Pilot study of the association between microbiome characteristics and the development of adverse posttraumatic neuropsychiatric sequelae after traumatic stress exposure

Background: Patients suffering trauma often experience high rates of post-traumatic neuropsychiatric sequelae (APNS). The biologic mechanisms promoting APNS are currently unknown, but the microbiota-gut-brain axis offers both an avenue to understanding mechanism as well as possibilities for intervention. Microbiome composition at the time of trauma exposure has been poorly examined with regards to neuropsychiatric outcomes. This study aims to determine whether the gut microbiomes of trauma exposed ED patients who go on to suffer APNS have dysfunctional profiles and discover potential microbiome associated mechanisms.Methods: We performed metagenomic analysis on stool samples (n=51) from a subset of adults enrolled in the Advancing Understanding of RecOvery afteR traumaA (AURORA) study. Twelve-week post-trauma outcomes for post-traumatic stress disorder (PTSD) (PTSD checklist for DSM-5), normalized depression scores (PROMIS Depression Short Form 8b) and somatic symptom counts were collected. Generalized linear models were fit to each outcome with microbial abundances and relevant demographics. Mixed-effect random forest machine learning models were used to identify associations between microbial features and metabolic pathways with outcomes.Results: Microbial species including Flavonifactor plautti and Ruminococcus gnavus, which are associated with inflammation and poor health outcomes, were found to be important in predicting worse outcomes. Notably, worse outcomes were highly predicted by decreased L-arginine related pathway genes and increased citrulline and ornithine pathways.Conclusions: We identified pro-inflammatory microbes that are enriched in individuals who develop APNS. More notably, we identified a biological mechanism through which the gut microbiome reduces global arginine bioavailability, which has been demonstrated in PTSD patients.