Injection of amyloid-β to lateral ventricle induces gut microbiota dysbiosis in association with inhibition of cholinergic anti-inflammatory pathways in 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
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Qian XH, Liu XL, Chen G, Chen SD, Tang HD
Journal
Journal of neuroinflammation
Year
2022
Keywords:
Alzheimer’s disease, Aβ, Cholinergic anti-inflammatory pathway, Gut microbiota
BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative disease and its pathogenesis is still unclear. There is dysbiosis of gut microbiota in AD patients. More importantly, dysbiosis of the gut microbiota has been observed not only in AD patients, but also in patients with mild cognitive impairment (MCI). However, the mechanism of gut microbiota dysbiosis in AD is poorly understood. Cholinergic anti-inflammatory pathway is an important pathway for the central nervous system (CNS) regulation of peripheral immune homeostasis, especially in the gut. Therefore, we speculated that dysfunction of cholinergic anti-inflammatory pathway is a potential pathway for dysbiosis of the gut microbiota in AD. METHODS: In this study, we constructed AD model mice by injecting Aβ1-42 into the lateral ventricle, and detected the cognitive level of mice by the Morris water maze test. In addition, 16S rDNA high-throughput analysis was used to detect the gut microbiota abundance of each group at baseline, 2 weeks and 4 weeks after surgery. Furthermore, immunofluorescence and western blot were used to detect alteration of intestinal structure of mice, cholinergic anti-inflammatory pathway, and APP process of brain and colon in each group. RESULTS: Aβ1-42 i.c.v induced cognitive impairment and neuron damage in the brain of mice. At the same time, Aβ1-42 i.c.v induced alteration of gut microbiota at 4 weeks after surgery, while there was no difference at the baseline and 2 weeks after surgery. In addition, changes in colon structure and increased levels of pro-inflammatory factors were detected in Aβ1-42 treatment group, accompanied by inhibition of cholinergic anti-inflammatory pathways. Amyloidogenic pathways in both the brain and colon were accelerated in Aβ1-42 treatment group. CONCLUSIONS: The present findings suggested that Aβ in the CNS can induce gut microbiota dysbiosis, alter intestinal structure and accelerate the amyloidogenic pathways, which were related to inhibiting cholinergic anti-inflammatory pathways.
Experiment 3
Reviewed Marked as Reviewed by Svetlana up on 2024-6-28
Differences from previous experiment shown
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
- Sham-operated group
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Alzheimer’s disease (4 weeks after surgery)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Alzheimer's disease (AD) model mice injected in the lateral ventricle with Aβ1–42 intracerebroventricular injection 4 weeks after surgery
- Group 0 sample size Number of subjects in the control (unexposed) group
- 10
- Group 1 sample size Number of subjects in the case (exposed) group
- 10
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
- Statistical test
- ANOVA
- 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
Alpha Diversity
- 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
- increased
- Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
- increased
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2024-6-28
Source: Figure 3 (I - N)
Description: Bacterial genera significantly different at the genus level in the Aβ1–42 treatment group compared to the phosphate-buffered saline (PBS) sham-operated group
Abundance in Group 1: increased abundance in Alzheimer’s disease (4 weeks after surgery)
| NCBI | Quality Control | Links |
|---|---|---|
| Adlercreutzia | ||
| Akkermansia | ||
| Rikenella |
Revision editor(s): Flo, Scholastica
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2024-6-28
Source: Figure 3 (I - N)
Description: Bacterial genera significantly different at the genus level in the Aβ1–42 treatment group compared to the phosphate-buffered saline (PBS) sham-operated group
Abundance in Group 1: decreased abundance in Alzheimer’s disease (4 weeks after surgery)
| NCBI | Quality Control | Links |
|---|---|---|
| Alloprevotella | ||
| Ruminiclostridium | ||
| Streptococcus |
Revision editor(s): Flo, Scholastica
Experiment 6
Reviewed Marked as Reviewed by Svetlana up on 2024-6-28
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Control group
Lab analysis
Statistical Analysis
Alpha Diversity
- 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
- increased
- Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
- increased
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2024-6-28
Source: Figure 3 (I - N)
Description: Bacterial genera significantly different at the genus level in the Aβ1–42 treatment group compared to the control group
Abundance in Group 1: increased abundance in Alzheimer’s disease (4 weeks after surgery)
| NCBI | Quality Control | Links |
|---|---|---|
| Adlercreutzia | ||
| Akkermansia | ||
| Rikenella |
Revision editor(s): Flo, Scholastica
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2024-6-28
Source: Figure 3 (I - N)
Description: Bacterial genera significantly different at the genus level in the Aβ1–42 treatment group compared to the control group
Abundance in Group 1: decreased abundance in Alzheimer’s disease (4 weeks after surgery)
| NCBI | Quality Control | Links |
|---|---|---|
| Alloprevotella | ||
| Ruminiclostridium | ||
| Streptococcus |
Revision editor(s): Flo, Scholastica
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