Association between microbiome and the development of adverse posttraumatic neuropsychiatric sequelae after traumatic stress exposure

• Type of Material: Article
• Authors: Abigail L. Zeamer, University of Massachusetts, Worcester; Marie-Claire Salive, University of Massachusetts, Worcester; Xinming An, University of North Carolina, Chapel Hill; Francesca L. Beaudoin, Brown University; Stacey L. House, Washington University, St. Louis; Jennifer Stevens, Emory University; Donglin Zeng, University of North Carolina, Chapel Hill; Thomas C. Neylan, University of California, San Francisco; Gari D. Clifford, Emory University; Srah D. Linnstaedt, University of North Carolina, Chapel Hill; Scott L. Rauch, Harvard University; Alan B. Storrow, Vanderbilt University; Christopher Lewandowski, Henry Ford Health System; Paul I. Musey Jr., Indiana University, Indianapolis; Phyllis L. Hendry, University of Florida, Jacksonville; Sophia Sheikh, University of Florida, Jacksonville; Christopher W. Jones, Rowan University; Brittany E. Punches, Ohio State University; Robert A. Swor, Oakland University; Lauren A. Hudak, Emory University; Jose L. Pascual, University of Pennsylvania; Mark J. Seamon, University of Pennsylvania; erica Harris, Einstein Medical Center; Claire Pearson, Wayne State University; David A. Peak, Massachusetts General Hospital; Roland C. Merchant, Brigham and Women's Hospital; Robert M. Domeier, Trinity Health, Ann Arbor; Niels K. Rathlev, University of Massachusetts, Springfield; Brian J. O'Neil, Wayne State University; Paulina Sergot, University of Texas, Houston; Leon D. Sanchez, Harvard University; Steven E. Bruce, University of Missouri, St. Louis; ronald C. Kessler, Harvard University; Karestan C. Koenen, Harvard University; Samuel A. McLean, University of North Carolina, Chapel Hill; Vanni Bucci, University of Massachusetts, Worcester; John P. Haran, University of Massachusetts, Worcester
• Language: English
• Date: 2023-11-18
• Publisher: Springer Nature
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2023
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): https://doi.org/10.1038/s41398-023-02643-8
• Title of Journal or Parent Work: Translational Psychiatry
• Volume: 13
• Start Page: 354
• Grant/Funding Information: The AURORA (parent) study was supported by NIMH under U01MH110925, the US Army MRMC, One Mind, and The Mayday Fund. The content is solely responsibility of the authors and does not necessarily represent the official views of any of the funders. Data and/or research tools used in the preparation of this manuscript were obtained from the National Institute of Mental Health (NIMH) Data Archive (NDA). NDA is a collaborative informatics system created by the National Institutes of Health to provide a national resource to support and accelerate research in mental health. Dataset identifier(s): NIMH Data Archive Digital Object Identifier (DOI) 10.15154/1528593.; This work was supported by R01 AG067483-01 to J.H. and by the CDMRP PRMP W81XWH2020013 to V.B.
• Keywords: Human behaviour; Depression
• Research Categories: Biology, Neuroscience; Psychology, Psychobiology

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.