the three FY22 TBIPHRP FPA Focus Areas. The proposed research will offer a paradigm for the design of microbiome-based therapies to prevent and ameliorate PTSD. Posttraumatic Stress Disorder (PTSD) is a psychiatric condition that may occur
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310880
Entities
People
- Yang-Yu Liu
Organizations
- United States Army