Gut Microbiome Alterations Precede Cerebral Amyloidosis and Microglial Pathology in a Mouse Model of Alzheimer's Disease
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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
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Chen Y, Fang L, Chen S, Zhou H, Fan Y, Lin L, Li J, Xu J, Chen Y, Ma Y, Chen Y
Journal
BioMed research international
Year
2020
Emerging evidence suggests that the gut microbiome actively regulates cognitive functions and that gut microbiome imbalance is associated with Alzheimer's disease (AD), the most prevalent neurodegenerative disorder. However, the changes in gut microbiome composition in AD and their association with disease pathology, especially in the early stages, are unclear. Here, we compared the profiles of gut microbiota between APP/PS1 transgenic mice (an AD mouse model) and their wild-type littermates at different ages by amplicon-based sequencing of 16S ribosomal RNA genes. Microbiota composition started diverging between the APP/PS1 and wild-type mice at young ages (i.e., 1-3 months), before obvious amyloid deposition and plaque-localized microglial activation in the cerebral cortex in APP/PS1 mice. At later ages (i.e., 6 and 9 months), there were distinct changes in the abundance of inflammation-related bacterial taxa including Escherichia-Shigella, Desulfovibrio, Akkermansia, and Blautia in APP/PS1 mice. These findings suggest that gut microbiota alterations precede the development of key pathological features of AD, including amyloidosis and plaque-localized neuroinflammation. Thus, the investigation of gut microbiota might provide new avenues for developing diagnostic biomarkers and therapeutic targets for AD.
Experiment 1
Subjects
- Location of subjects
- China
- Host species Species from which microbiome was sampled. Contact us to have more species added.
- Mus musculus
- 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
- Alzheimer's disease [X]Dementia in Alzheimer's disease,[X]Dementia in Alzheimer's disease (disorder),AD,AD - Alzheimer's disease,Alzheimer Dementia,Alzheimer dementia,Alzheimer Dementia, Presenile,ALZHEIMER DIS,Alzheimer Disease,Alzheimer disease,Alzheimer disease, familial,Alzheimer Type Dementia,Alzheimer's,Alzheimer's Dementia,Alzheimer's dementia,Alzheimer's disease,Alzheimer's disease (disorder),Alzheimer's disease, NOS,Alzheimers,Alzheimers Dementia,Alzheimers dementia,ALZHEIMERS DIS,Alzheimers disease,DAT - Dementia Alzheimer's type,Dementia in Alzheimer's disease,Dementia in Alzheimer's disease (disorder),Dementia in Alzheimer's disease, unspecified (disorder),Dementia of the Alzheimer's type,Dementia, Alzheimer Type,Dementia, Presenile,Dementia, Presenile Alzheimer,Disease, Alzheimer,Disease, Alzheimer's,Presenile Alzheimer Dementia,sporadic Alzheimer's disease,alzheimer's disease
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Wild-type (WT)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- APP/PS1
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Alzheimer's Disease (AD) mouse model 1-month-old
- Group 0 sample size Number of subjects in the control (unexposed) group
- 14
- Group 1 sample size Number of subjects in the case (exposed) group
- 21
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
- MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
- No
- LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
- 2.5
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Chao1 Abundance-based estimator of species richness
- unchanged
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- unchanged
- Richness Number of species
- unchanged
Signature 1
Source: Table S2
Description: Significantly different taxa between WT and AD (APP/PS1) mice
Abundance in Group 1: increased abundance in APP/PS1
| NCBI | Quality Control | Links |
|---|---|---|
| Enterobacteriaceae |
Revision editor(s): AaishahM
Experiment 2
Differences from previous experiment shown
Subjects
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Alzheimer's Disease (AD) mouse model 2-month-old
- Group 0 sample size Number of subjects in the control (unexposed) group
- 17
- Group 1 sample size Number of subjects in the case (exposed) group
- 24
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Chao1 Abundance-based estimator of species richness
- increased
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- unchanged
- Richness Number of species
- unchanged
Signature 1
Source: Table S2
Description: Significantly different taxa between WT and AD (APP/PS1) mice
Abundance in Group 1: increased abundance in APP/PS1
| NCBI | Quality Control | Links |
|---|---|---|
| Actinomycetota | ||
| Akkermansia | ||
| Allobaculum | ||
| Alloprevotella | ||
| Bifidobacterium | ||
| Erysipelotrichaceae | ||
| Prevotellaceae | ||
| Verrucomicrobiaceae | ||
| Verrucomicrobiota | ||
| Thomasclavelia |
Revision editor(s): AaishahM
Experiment 3
Differences from previous experiment shown
Subjects
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Alzheimer's Disease (AD) mouse model 3-month-old
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Chao1 Abundance-based estimator of species richness
- unchanged
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- unchanged
- Richness Number of species
- unchanged
Experiment 4
Differences from previous experiment shown
