Final report: Does the microbiome play a role in adverse outcomes following mTBI and PTSD?

Department News | June 28, 2022

Through our Small Grants Program launched in 2020, and with support from the Garvey Institute for Brain Health Solutions, we allocated nearly $100,000 to a terrific set of diverse proposals from faculty, staff and trainees on a wide range of topics. Kathleen Pagulayan, PhD, Abigail Schindler, PhD, Rebecca Hendrickson, PhD, and Sean Gibbons, PhD, completed their “Does the microbiome play a role in adverse outcomes following mTBI and PTSD?” project.

The purpose of the study was to conduct a preliminary investigation into the potential association between microbiota abundance, hormone levels, and peripheral inflammation and current symptoms (psychiatric and cognitive) in Veterans with and without a history of mild Traumatic Brain Injury (mTBI). This work has the potential to form a new line of research that could ultimately provide new treatment options for individuals who have treatment-resistant emotional and cognitive difficulties post-mTBI.

Below is their final report

Summary of the work completed
All components of this study were conducted remotely during the COVID-19 pandemic, which presented challenges to participant enrollment and data collection. However, our enrollment target of 50 participants was met in terms of the number of individuals who had consent appointments (i.e., 51 individuals completed phone-based consent appointments and 36 individuals returned signed consent forms via the mail and enrolled in the study). Of the 36 enrolled participants, 15 individuals in the mTBI group and 12 in the control group completed all study procedures, which included at-home sample collection (feces, dried urine, dried blood spots) which was returned to the study via mail as well as the completion of questionnaires via the secure online platform Qualtrics. A medical record review was also conducted by study staff to collect information on TBI history, medical history, and medications on all enrolled participants. Feces was analyzed for microbial abundance and pathway enrichment; neurotransmitter levels were measured in urine; inflammatory, metabolic, and stress-related mediators will be measured in blood. The investigative team has also completed data analysis that has consisted of mixed-factor inferential statistics and machine learning approaches (e.g., principal component analysis, k-means, hierarchical clustering, logistic regression, support vector machine, random forest). As such, we met our intended outcomes for this pilot study.

What did you learn because of this work?
Through this pilot study we were able to learn best practices for conducting microbiome research in a Veteran population. In addition, our research team successfully collected the pilot data described above for future grant applications. Preliminary findings include decreased species diversity (Shannon alpha diversity) and a trend difference in beta diversity in the gut microbiome in Veterans who have a history of blast-related mTBI relative to Veterans with no history of TBI. We also found significant bacterial abundance differences across the groups, and a significant correlation between specific microbial phyla (e.g., Actinobacteria and Verrucomicrobia and Synergistetes) and adverse psychiatric and cognitive outcomes.

What future activities might result from this award?
A manuscript is currently being prepared for publication based the data collected from this pilot study. In addition, a FY21 Traumatic Brain Injury and Psychological Health Research Program (TBIPHRP) Translational Research Award grant proposal was submitted to the Department of Defense (PI: Schindler, Co-Is: Gibbons, Hendrickson, Pagulayan) that built on the findings from the pilot study. That proposal extended this research by focusing on the gut microbiome as a novel prophylactic/treatment target to prevent/treat psychiatric and cognitive symptoms and promote sustained functional recovery following blast-related trauma (e.g., mild traumatic brain injury and/or posttraumatic stress disorder).In addition, our research group plans to submit a NIH and/or VA grant in 2022-2023 that further builds on the findings from this pilot study.