Authors

Abigail L. Zeamer, University of Massachusetts Chan Medical School
Marie Claire Salive, University of Massachusetts Chan Medical School
Xinming An, The University of North Carolina at Chapel Hill
Francesca L. Beaudoin, Brown University
Stacey L. House, Washington University School of Medicine in St. Louis
Jennifer S. Stevens, Emory University School of Medicine
Donglin Zeng, UNC Gillings School of Global Public Health
Thomas C. Neylan, University of California, San Francisco
Gari D. Clifford, Emory University School of Medicine
Sarah D. Linnstaedt, The University of North Carolina at Chapel Hill
Scott L. Rauch, Harvard Medical School
Alan B. Storrow, Vanderbilt University Medical Center
Christopher Lewandowski, Henry Ford Health System
Paul I. Musey, Indiana University School of Medicine
Phyllis L. Hendry, University of Florida College of Medicine
Sophia Sheikh, University of Florida College of Medicine
Christopher W. Jones, Cooper Medical School of Rowan University
Brittany E. Punches, The Ohio State University College of Medicine
Robert A. Swor, Oakland University William Beaumont School of Medicine
Lauren A. Hudak, Emory University School of Medicine
Jose L. Pascual, University of Pennsylvania
Mark J. Seamon, University of Pennsylvania
Erica Harris, Albert Einstein Healthcare Network
Claire Pearson, Wayne State University
David A. Peak, Massachusetts General Hospital
Roland C. Merchant, Brigham and Women's Hospital
Robert M. Domeier, Trinity Health - Novi
Niels K. Rathlev, UMass Chan Medical School - Baystate
Brian J. O’Neil, Wayne State University
Paulina Sergot, McGovern Medical School
Leon D. Sanchez, Brigham and Women's Hospital
Steven E. Bruce, University of Missouri-St. Louis

Document Type

Article

Abstract

Patients 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.

Publication Date

12-1-2023

Volume

13

Issue

1

First Page

National Institutes of Health

DOI

10.1038/s41398-023-02643-8

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Repository URL

https://irl.umsl.edu/psychology-faculty/116