Prebiotic and Probiotic Interventions for Treatment of TBI-Induced Microbiome Dysfunction
Abstract
Traumatic brain injury (TBI) is a major health concern for the military and for society at large. In military populations, over 450,000 brain injury have been recorded by the DOD since 2000. These injuries have wide-ranging consequences that often last years beyond the initial injury event. For instance, military populations with TBI are at higher risk for several psychiatric conditions and have elevated rates of psychiatric impairments. A hallmark across many disorders is risky decision-making. Currently, there are no treatments for TBI or for the conditions that develop because of TBI. The mechanisms by which TBI may cause such symptoms are complex. Moreover, these factors are often difficult to tease apart in patient populations for both practical and ethical reasons. To better study TBI mechanisms, we can use an animal model that mimics many of the conditions of human TBI. Our laboratory has established a rat model of TBI that demonstrates risky decision-making using a rodent gambling task. This assessment directly mimics a human neuropsychological assessment, the Iowa Gambling Task, which patients with TBI struggle with. Measurements of the gut microbiome, the community of stomach and colon bacteria that help to process nutrients, show acute and chronic disruptions in patients with TBI. Our rat model mimics these findings and low gut bacterial diversity actually predict worse impairments on the rodent gambling task. Further, our pilot data shows that intervention can rescue some of these deficits. Thus, the goal of the current proposal is to investigate the gut microbiome as a potential mechanism and treatment target for TBI-induced psychiatric impairment. The current research will address the TBI-PH Research Program areas of focus in the following fashion: 1a. Understand: Understanding of risk, protective, and biological factors contributing to an individual’s vulnerability to, response to, and long-term outcomes psychological health conditions and/or TBI. 3a Treat: Interventions that promote sustained functional recovery, including interventions administered acutely, during the post-acute phase, or during the chronic phase of injury. To do this, we will undertake an approach in which we administer a pro- or pre-biotic diet before and after injury to promote gut health and prevent bacterial dysfunction. We will then reassess the rats on a battery of psychiatric measures, including our gambling task. We will also collect fecal samples to measure gut microbiome function, blood samples to explore how metabolism is affected, and ultimately brain samples to better understand pathological changes. In a second aim, we will take the fecal samples collected from TBI rats and transplant them into germ-free mice. This will allow us to isolate the gut microbiome and explore how it remodels the gut, brain, and behavior. These mice will have their gut microbiomes sampled and undergo metagenomic shotgun sequencing, a method to provide a much deeper understanding of the gut than is typically feasible in most studies. We anticipate to conduct these studies over a 2-year period. From the findings of this, novel therapeutic interventions could be developed and integrated into military food supply programs (e.g., MREs, cafeterias). Ultimately, these studies will deepen our understanding of the mechanisms by which TBI causes impaired decision-making and may lead to therapeutic breakthroughs for a condition that has no treatments.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310538
Entities
People
- Kris Martens
Organizations
- Ohio State University
- United States Army