Exploring the relationship between the gut microbiome and mental health outcomes in a posttraumatic stress disorder cohort relative to trauma-exposed controls

Study information

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-3-25

study design

case-control

Citation

PMID PubMed identifier for scientific articles.

34923209

DOI Digital object identifier for electronic documents.

10.1016/j.euroneuro.2021.11.009

URI

Authors

Malan-Muller S, Valles-Colomer M, Foxx CL, Vieira-Silva S, van den Heuvel LL, Raes J, Seedat S, Lowry CA, Hemmings SMJ

Journal

European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology

Year

2022

Keywords:

Depression, Gut microbiome, Microbiome-gut-brain axis, Oral microbiome, Posttraumatic stress disorder, Psychotropics

Posttraumatic stress disorder (PTSD) imposes a significant burden on patients and communities. Although the microbiome-gut-brain axis has been proposed as a mediator or moderator of PTSD risk and persistence of symptoms, clinical data directly delineating the gut microbiome's relationship to PTSD are sparse. This study investigated associations between the gut microbiome and mental health outcomes in participants with PTSD (n = 79) and trauma-exposed controls (TECs) (n = 58). Diagnoses of PTSD, major depressive disorder (MDD), and childhood trauma were made using the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), MINI International Neuropsychiatric Interview (MINI), and Childhood Trauma Questionnaire (CTQ), respectively. Microbial communities from stool samples were profiled using 16S ribosomal RNA gene V4 amplicon sequencing and tested for associations with PTSD-related variables of interest. Random forest models identified a consortium of four genera, i.e., a combination of Mitsuokella, Odoribacter, Catenibacterium, and Olsenella, previously associated with periodontal disease, that could distinguish PTSD status with 66.4% accuracy. The relative abundance of this consortium was higher in the PTSD group and correlated positively with CAPS-5 and CTQ scores. MDD diagnosis was also associated with increased relative abundance of the Bacteroidetes phylum. Current use of psychotropics significantly impacted community composition and the relative abundances of several taxa. Early life trauma may prime the microbiome for changes in composition that facilitate a pro-inflammatory cascade and increase the risk of development of PTSD. Future studies should rigorously stratify participants into healthy controls, TECs, and PTSD (stratified by psychotropic drug use) to explore the role of the oral-gut-microbiome-brain axis in trauma-related disorders.

Experiment 1

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Reviewed Marked as Reviewed by ChiomaBlessing on 2024-3-25

Curated date: 2024/03/05

Curator: Keamy

Revision editor(s): Keamy, ChiomaBlessing

Subjects

Location of subjects: South Africa

Host species Species from which microbiome was sampled. Contact us to have more species added.: Homo sapiens

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology: Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Post-traumatic stress disorder ACUTE POST TRAUMATIC STRESS DIS,Acute Post Traumatic Stress Disorder,Acute Post-Traumatic Stress Disorder,CHRONIC POST TRAUMATIC STRESS DIS,Chronic Post Traumatic Stress Disorder,Chronic Post-Traumatic Stress Disorder,combat neurosis,DELAYED ONSET POST TRAUMATIC STRESS DIS,Delayed Onset Post Traumatic Stress Disorder,Delayed Onset Post-Traumatic Stress Disorder,disorder, post-traumatic stress,Neuroses, Post Traumatic,Neuroses, Post-Traumatic,Neuroses, Posttraumatic,POST TRAUMATIC STRESS DIS,Post Traumatic Stress Disorders,Post-Traumatic Neuroses,Post-Traumatic Neurosis,post-traumatic stress disease,post-traumatic stress disorder,Post-Traumatic Stress Disorders,Post-traumatic stress syndrome,Posttraumatic Neuroses,POSTTRAUMATIC STRESS DIS,Posttraumatic stress disorder,Posttraumatic stress disorder (disorder),Posttraumatic stress disorder, NOS,POSTTRAUMATIC STRESS DISORDERS,PTSD,PTSD - Post-traumatic stress disorder,STRESS DIS POST TRAUMATIC,STRESS DIS POSTTRAUMATIC,Stress Disorder, Post Traumatic,Stress Disorder, Post-Traumatic,Stress Disorder, Posttraumatic,Stress Disorders, Post Traumatic,Stress Disorders, Post-Traumatic,Stress Disorders, Posttraumatic,traumatic neurosis,Post-traumatic stress disorder

