Metagenome-wide association of gut microbiome features for schizophrenia
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Study information
-
Quality control
- Retracted paper
- Contamination issues suspected
- Batch effect issues suspected
- Uncontrolled confounding suspected
- Results are suspect (various reasons)
- Tags applied
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
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
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 Control | Links |
|---|---|---|
| Lactobacillus acidophilus | ||
| Clostridium perfringens | ||
| Phocaeicola plebeius |
Signature 2
Reviewed Marked as Reviewed by Chloe on 2024-1-3
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)
Experiment 2
Reviewed Marked as Reviewed by Chloe on 2024-1-3
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
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- Not specified
- 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
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 Control | Links |
|---|---|---|
| [Eubacterium] siraeum |
Revision editor(s): Chloe
Experiment 3
Reviewed Marked as Reviewed by Chloe on 2024-1-3
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
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)
Revision editor(s): Chloe
Signature 2
Reviewed Marked as Reviewed by Chloe on 2024-1-3
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 Control | Links |
|---|---|---|
| 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
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
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 Control | Links |
|---|---|---|
| Enterobacter cloacae | ||
| Klebsiella aerogenes |
Revision editor(s): Chloe
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