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

Abigail L Zeamer; Marie-Claire Salive; Xinming An; Francesca L Beaudoin; Stacey L House; Jennifer S Stevens; Donglin Zeng; Thomas C Neylan; Gari D Clifford; Sarah D Linnstaedt; Scott L Rauch; Alan B Storrow; Christopher Lewandowski; Paul I Musey Jr; Phyllis L Hendry; Sophia Sheikh; Christopher W Jones; Brittany E Punches; Robert A Swor; Lauren A Hudak; Jose L Pascual; Mark J Seamon; Erica Harris; Claire Pearson; David A Peak; Roland C Merchant; Robert M Domeier; Niels K Rathlev; Brian J O'Neil; Paulina Sergot; Leon D Sanchez; Steven E Bruce; Ronald C Kessler; Karestan C Koenen; Samuel A McLean; Vanni Bucci; John P Haran

doi:10.1038/s41398-023-02643-8

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

Transl Psychiatry. 2023 Nov 18;13(1):354. doi: 10.1038/s41398-023-02643-8.

Authors

Abigail L Zeamer¹, Marie-Claire Salive², Xinming An³, Francesca L Beaudoin^{4

5}, Stacey L House⁶, Jennifer S Stevens⁷, Donglin Zeng⁸, Thomas C Neylan⁹, Gari D Clifford^{10

11}, Sarah D Linnstaedt^{3

12

13}, Scott L Rauch^{13

14

15}, Alan B Storrow¹⁶, Christopher Lewandowski¹⁷, Paul I Musey Jr¹⁸, Phyllis L Hendry¹⁹, Sophia Sheikh¹⁹, Christopher W Jones²⁰, Brittany E Punches^{21

22}, Robert A Swor²³, Lauren A Hudak²⁴, Jose L Pascual^{25

26}, Mark J Seamon^{25

26}, Erica Harris²⁷, Claire Pearson²⁸, David A Peak²⁹, Roland C Merchant³⁰, Robert M Domeier³¹, Niels K Rathlev³², Brian J O'Neil³³, Paulina Sergot³⁴, Leon D Sanchez^{30

35}, Steven E Bruce³⁶, Ronald C Kessler³⁷, Karestan C Koenen³⁸, Samuel A McLean³⁹, Vanni Bucci^{40

41}, John P Haran^{42

43

44}

Affiliations

¹ Department of Microbiology and Physiologic Systems, University of Massachusetts Chan Medical School, Worcester, MA, USA.
² Department of Emergency Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
³ Institute for Trauma Recovery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁴ Department of Epidemiology, Brown University, Providence, RI, USA.
⁵ Department of Emergency Medicine, Brown University, Providence, RI, USA.
⁶ Department of Emergency Medicine, Washington University School of Medicine, St. Louis, MO, USA.
⁷ Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
⁸ Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.
⁹ Departments of Psychiatry and Neurology, University of California San Francisco, San Francisco, CA, USA.
¹⁰ Department of Biomedical Informatics, Emory University School of Medicine, Atlanta, GA, USA.
¹¹ Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA.
¹² The Many Brains Project, Belmont, MA, USA.
¹³ Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
¹⁴ Institute for Technology in Psychiatry, McLean Hospital, Belmont, MA, USA.
¹⁵ Department of Psychiatry, McLean Hospital, Belmont, MA, USA.
¹⁶ Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
¹⁷ Department of Emergency Medicine, Henry Ford Health System, Detroit, MI, USA.
¹⁸ Department of Emergency Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
¹⁹ Department of Emergency Medicine, University of Florida College of Medicine-Jacksonville, Jacksonville, FL, USA.
²⁰ Department of Emergency Medicine, Cooper Medical School of Rowan University, Camden, NJ, USA.
²¹ Department of Emergency Medicine, Ohio State University College of Medicine, Columbus, OH, USA.
²² Ohio State University College of Nursing, Columbus, OH, USA.
²³ Department of Emergency Medicine, Oakland University William Beaumont School of Medicine, Rochester, MI, USA.
²⁴ Department of Emergency Medicine, Emory University School of Medicine, Atlanta, GA, USA.
²⁵ Department of Surgery, University of Pennsylvania, Philadelphia, PA, USA.
²⁶ Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
²⁷ Department of Emergency Medicine, Einstein Medical Center, Philadelphia, PA, USA.
²⁸ Department of Emergency Medicine, Wayne State University, Ascension St. John Hospital, Detroit, MI, USA.
²⁹ Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA, USA.
³⁰ Department of Emergency Medicine, Brigham and Women's Hospital, Boston, MA, USA.
³¹ Department of Emergency Medicine, Trinity Health-Ann Arbor, Ypsilanti, MI, USA.
³² Department of Emergency Medicine, University of Massachusetts Medical School-Baystate, Springfield, MA, USA.
³³ Department of Emergency Medicine, Wayne State University, Detroit Receiving Hospital, Detroit, MI, USA.
³⁴ Department of Emergency Medicine, McGovern Medical School at UTHealth, Houston, TX, USA.
³⁵ Department of Emergency Medicine, Harvard Medical School, Boston, MA, USA.
³⁶ Department of Psychological Sciences, University of Missouri - St. Louis, St. Louis, MO, USA.
³⁷ Department of Health Care Policy, Harvard Medical School, Boston, MA, USA.
³⁸ Department of Epidemiology, Harvard University, Boston, MA, USA.
³⁹ Department of Emergency Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁴⁰ Department of Microbiology and Physiologic Systems, University of Massachusetts Chan Medical School, Worcester, MA, USA. vanni.bucci@umassmed.edu.
⁴¹ Program in Microbiome Dynamics, University of Massachusetts Chan Medical School, Worcester, MA, USA. vanni.bucci@umassmed.edu.
⁴² Department of Microbiology and Physiologic Systems, University of Massachusetts Chan Medical School, Worcester, MA, USA. john.haran@umassmed.edu.
⁴³ Department of Emergency Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA. john.haran@umassmed.edu.
⁴⁴ Program in Microbiome Dynamics, University of Massachusetts Chan Medical School, Worcester, MA, USA. john.haran@umassmed.edu.

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.

MeSH terms

Adult
Biological Availability
Feces / microbiology
Gastrointestinal Microbiome*
Humans
Microbiota*
Stress Disorders, Post-Traumatic* / metabolism

Abstract

MeSH terms

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