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Trauma exposed controls (TECs)

Group 1 name Corresponds to the case (exposed) group for case-control studies: Post Traumatic Stress Disorder (PTSD)

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Individuals with Post Traumatic Stress Disorder (PTSD). Post traumatic stress disorder (PTSD) cases met the DSM-5 criteria of PTSD, in accordance with diagnostic evaluation using the Clinician Administered Post Traumatic Stress Disorder Scale for DSM–5 (CAPS-5) and had a CAPS 5 severity score greater than 23.

Group 0 sample size Number of subjects in the control (unexposed) group: 58

Group 1 sample size Number of subjects in the case (exposed) group: 79

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): Antibiotic use within 4 weeks before stool sampling.

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V4

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: relative abundances

Statistical test: Mann-Whitney (Wilcoxon)

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.1

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?: Yes

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment: age, body mass index, sex, Confounders controlled for: "gastrointestinal disease" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.gastrointestinal disease, Confounders controlled for: "unidentified bowel diseases" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.unidentified bowel diseases

Alpha Diversity

Simpson Estimator of species richness and species evenness: more weight on species evenness: unchanged

Experiment 2

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Curated date: 2024/03/06

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Revision editor(s): Keamy, ChiomaBlessing

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Clinical treatment Clinical treatment,clinical treatment

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Individuals not using psychotropic medication

Group 1 name Corresponds to the case (exposed) group for case-control studies: Individuals using psychotropic medication

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Individuals using psychotropic medication that may associate with the gut microbiome of the sample.

Group 0 sample size Number of subjects in the control (unexposed) group: 6

Group 1 sample size Number of subjects in the case (exposed) group: 21

Lab analysis

Statistical Analysis

Statistical test: Linear Regression

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment: age, body mass index, sex, Confounders controlled for: "gastrointestinal diseases" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.gastrointestinal diseases, Confounders controlled for: "unidentified bowel diseases" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.unidentified bowel diseases

Signature 1

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Source: Figure 4A, C and D

Description: Relative abundance (clr-transformed and filtered) of specific taxa at the genus and phylum level in individuals who were using psychotropic medication at the time of sample collection compared to individuals not using psychotropic medication

Abundance in Group 1: increased abundance in Individuals using psychotropic medication

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Bacillota
Bacteroidota
Ruminococcus

Revision editor(s): Keamy, ChiomaBlessing

Signature 2

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Source: Figure 4B and 4E

Description: Relative abundance (clr-transformed and filtered) of specific taxa at the genus and phylum level in individuals who were using psychotropic medication at the time of sample collection compared to individuals not using psychotropic medication

Abundance in Group 1: decreased abundance in Individuals using psychotropic medication

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Akkermansia
Verrucomicrobiota

Revision editor(s): Keamy, ChiomaBlessing

Experiment 3

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Curated date: 2024/03/07

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Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Major depressive disorder major depression,major depressive disorder,recurrent major depression,single major depressive episode,unipolar depression,Major depressive disorder

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Individuals without MDD diagnoses

Group 1 name Corresponds to the case (exposed) group for case-control studies: Individuals with MDD diagnoses

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Individuals diagnosed with Major Depressive Disorder (MDD). The MINI was used to diagnose MDD.

Group 0 sample size Number of subjects in the control (unexposed) group: 2

Group 1 sample size Number of subjects in the case (exposed) group: 20

Lab analysis

Statistical Analysis

Signature 1

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Source: Figure 2

Description: GLM box plot showing relative abundance levels (clr-transformed and filtered) of the phylum Bacteroidetes in individuals who have MDD compared to those who did not have MDD

Abundance in Group 1: increased abundance in Individuals with MDD diagnoses

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Bacteroidota

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