Subjects
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Alzheimer's Disease (AD) mouse model 6-month-old
- Group 0 sample size Number of subjects in the control (unexposed) group
- 31
- Group 1 sample size Number of subjects in the case (exposed) group
- 34
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Chao1 Abundance-based estimator of species richness
- unchanged
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- unchanged
- Richness Number of species
- unchanged
Signature 1
Source: Table S2
Description: Significantly different taxa between WT and AD (APP/PS1) mice
Abundance in Group 1: increased abundance in APP/PS1
Revision editor(s): AaishahM
Signature 2
Source: Table S2
Description: Significantly different taxa between WT and AD (APP/PS1) mice
Abundance in Group 1: decreased abundance in APP/PS1
| NCBI | Quality Control | Links |
|---|---|---|
| Bacteroidaceae | ||
| Bacteroides | ||
| Escherichia/Shigella sp. | ||
| Rikenellaceae | ||
| g_Rikenellaceae_RC9_gut_groupg_Rikenellaceae_RC9_gut_group |
Revision editor(s): AaishahM
Experiment 5
Differences from previous experiment shown
Subjects
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Alzheimer's Disease (AD) mouse model 9-month-old
- Group 0 sample size Number of subjects in the control (unexposed) group
- 18
- Group 1 sample size Number of subjects in the case (exposed) group
- 18
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Chao1 Abundance-based estimator of species richness
- increased
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- unchanged
- Richness Number of species
- increased
Signature 1
Source: Table S2
Description: Significantly different taxa between WT and AD (APP/PS1) mice
Abundance in Group 1: increased abundance in APP/PS1
Revision editor(s): AaishahM
Signature 2
Source: Table S2
Description: Significantly different taxa between WT and AD(APP/PS1) mice
Abundance in Group 1: decreased abundance in APP/PS1
| NCBI | Quality Control | Links |
|---|---|---|
| Alistipes | ||
| Atopostipes | ||
| Carnobacteriaceae | ||
| g_Lachnospiraceae_UCG-006g_Lachnospiraceae_UCG-006 | ||
| g_[Eubacterium]_nodatum_groupg_[Eubacterium]_nodatum_group |
Revision editor(s): AaishahM
Experiment 6
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- A combination of groups WT 2m, 3m, 6m, 9m
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- WT 1m
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Wild-type mouse 1-month-old
- Group 0 sample size Number of subjects in the control (unexposed) group
- 83
- Group 1 sample size Number of subjects in the case (exposed) group
- 14
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Chao1 Abundance-based estimator of species richness
- unchanged
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- unchanged
- Richness Number of species
- unchanged
Signature 1
Source: Figure S3 A
Description: Differentially represented bacterial taxa of WT
Abundance in Group 1: increased abundance in WT 1m
Revision editor(s): AaishahM
Experiment 7
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- A combination of groups WT 1m, 3m, 6m, 9m
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- WT 2m
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Wild-type mouse 2-month-old
- Group 0 sample size Number of subjects in the control (unexposed) group
- 80
- Group 1 sample size Number of subjects in the case (exposed) group
- 17
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Chao1 Abundance-based estimator of species richness
- increased
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- unchanged
- Richness Number of species
- unchanged
Signature 1
Source: Figure S3 A
Description: Differentially represented bacterial taxa of WT
Abundance in Group 1: increased abundance in WT 2m
| NCBI | Quality Control | Links |
|---|---|---|
| Muribaculaceae | ||
| uncultured Muribaculaceae bacterium |
Revision editor(s): AaishahM
Experiment 8
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- A combination of groups WT 1m, 2m, 6m, 9m
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- WT 3m
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Wild-type mouse 3-month-old
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Chao1 Abundance-based estimator of species richness
- unchanged
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- unchanged
- Richness Number of species
- unchanged
Signature 1
Source: Figure S3 A
Description: Differentially represented bacterial taxa of WT
Abundance in Group 1: increased abundance in WT 3m
Revision editor(s): AaishahM
Experiment 9
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- A combination of groups WT 1m, 2m, 3m, 9m
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- WT 6m
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Wild-type mouse 6-month-old
- Group 0 sample size Number of subjects in the control (unexposed) group
- 66
- Group 1 sample size Number of subjects in the case (exposed) group
- 31
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Chao1 Abundance-based estimator of species richness
- unchanged
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- unchanged
- Richness Number of species
- unchanged
Signature 1
Source: Figure S3 A
Description: Differentially represented bacterial taxa of WT
Abundance in Group 1: increased abundance in WT 6m
