Traumatic Brain Injury (TBI) is a major health problem in the US. It is estimated that over 3 million people live with disabilities caused by TBI with many suffering from disorders including depression or anxiety. The goal of this research proposal is to elucidate how TBI affects the function of peripheral systems and alters the microbiome and the resultant impact on TBI-induced affective disorders. Our preliminary data indicate that CCI causes a rapid shift in microbiota diversity within 24h of TBI, including a dramatic change in the diversity of the psychoactive Lactobacillus family. Based on our data, we are testing the hypothesis that changes to commensal gut microbiota after TBI modulates brain inflammation and drives the development of affective disorder phenotypes in mice. Using 16S rRNA gene sequencing analysis, we will look for differentially abundant taxa, comparing sham to TBI mice. We will also examine if these changes are altered by injury severity, and we will study the impact of sex on the outcome. To test our hypothesis, we will: 1) identify differentially abundant bacteria before and after mild and severe control cortical impact by 16S and metagenomics analysis; 2) perform rescue experiments with probiotics containing TBI-impacted bacteria to study the progression of neuroinflammation process, neuronal death, and neurobehavioral abnormalities; and 3) compare the recovery of germ-free mice exposed to TBI following either sham or TBI mouse fecal transplants. This project will help to further elucidate the gut-brain axis cross-talk and clarify the role of the microbiome on recovery from TBI. Specifically, this project will explore if fecal transplants alter brain function and represent a potential novel therapeutic avenue for TBI. In summary, this research is based on the scientific premise that bacterial within the gut and bacterial diversity can impact behavior, and that brain injury can disrupt diversity in a healthy gut microbiome. !

Public Health Relevance

Communication between the brain and the gut is intriguingly modulated by the microbiome. Gut microbiota have been shown to impact brain inflammation and outcome after brain damage. In this project, our goal is to elucidate which bacteria are altered after traumatic brain injury (TBI), specifically to investigate damage severity in a gender-specific manner. We also will explore TBI treatments based on probiotics that could facilitate the restoration of the intestinal flora after a brain injury to promote recovery from both neuropathological outcomes and anxiety- and depressive-like behaviors. Thus, through understanding the role of specific bacteria in the gut-brain axis, our goal in this project is to identify probiotics that provide immediate benefits to patients suffering from TBI. !

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Exploratory/Developmental Grants (R21)
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Brain Injury and Neurovascular Pathologies Study Section (BINP)
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Bellgowan, Patrick S F
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Methodist Hospital Research Institute
United States
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