Association between microbiome and the development of adverse posttraumatic neuropsychiatric sequelae after traumatic stress exposure
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Published:2023-11-18
Issue:1
Volume:13
Page:
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ISSN:2158-3188
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Container-title:Translational Psychiatry
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language:en
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Short-container-title:Transl Psychiatry
Author:
Zeamer Abigail L.ORCID, Salive Marie-Claire, An Xinming, Beaudoin Francesca L., House Stacey L., Stevens Jennifer S.ORCID, Zeng Donglin, Neylan Thomas C.ORCID, Clifford Gari D., Linnstaedt Sarah D.ORCID, Rauch Scott L., Storrow Alan B.ORCID, Lewandowski ChristopherORCID, Musey Paul I., Hendry Phyllis L., Sheikh SophiaORCID, Jones Christopher W., Punches Brittany E.ORCID, Swor Robert A., Hudak Lauren A., Pascual Jose L.ORCID, Seamon Mark J., Harris Erica, Pearson Claire, Peak David A., Merchant Roland C., Domeier Robert M., Rathlev Niels K., O’Neil Brian J., Sergot Paulina, Sanchez Leon D.ORCID, Bruce Steven E.ORCID, Kessler Ronald C.ORCID, Koenen Karestan C.ORCID, McLean Samuel A.ORCID, Bucci VanniORCID, Haran John P.ORCID
Abstract
AbstractPatients exposed to trauma often experience high rates of adverse post-traumatic neuropsychiatric sequelae (APNS). The biological 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 after trauma exposure has been poorly examined regarding neuropsychiatric outcomes. We aimed to determine whether the gut microbiomes of trauma-exposed emergency department patients who develop APNS have dysfunctional gut microbiome profiles and discover potential associated mechanisms. 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. Two-, eight- and 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 encoded metabolic pathways from stool metagenomics. Microbial species, including Flavonifractor plautii, Ruminococcus gnavus and, Bifidobacterium species, which are prevalent commensal gut microbes, were found to be important in predicting worse APNS outcomes from microbial abundance data. Notably, through APNS outcome modeling using microbial metabolic pathways, worse APNS outcomes were highly predicted by decreased L-arginine related pathway genes and increased citrulline and ornithine pathways. Common commensal microbial species are enriched in individuals who develop APNS. More notably, we identified a biological mechanism through which the gut microbiome reduces global arginine bioavailability, a metabolic change that has also been demonstrated in the plasma of patients with PTSD.
Publisher
Springer Science and Business Media LLC
Subject
Biological Psychiatry,Cellular and Molecular Neuroscience,Psychiatry and Mental health
Reference96 articles.
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