Association between gut microbiome composition and symptom self-report in trauma exposed OEF/OIF/OND Veterans

Objective Iraq and Afghanistan war-era (OEF/OIF/OND) Veterans are at elevated risk for physical injuries and psychiatric illnesses, in particular comorbid mild traumatic brain injury (mTBI), posttraumatic stress disorder (PTSD), and chronic pain. The gut microbiome has been implicated in modulation of critical processes such as digestion, immune system functioning, and stress responsivity, and may be an important factor in understanding physical and mental health outcomes following deployment and trauma exposure, yet minimal research to date has sought to characterize gut microbiome composition in this population. Methods 26 male OEF/OIF/OND Veterans aged 18 to 65 who previously completed a VA Comprehensive TBI Evaluation were enrolled in this study. Participants completed self-report measures of PTSD symptom severity, pain intensity and interference, fatigue, cognitive symptoms, substance use, and sleep quality. Participants submitted fecal samples, and metagenomic sequencing was used to calculate alpha- and beta-diversity and taxonomic microbial composition. Associations between microbiome data and clinical variables was then examined. Results Alpha and beta diversity measures were not significantly correlated with clinical outcomes. Fatigue, post-concussive symptoms, executive function symptoms, and cannabis use were associated with differences in gut microbial composition, specifically Verrucomicrobiota. Conclusion This exploratory study demonstrated that altered gut microbiome composition is associated with psychiatric and cognitive symptoms in OEF/OIF/OND Veterans and highlights a potential new therapeutic target of interest. Future research is needed to examine whether probiotic treatment is effective for reducing symptoms common in this clinical population. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by grants from the Department of Veteran Affairs (VA) Basic Laboratory Research and Development (BLR&D) Career Development Award 1IK2BX003258 (AGS), Department of Veteran Affairs VISN 20 MIRECC (AGS, KP, RH, HR), University of Washington Garvey Institute (AGS, KP, RH) ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the Veterans Affairs Puget Sound Health Care System Institutional Review Board. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors