Modulation of the Gut Microbiota in Memory Impairment and Alzheimer's Disease via the Inhibition of the Parasympathetic Nervous System
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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
Park S, Wu X
Journal
International journal of molecular sciences
Year
2022
Keywords:
Alzheimer’s disease, gut dysbiosis, mild memory impairment, parasympathetic nervous system, scopolamine
The gut microbiota has been demonstrated to play a critical role in maintaining cognitive function via the gut-brain axis, which may be related to the parasympathetic nervous system (PNS). However, the exact mechanism remains to be determined. We investigated that patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) could exhibit an altered gut microbiota through the suppression of the PNS, compared to the healthy individuals, using the combined gut microbiota data from previous human studies. The hypothesis was validated in rats to suppress the PNS by scopolamine injections. The human fecal bacterial FASTA/Q files were selected and combined from four different AD studies (n = 410). All rats had a high-fat diet and treatments for six weeks. The MD rats had memory impairment by scopolamine injection (2 mg/kg body weight; MD, Control) or no memory impairment by saline injection. The scopolamine-injected rats had a donepezil intake as the positive group. In the optimal model generated from the XGboost analysis, Blautia luti, Pseudomonas mucidoiens, Escherichia marmotae, and Gemmiger formicillis showed a positive correlation with MCI while Escherichia fergusonii, Mycobacterium neglectum, and Lawsonibacter asaccharolyticus were positively correlated with AD in the participants with enterotype Bacteroides (ET-B, n = 369). The predominant bacteria in the AD group were negatively associated in the networking analysis with the bacteria in the healthy group of ET-B participants. From the animal study, the relative abundance of Bacteroides and Bilophilia was lower, and that of Escherichia, Blautia, and Clostridium was higher in the scopolamine-induced memory deficit (MD) group than in the normal group. These results suggest that MCI was associated with the PNS suppression and could progress to AD by exacerbating the gut dysbiosis. MCI increased Clostridium and Blautia, and its progression to AD elevated Escherichia and Pseudomonas. Therefore, the modulation of the PNS might be linked to an altered gut microbiota and brain function, potentially through the gut-brain axis.
Experiment 1
Reviewed Marked as Reviewed by Svetlana up on 2024-7-1
Subjects
- 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
- Gut microbiome measurement Gut microbiome measurement,gut microbiome measurement
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Healthy group
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Mild cognitive impairment (MCI) and Alzheimer’s disease (AD)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients with mild cognitive impairment (MCI) and Alzheimer’s disease (AD)
- Group 0 sample size Number of subjects in the control (unexposed) group
- 125
- Group 1 sample size Number of subjects in the case (exposed) group
- 244
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- None
Lab analysis
- Sequencing type
- 16S
- 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
- 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
- 3
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
- Chao1 Abundance-based estimator of species richness
- decreased
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2024-7-1
Source: Figure 3A
Description: Linear discriminant analysis (LDA) scores of the bacteria at the genus level significantly different in healthy group versus mild cognitive impairment (MCI) and Alzheimer’s disease (AD)
Abundance in Group 1: decreased abundance in Mild cognitive impairment (MCI) and Alzheimer’s disease (AD)
| NCBI | Quality Control | Links |
|---|---|---|
| Alistipes | ||
| Bacteroides | ||
| Parabacteroides | ||
| Phocaeicola | ||
| Ruminococcus |
Revision editor(s): Samreen-19, Scholastica
Experiment 2
Reviewed Marked as Reviewed by Svetlana up on 2024-7-1
Differences from previous experiment shown
Subjects
- 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
- Healthy group and mild cognitive impairment (MCI)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Alzheimer’s disease (AD)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients with Alzheimer’s disease (AD)
- Group 0 sample size Number of subjects in the control (unexposed) group
- 266
- Group 1 sample size Number of subjects in the case (exposed) group
- 103
Lab analysis
Statistical Analysis
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2024-7-1
Source: Figure 3A
Description: Linear discriminant analysis (LDA) scores of the bacteria at the genus level significantly different in healthy group and mild cognitive impairment (MCI) versus Alzheimer’s disease (AD)
Abundance in Group 1: increased abundance in Alzheimer’s disease (AD)
| NCBI | Quality Control | Links |
|---|---|---|
| Escherichia |
Revision editor(s): Samreen-19, Scholastica
Experiment 3
Reviewed Marked as Reviewed by Svetlana up on 2024-7-1
Differences from previous experiment shown
Subjects
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Cognitive impairment Abnormality of cognition,Cognitive abnormality,Cognitive defects,Cognitive deficits,Cognitive impairment,Intellectual impairment,cognitive impairment
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Healthy group and Alzheimer's Disease (AD)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Mild Cognitive Impairment (MCI)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients with mild cognitive impairment (MCI)
- Group 0 sample size Number of subjects in the control (unexposed) group
- 228
- Group 1 sample size Number of subjects in the case (exposed) group
- 141
Lab analysis
Statistical Analysis
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2024-7-1
Source: Figure 3A
Description: Linear discriminant analysis (LDA) scores of the bacteria at the genus level significantly different in healthy group and mild cognitive impairment (MCI) versus Alzheimer’s disease (AD)
Abundance in Group 1: increased abundance in Mild Cognitive Impairment (MCI)
| NCBI | Quality Control | Links |
|---|---|---|
| Blautia | ||
| Collinsella | ||
| Faecalibacterium | ||
| Lachnospira | ||
| Streptococcus | ||
| Thomasclavelia |
Revision editor(s): Samreen-19, Scholastica
Experiment 4
Reviewed Marked as Reviewed by Svetlana up on 2024-7-1
Differences from previous experiment shown
Subjects
- Location of subjects
- South Korea
- Host species Species from which microbiome was sampled. Contact us to have more species added.
- Rattus norvegicus
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Memory impairment Memory Impairment Adverse Event,Memory impairment,memory impairment
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Normal health group
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Positive and memory deficit (MD) group
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Rats divided into the positive group (n = 10) given intraperitoneal scopolamine plus donepezil injection and those belonging to the memory deficit (MD) group (n = 10) given intraperitoneal scopolamine injection
- 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
- 20
Lab analysis
- 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, Roche454
Statistical Analysis
- LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
- 2
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2024-7-1
Source: Figure 6F
Description: LDA scores of the bacteria at the species level significantly different in normal health group versus positive and memory deficit (MD) group
Abundance in Group 1: decreased abundance in Positive and memory deficit (MD) group
Revision editor(s): Samreen-19, Scholastica
Experiment 5
Reviewed Marked as Reviewed by Svetlana up on 2024-7-1
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Normal health group and memory deficit (MD) group
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Positive group
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Rats in the positive group (n = 10) given intraperitoneal scopolamine plus donepezil injection
- Group 0 sample size Number of subjects in the control (unexposed) group
- 20
- Group 1 sample size Number of subjects in the case (exposed) group
- 10
Lab analysis
Statistical Analysis
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2024-7-1
Source: Figure 6F
Description: LDA scores of the bacteria at the species level significantly different in positive group versus normal health and memory deficit (MD) group
Abundance in Group 1: increased abundance in Positive group
| NCBI | Quality Control | Links |
|---|---|---|
| Bacteroides finegoldii | ||
| Bifidobacterium longum | ||
| Bifidobacterium pseudolongum | ||
| Collinsella aerofaciens | ||
| Limosilactobacillus reuteri | ||
| Subdoligranulum variabile |
Revision editor(s): Samreen-19, Scholastica
Experiment 6
Reviewed Marked as Reviewed by Svetlana up on 2024-7-1
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Normal health group and positive group
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Memory deficit (MD) group
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Rats in the memory deficit (MD) group (n = 10) given intraperitoneal scopolamine injection
Lab analysis
Statistical Analysis
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2024-7-1
Source: Figure 6F
Description: LDA scores of the bacteria at the species level significantly different in memory deficit (MD) group versus normal health and positive group
Abundance in Group 1: increased abundance in Memory deficit (MD) group
Revision editor(s): Scholastica
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