Association between microbiome and the development of adverse posttraumatic neuropsychiatric sequelae after traumatic stress exposure
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 inte...
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-11-01
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| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-023-02643-8 |
| _version_ | 1827708209402478592 |
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| author | 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 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 |
| author_facet | 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 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 |
| author_sort | Abigail L. Zeamer |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T17:00:27Z |
| format | Article |
| id | doaj.art-fb57c63b495e44c08b1765a3bb2c473b |
| institution | Directory Open Access Journal |
| issn | 2158-3188 |
| language | English |
| last_indexed | 2024-03-10T17:00:27Z |
| publishDate | 2023-11-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj.art-fb57c63b495e44c08b1765a3bb2c473b2023-11-20T11:00:27ZengNature Publishing GroupTranslational Psychiatry2158-31882023-11-0113111410.1038/s41398-023-02643-8Association between microbiome and the development of adverse posttraumatic neuropsychiatric sequelae after traumatic stress exposureAbigail L. Zeamer0Marie-Claire Salive1Xinming An2Francesca L. Beaudoin3Stacey L. House4Jennifer S. Stevens5Donglin Zeng6Thomas C. Neylan7Gari D. Clifford8Sarah D. Linnstaedt9Scott L. Rauch10Alan B. Storrow11Christopher Lewandowski12Paul I. Musey13Phyllis L. Hendry14Sophia Sheikh15Christopher W. Jones16Brittany E. Punches17Robert A. Swor18Lauren A. Hudak19Jose L. Pascual20Mark J. Seamon21Erica Harris22Claire Pearson23David A. Peak24Roland C. Merchant25Robert M. Domeier26Niels K. Rathlev27Brian J. O’Neil28Paulina Sergot29Leon D. Sanchez30Steven E. Bruce31Ronald C. Kessler32Karestan C. Koenen33Samuel A. McLean34Vanni Bucci35John P. Haran36Department of Microbiology and Physiologic Systems, University of Massachusetts Chan Medical SchoolDepartment of Emergency Medicine, University of Massachusetts Chan Medical SchoolInstitute for Trauma Recovery, University of North Carolina at Chapel HillDepartment of Epidemiology, Brown UniversityDepartment of Emergency Medicine, Washington University School of MedicineDepartment of Psychiatry and Behavioral Sciences, Emory University School of MedicineDepartment of Biostatistics, Gillings School of Global Public Health, University of North CarolinaDepartments of Psychiatry and Neurology, University of California San FranciscoDepartment of Biomedical Informatics, Emory University School of MedicineInstitute for Trauma Recovery, University of North Carolina at Chapel HillDepartment of Psychiatry, Harvard Medical SchoolDepartment of Emergency Medicine, Vanderbilt University Medical CenterDepartment of Emergency Medicine, Henry Ford Health SystemDepartment of Emergency Medicine, Indiana University School of MedicineDepartment of Emergency Medicine, University of Florida College of Medicine-JacksonvilleDepartment of Emergency Medicine, University of Florida College of Medicine-JacksonvilleDepartment of Emergency Medicine, Cooper Medical School of Rowan UniversityDepartment of Emergency Medicine, Ohio State University College of MedicineDepartment of Emergency Medicine, Oakland University William Beaumont School of MedicineDepartment of Emergency Medicine, Emory University School of MedicineDepartment of Surgery, University of PennsylvaniaDepartment of Surgery, University of PennsylvaniaDepartment of Emergency Medicine, Einstein Medical CenterDepartment of Emergency Medicine, Wayne State University, Ascension St. John HospitalDepartment of Emergency Medicine, Massachusetts General HospitalDepartment of Emergency Medicine, Brigham and Women’s HospitalDepartment of Emergency Medicine, Trinity Health-Ann ArborDepartment of Emergency Medicine, University of Massachusetts Medical School-BaystateDepartment of Emergency Medicine, Wayne State University, Detroit Receiving HospitalDepartment of Emergency Medicine, McGovern Medical School at UTHealthDepartment of Emergency Medicine, Brigham and Women’s HospitalDepartment of Psychological Sciences, University of Missouri - St. LouisDepartment of Health Care Policy, Harvard Medical SchoolDepartment of Epidemiology, Harvard UniversityDepartment of Emergency Medicine, University of North Carolina at Chapel HillDepartment of Microbiology and Physiologic Systems, University of Massachusetts Chan Medical SchoolDepartment of Microbiology and Physiologic Systems, University of Massachusetts Chan Medical SchoolAbstract 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.https://doi.org/10.1038/s41398-023-02643-8 |
| spellingShingle | 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 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 Association between microbiome and the development of adverse posttraumatic neuropsychiatric sequelae after traumatic stress exposure Translational Psychiatry |
| title | Association between microbiome and the development of adverse posttraumatic neuropsychiatric sequelae after traumatic stress exposure |
| title_full | Association between microbiome and the development of adverse posttraumatic neuropsychiatric sequelae after traumatic stress exposure |
| title_fullStr | Association between microbiome and the development of adverse posttraumatic neuropsychiatric sequelae after traumatic stress exposure |
| title_full_unstemmed | Association between microbiome and the development of adverse posttraumatic neuropsychiatric sequelae after traumatic stress exposure |
| title_short | Association between microbiome and the development of adverse posttraumatic neuropsychiatric sequelae after traumatic stress exposure |
| title_sort | association between microbiome and the development of adverse posttraumatic neuropsychiatric sequelae after traumatic stress exposure |
| url | https://doi.org/10.1038/s41398-023-02643-8 |
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