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Microbiome-Gut-Brain Axis Biomarkers for Prevention of Persistent Symptoms-Traumatic Brain Injury(MAPPS-TBI) 

About This Project

Among those who played contact sports (e.g., retired National Football League [NFL] players), lifetime repetitive head impacts and concussions (i.e., mild traumatic brain injury [mTBI]) have been associated with increased risk for adverse brain health and mental health outcomes, including suicide.^1-3 Inflammation resulting from contact sport-related injuries is an underexplored factor that may explain these poor health outcomes. Recent research suggests that gut microbial diversity and microbiome community composition are further negatively impacted after even mTBIs.^4-6

The human microbiota is comprised of 10-100 trillion symbiotic microbial cells (e.g., bacteria, viruses) in and on the human body.⁷ It plays an important role in human health and contributes to physiological functioning.⁸ For example, gut bacteria assist with regulating gut motility and producing vitamins, as well as ensuring that the barrier between the gut and the rest of the body is sufficient. Decreased gut microbial diversity can lead to a leaky gut (i.e., increased intestinal permeability), in which harmful microorganisms or toxins can enter the bloodstream.⁹ Research suggests that living in modern urban settings results in fewer opportunities for microbial exposure to microorganisms, such as bacteria, and consequent decreases in microbial diversity in and on the human body (e.g., within the gut microbiome). Less microbial diversity and an overabundance of specific bacteria have been associated with poor health outcomes.¹⁰ Moreover, the proposed work is predicated on the following assertion. Decreased microbial diversity leads to: failing immunoregulation (regulation of the immune system); increased intestinal permeability; chronic low-grade inflammation; and negative health-related outcomes (e.g., psychiatric conditions; see Figure). As such, most individuals with a history of playing in the NFL are likely to live with a less diverse microbiota and associated compromised immunoregulatory function, as well as increased inflammation. Specifically, this failure of immunoregulation is thought to result in inappropriate inflammation after exposure to repetitive head impacts and concussions, leading to poorer brain health-related outcomes. A more thorough understanding of the role of the gut microbiome in recovery post-mild TBI is vital to developing future interventions to prevent and mitigate symptoms associated with poor brain health among those with a history of TBI. Members of this team have already shown that the use of a specific probiotic (Lactobacillus reuteri DSM 17938) can decrease inflammation in those with a history of mTBI and posttraumatic stress disorder (PTSD).¹¹ To generate new knowledge regarding potential “good and bad bugs” that could be used to help prevent and treat injury-related symptoms, this team will leverage existing longitudinal human gut microbiome samples. In specific, we will map key bacterial biomarkers related to brain and mental and physical health. Findings are expected to lay the groundwork for developing future prevention and intervention strategies.

Project period: 2/1/2024 - 1/31/2026

This study (COMIRB #23-1334) is supported by a grant from the NFL Players Association.

Questions?

Lisa A. Brenner, Principal Investigator, LISA.2.BRENNER@CUANSCHUTZ.EDU

Our Team