Metagenome-wide association of gut microbiome features for schizophrenia

From BugSigDB
Reviewed Marked as Reviewed by Atrayees on 2023-7-20
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
Authors
Zhu F, Ju Y, Wang W, Wang Q, Guo R, Ma Q, Sun Q, Fan Y, Xie Y, Yang Z, Jie Z, Zhao B, Xiao L, Yang L, Zhang T, Feng J, Guo L, He X, Chen Y, Chen C, Gao C, Xu X, Yang H, Wang J, Dang Y, Madsen L, Brix S, Kristiansen K, Jia H, Ma X
Journal
Nature communications
Year
2020
Evidence is mounting that the gut-brain axis plays an important role in mental diseases fueling mechanistic investigations to provide a basis for future targeted interventions. However, shotgun metagenomic data from treatment-naïve patients are scarce hampering comprehensive analyses of the complex interaction between the gut microbiota and the brain. Here we explore the fecal microbiome based on 90 medication-free schizophrenia patients and 81 controls and identify a microbial species classifier distinguishing patients from controls with an area under the receiver operating characteristic curve (AUC) of 0.896, and replicate the microbiome-based disease classifier in 45 patients and 45 controls (AUC = 0.765). Functional potentials associated with schizophrenia include differences in short-chain fatty acids synthesis, tryptophan metabolism, and synthesis/degradation of neurotransmitters. Transplantation of a schizophrenia-enriched bacterium, Streptococcus vestibularis, appear to induces deficits in social behaviors, and alters neurotransmitter levels in peripheral tissues in recipient mice. Our findings provide new leads for further investigations in cohort studies and animal models.

Experiment 1


Reviewed Marked as Reviewed by Atrayees on 2023-7-20

Curated date: 2021/09/21

Curator: Titas

Revision editor(s): WikiWorks, Chloe, Titas, Atrayees, Aiyshaaaa

Subjects

Location of subjects
China
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
Schizophrenia [X]Schizophrenia, unspecified,[X]Schizophrenia, unspecified (disorder),Dementia Praecox,Disorder, Schizophrenic,Disorders, Schizophrenic,Other specified types of schizophrenia,Other specified types of schizophrenia, chronic state,Other specified types of schizophrenia, chronic state with acute exacerbation,Other specified types of schizophrenia, in remission,Other specified types of schizophrenia, subchronic state,Other specified types of schizophrenia, subchronic state with acute exacerbation,Other specified types of schizophrenia, unspecified state,SCHIZO NEC-CHR/EXACERB,SCHIZO NEC-SUBCHR/EXACER,SCHIZO NOS-CHR/EXACERB,SCHIZO NOS-SUBCHR/EXACER,schizoaffective disorder,schizophrenia,schizophrenia (disease),Schizophrenia (disorder),SCHIZOPHRENIA NEC-CHR,SCHIZOPHRENIA NEC-REMISS,SCHIZOPHRENIA NEC-SUBCHR,SCHIZOPHRENIA NEC-UNSPEC,Schizophrenia NOS,Schizophrenia NOS (disorder),SCHIZOPHRENIA NOS-UNSPEC,schizophrenia with or without an affective disorder,Schizophrenia, NOS,schizophrenia-1,Schizophrenias,SCHIZOPHRENIC DIS,Schizophrenic Disorder,Schizophrenic Disorders,Schizophrenic disorders (disorder),SCZD,Unspecified schizophrenia,Unspecified schizophrenia (disorder),Unspecified schizophrenia, chronic state with acute exacerbation,Unspecified schizophrenia, subchronic state with acute exacerbation,Unspecified schizophrenia, unspecified state,Schizophrenia
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Healthy controls
Group 1 name Corresponds to the case (exposed) group for case-control studies
Schizophrenic patients (ARSCZ, FESCZ)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Only acutely relapsed schizophrenic (ARSCZ) and first-episode schizophrenic (FESCZ) patients were recruited in this study. The current episode of ARSCZ patients was required to happen in the last three months. ARSCZ patients were free of treatment for at least six months. The current episode of FESCZ patients was required to happen in the last year. FESCZ patients did not take any antipsychotics, or their accumulative dosages of antipsychotics intake were much less than the effective dosage (generally less than 100 mg chlorpromazine equivalents in the last two weeks based on the transformation method).
Group 0 sample size Number of subjects in the control (unexposed) group
81
Group 1 sample size Number of subjects in the case (exposed) group
90
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
30 days

Lab analysis

Sequencing type
WMS
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
Not specified
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)
0.05
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
Yes
Matched on Factors on which subjects have been matched on in a case-control study
diet, demographics, socioeconomic status, alcohol drinking, smoking status

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Richness Number of species
increased

Signature 1

Reviewed Marked as Reviewed by Chloe on 2024-1-3

Curated date: 2021/09/22

Curator: Titas

Revision editor(s): Titas, Atrayees, Chloe

Source: Supplementary Data 5A

Description: Significantly decreased gut mOTU between schizophrenia patients and healthy controls

Abundance in Group 1: decreased abundance in Schizophrenic patients (ARSCZ, FESCZ)

NCBI Quality ControlLinks
Lactobacillus acidophilus
Clostridium perfringens
Phocaeicola plebeius

Revision editor(s): Titas, Atrayees, Chloe

Signature 2

Reviewed Marked as Reviewed by Chloe on 2024-1-3

Curated date: 2021/09/23

Curator: Titas

Revision editor(s): Titas, Chloe

Source: Supplementary Data 5A

Description: Significantly increased gut mOTU between schizophrenia patients and healthy controls

Abundance in Group 1: increased abundance in Schizophrenic patients (ARSCZ, FESCZ)

