Transplantation of gut microbiota derived from patients with schizophrenia induces schizophrenia-like behaviors and dysregulated brain transcript response in mice
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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.
URI
Authors
Wei N, Ju M, Su X, Zhang Y, Huang Y, Rao X, Cui L, Lin Z, Dong Y
Journal
Schizophrenia (Heidelberg, Germany)
Year
2024
Schizophrenia (SCZ), as a neurodevelopmental disorder and devastating disease, affects approximately 1% of the world population. Although numerous studies have attempted to elucidate the causes of SCZ occurrence, it is not clearly understood. Recently, the emerging roles of the gut microbiota in a range of brain disorders, including SCZ, have attracted much attention. While the molecular mechanism of gut microbiota in regulating the pathogenesis of SCZ is still lacking. Here, we first confirmed the difference of gut microbiome between SCZ patients and healthy controls, and then, we performed fecal microbiota transplantation (FMT) to clarify the roles of SCZ patients-derived microbiota in a specific pathogen free (SPF) mice model. 16 S rDNA sequencing confirmed that a significant difference of gut microbiome was present between two groups of FMT mice, which has a similar trend with the above human gut microbiome. Furthermore, we found that transplantation of fecal microbiota from SCZ patients into SPF mice was sufficient to induce schizophrenia-like (SCZ-like) symptoms, such as deficits in sociability and hyperactivity. Furthermore, the brains of mice colonized with SCZ microbiota displayed dysregulated transcript response and alternative splicing of SCZ-relevant genes. Moreover, 10 key genes were identified to be correlated with SCZ by an integrative transcriptome data analysis. Finally, 4 key genes were identified to be correlated with the 12 differential genera between two groups of FMT mice. Our results thus demonstrated that the gut microbiome might modify the transcriptomic profile in the brain, thereby modulating social behavior, and our present study can help better understand the link between gut microbiota and SCZ pathogenesis through the gut-brain axis.
Experiment 1
Reviewed Marked as Reviewed by Svetlana up on 2024-7-18
Curated date: 2024/07/03
Curator: Jacob A. De Jesus
Revision editor(s): Jacob A. De Jesus, Scholastica
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
- HCF: healthy controls (no psychiatric diagnosis of schizophrenia)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- SCZF: patients with schizophrenia
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- antipsychotic-treated patients with schizophrenia
- Group 0 sample size Number of subjects in the control (unexposed) group
- 15
- Group 1 sample size Number of subjects in the case (exposed) group
- 20
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- 1 month
Lab analysis
- Sequencing type
- 16S
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- V3-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
- LEfSe
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.05
Alpha Diversity
- Pielou Quantifies how equal the community is numerically
- decreased
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
- Chao1 Abundance-based estimator of species richness
- decreased
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- decreased
- Richness Number of species
- decreased
- Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
- decreased
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2024-7-18
Curated date: 2024/07/10
Curator: Jacob A. De Jesus
Revision editor(s): Jacob A. De Jesus, Scholastica
Source: Figure 2B
Description: LEfSe comparison of gut microbiota in antipsychotic-treated patients with schizophrenia (SCZF group) versus healthy controls (HCF group)
Abundance in Group 1: increased abundance in SCZF: patients with schizophrenia
Revision editor(s): Jacob A. De Jesus, Scholastica
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2024-7-18
Curated date: 2024/07/10
Curator: Jacob A. De Jesus
Revision editor(s): Jacob A. De Jesus, Scholastica
Source: Figure 2B
Description: LEfSe comparison of gut microbiota in antipsychotic-treated patients with schizophrenia (SCZF group) versus healthy controls (HCF group)
Abundance in Group 1: decreased abundance in SCZF: patients with schizophrenia
Revision editor(s): Jacob A. De Jesus, Scholastica
Experiment 2
Reviewed Marked as Reviewed by Svetlana up on 2024-7-18
Curated date: 2024/07/16
Curator: Jacob A. De Jesus
Revision editor(s): Jacob A. De Jesus, Scholastica
Differences from previous experiment shown
Subjects
- Host species Species from which microbiome was sampled. Contact us to have more species added.
- Mus musculus
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- HC: healthy control fecal microbiota-recipient mice
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- SCZ: schizophrenia fecal microbiota-recipient mice
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Male C57BL/6 mice which transplanted fecal microbiota from a human patient with a schizophrenia psychiatric disorder.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 5
- Group 1 sample size Number of subjects in the case (exposed) group
- 5
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- Not specified
Lab analysis
Statistical Analysis
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2024-7-18
Curated date: 2024/07/16
Curator: Jacob A. De Jesus
Revision editor(s): Jacob A. De Jesus, Scholastica
Source: Figure 4D
Description: Bacterial genera differentially expressed in mice transplanted with schizophrenia versus healthy control fecal microbiota
Abundance in Group 1: increased abundance in SCZ: schizophrenia fecal microbiota-recipient mice
Revision editor(s): Jacob A. De Jesus, Scholastica
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2024-7-18
Curated date: 2024/07/16
Curator: Jacob A. De Jesus
Revision editor(s): Jacob A. De Jesus, Scholastica
Source: Figure 4D
Description: Bacterial genera differentially expressed in mice transplanted with schizophrenia versus healthy control fecal microbiota
Abundance in Group 1: decreased abundance in SCZ: schizophrenia fecal microbiota-recipient mice
| NCBI | Quality Control | Links |
|---|---|---|
| Alistipes | ||
| Bacteroides | ||
| Christensenella | ||
| Lactobacillus | ||
| Parabacteroides | ||
| Thomasclavelia |
Revision editor(s): Jacob A. De Jesus, Scholastica
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