| NCBI | Quality Control | Links |
|---|---|---|
| Alloprevotella | ||
| Allobaculum | ||
| uncultured Peptococcaceae bacterium | ||
| Peptococcaceae |
Revision editor(s): AaishahM
Experiment 10
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- A combination of groups WT 1m, 2m, 3m, 6m
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- WT 9m
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Wild-type mouse 9-month-old
- Group 0 sample size Number of subjects in the control (unexposed) group
- 79
- Group 1 sample size Number of subjects in the case (exposed) group
- 18
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Chao1 Abundance-based estimator of species richness
- increased
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- unchanged
- Richness Number of species
- increased
Signature 1
Source: Figure S3 A
Description: Differentially represented bacterial taxa of WT
Abundance in Group 1: increased abundance in WT 9m
Revision editor(s): AaishahM
Experiment 11
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- A combination of groups APP/PS1 2m, 3m, 6m, 9m
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- APP/PS1 1m
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Alzheimer's Disease (AD) mouse model 1-month-old
- Group 0 sample size Number of subjects in the control (unexposed) group
- 100
- Group 1 sample size Number of subjects in the case (exposed) group
- 21
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Chao1 Abundance-based estimator of species richness
- unchanged
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- unchanged
- Richness Number of species
- unchanged
Signature 1
Source: Figure S3 B
Description: Differentially represented bacterial taxa of APP/PS1 1m
Abundance in Group 1: increased abundance in APP/PS1 1m
Revision editor(s): AaishahM
Experiment 12
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- A combination of groups APP/PS1 1m, 3m, 6m, 9m
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- APP/PS1 2m
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Alzheimer's Disease (AD) mouse model 2-month-old
- Group 0 sample size Number of subjects in the control (unexposed) group
- 97
- Group 1 sample size Number of subjects in the case (exposed) group
- 24
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Chao1 Abundance-based estimator of species richness
- increased
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- unchanged
- Richness Number of species
- unchanged
Signature 1
Source: Figure S3 B
Description: Differentially represented bacterial taxa of APP/PS1 2m
Abundance in Group 1: increased abundance in APP/PS1 2m
| NCBI | Quality Control | Links |
|---|---|---|
| Staphylococcus | ||
| Staphylococcaceae | ||
| Bacillales | ||
| Muribaculaceae | ||
| uncultured Muribaculaceae bacterium |
Revision editor(s): AaishahM
Experiment 13
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- A combination of groups APP/PS1 1m, 2m, 6m, 9m
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- APP/PS1 3m
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Alzheimer's Disease (AD) mouse model 3-month-old
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Chao1 Abundance-based estimator of species richness
- unchanged
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- unchanged
- Richness Number of species
- unchanged
Signature 1
Source: Figure S3 B
Description: Differentially represented bacterial taxa of APP/PS1 3m
Abundance in Group 1: increased abundance in APP/PS1 3m
Revision editor(s): AaishahM
Experiment 14
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- A combination of groups APP/PS1 1m, 2m, 3m, 9m
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- APP/PS1 6m
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Alzheimer's Disease (AD) mouse model 6-month-old
- Group 0 sample size Number of subjects in the control (unexposed) group
- 87
- Group 1 sample size Number of subjects in the case (exposed) group
- 34
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Chao1 Abundance-based estimator of species richness
- unchanged
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- unchanged
- Richness Number of species
- unchanged
Signature 1
Source: Figure S3 B
Description: Differentially represented bacterial taxa of APP/PS1 6m
Abundance in Group 1: increased abundance in APP/PS1 6m
| NCBI | Quality Control | Links |
|---|---|---|
| Allobaculum |
Revision editor(s): AaishahM
Experiment 15
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- A combination of groups APP/PS1 1m, 2m, 3m, 6m
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- APP/PS1 9m
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Alzheimer's Disease (AD) mouse model 9-month-old
- Group 0 sample size Number of subjects in the control (unexposed) group
- 103
- Group 1 sample size Number of subjects in the case (exposed) group
- 18
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Chao1 Abundance-based estimator of species richness
- increased
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- unchanged
- Richness Number of species
- increased
Signature 1
Source: Figure S3 B
Description: Differentially represented bacterial taxa of APP/PS1 9m
Abundance in Group 1: increased abundance in APP/PS1 9m
Revision editor(s): AaishahM
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