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Background Patients exposed to trauma often experience high rates of adverse post-traumatic neuropsychiatric sequelae (APNS). The biologic mechanisms promoting APNS are currently unknown, but the microbiota-gut-brain axis offers an avenue to understanding mechanisms as well as possibilities for intervention. Microbiome composition at the time of trauma exposure has been poorly examined regarding neuropsychiatric outcomes. We aimed to determine whether baseline the gut microbiomes of trauma-exposed emergency department patients who later develop APNS have dysfunctional gut microbiome profiles and discover potential 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 traumA (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 created for each outcome using microbial abundances and relevant demographics. Mixed-effect random forest machine learning models were used to identify associations between APNS outcomes and microbial features and metabolic pathways.

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 APNS outcomes. Notably, worse APNS outcomes were highly predicted by decreased L-arginine related pathway genes and increased citrulline and ornithine pathways.

Conclusions 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 also has been demonstrated in patients with PTSD.