NCBI Quality ControlLinks
Acidaminococcus intestini
Akkermansia muciniphila
Enterococcus faecium
Limosilactobacillus fermentum
Pseudoflavonifractor capillosus
Streptococcus vestibularis
Veillonella parvula
[Eubacterium] siraeum

Revision editor(s): Titas, Chloe

Experiment 2


Reviewed Marked as Reviewed by Chloe on 2024-1-3

Curated date: 2024/01/03

Curator: Chloe

Revision editor(s): Chloe, Victoria

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Healthy controls at baseline
Group 1 name Corresponds to the case (exposed) group for case-control studies
Schizophrenic patients (38 participant subsample) at baseline
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
38 participants with schizophrenia selected for followup. Only acutely relapsed schizophrenic (ARSCZ) and first-episode schizophrenic (FESCZ) patients were recruited in this study. The current episode of ARSCZ patients was required to happen in the last three months. ARSCZ patients were free of treatment for at least six months. The current episode of FESCZ patients was required to happen in the last year. FESCZ patients did not take any antipsychotics, or their accumulative dosages of antipsychotics intake were much less than the effective dosage (generally less than 100 mg chlorpromazine equivalents in the last two weeks based on the transformation method).
Group 1 sample size Number of subjects in the case (exposed) group
38

Lab analysis

Statistical Analysis

Matched on Factors on which subjects have been matched on in a case-control study
alcohol drinking, diet, demographics, smoking status, socioeconomic status


Signature 1

Reviewed Marked as Reviewed by Chloe on 2024-1-3

Curated date: 2024/01/03

Curator: Chloe

Revision editor(s): Chloe

Source: Supplementary Data 10

Description: Taxa decreased in schizophrenic subsample compared to healthy controls

Abundance in Group 1: decreased abundance in Schizophrenic patients (38 participant subsample) at baseline

NCBI Quality ControlLinks
[Eubacterium] siraeum

Revision editor(s): Chloe

Experiment 3


Reviewed Marked as Reviewed by Chloe on 2024-1-3

Curated date: 2024/01/03

Curator: Chloe

Revision editor(s): Chloe, Victoria

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Baseline Healthy controls
Group 1 name Corresponds to the case (exposed) group for case-control studies
3 Month Follow-up Schizophrenic patients (38 participant subsample)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
38 participants with schizophrenia selected for followup at 3 months. Only acutely relapsed schizophrenic (ARSCZ) and first-episode schizophrenic (FESCZ) patients were recruited in this study. The current episode of ARSCZ patients was required to happen in the last three months. ARSCZ patients were free of treatment for at least six months. The current episode of FESCZ patients was required to happen in the last year. FESCZ patients did not take any antipsychotics, or their accumulative dosages of antipsychotics intake were much less than the effective dosage (generally less than 100 mg chlorpromazine equivalents in the last two weeks based on the transformation method).

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by Chloe on 2024-1-3

Curated date: 2024/01/03

Curator: Chloe

Revision editor(s): Chloe

Source: Supplementary Data 10

Description: Baseline healthy controls compared to 3 month Follow up schizophrenia (38 samples)

Abundance in Group 1: increased abundance in 3 Month Follow-up Schizophrenic patients (38 participant subsample)

NCBI Quality ControlLinks
Caulobacter segnis
Caulobacter vibrioides
Peptostreptococcus stomatis
Klebsiella aerogenes
[Bacteroides] pectinophilus
[Eubacterium] siraeum
Klebsiella variicola
Akkermansia muciniphila
Enterobacter hormaechei
Enterobacter cloacae
Alistipes shahii
Enterobacter cancerogenus
Odoribacter splanchnicus
Phocaeicola plebeius

Revision editor(s): Chloe

Signature 2

Reviewed Marked as Reviewed by Chloe on 2024-1-3

Curated date: 2024/01/03

Curator: Chloe

Revision editor(s): Chloe

Source: Supplementary Data 10

Description: Decreased in participants with schizophrenia at 3 months compared to baseline controls

Abundance in Group 1: decreased abundance in 3 Month Follow-up Schizophrenic patients (38 participant subsample)

NCBI Quality ControlLinks
butyrate-producing bacterium
Ruminococcus sp. 5_1_39BFAA
butyrate-producing bacterium SS3/4

Revision editor(s): Chloe

Experiment 4


Reviewed Marked as Reviewed by ChiomaBlessing on 2023-12-27

Curated date: 2024/01/03

Curator: Chloe

Revision editor(s): Chloe, Victoria

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Antipsychotic drug antipsychotic,antipsychotic agents,antipsychotic drugs,antipsychotics,antipsychotiques,grosser Tranquilizer,major tranquilizers,major tranquilizing agents,neuroleptic,neuroleptic agents,neuroleptics,Neuroleptikum,neuroleptique,neuroleptiques,Antipsychotic drug,antipsychotic drug
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Baseline Schizophrenic patients (38 participant subsample)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Alterations in abundance of mOTUs in the gut of SCZ patients after 3-month antipsychotics treatment
Group 0 sample size Number of subjects in the control (unexposed) group
38

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by ChiomaBlessing on 2023-12-27

Curated date: 2024/01/03

Curator: Chloe

Revision editor(s): Chloe

Source: Supplementary Data 11

Description: Increased in 3 month follow-up schizophrenia patients treated with antipsychotics compared to baseline

Abundance in Group 1: increased abundance in 3 Month Follow-up Schizophrenic patients (38 participant subsample)

NCBI Quality ControlLinks
Enterobacter cloacae
Klebsiella aerogenes

Revision editor(s): Chloe