Altered microbiomes distinguish Alzheimer's disease from amnestic mild cognitive impairment and health in a Chinese cohort
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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
Liu P, Wu L, Peng G, Han Y, Tang R, Ge J, Zhang L, Jia L, Yue S, Zhou K, Li L, Luo B, Wang B
Journal
Brain, behavior, and immunity
Year
2019
Keywords:
Alzheimer’s disease, Amnestic mild cognitive impairment, Microbiome marker
OBJECTIVE: (Background): Alzheimer's disease (AD), clinically characterized by the progressive neurodegenerative condition and cognitive impairment, is one of the main causes of disability in elder people worldwide. Recently, several animal studies indicated that the 'gut-brain' axis might contribute to the amyloid deposition of AD. However, data about gut dysbiosis in human AD remains scarce in the literature, especially including the whole process of AD. In this prospective and cross-sectional study, we aimed at identifying differences in microbiome between patients with AD (Pre-onset stage amnestic mild cognitive impairment, aMCI; and AD) and the normal cognition healthy controls (HC). Additionally, the potential association between IM and clinical characteristics of AD was evaluated. METHODS: A total of 97 subjects (33 AD, 32 aMCI, and 32 HC) were recruited in the study. The composition of gut bacterial communities was determined by 16S ribosomal RNA Miseq sequencing. In addition, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was used to predict function shift of intestinal microbiota. The Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) or Clinical Dementia Rating (CDR) scores were used to evaluate the severity of cognitive impairment in patients. RESULTS: The fecal microbial diversity was decreased in AD patients compared with aMCI patients and HC. And the microbial composition was distinct among aMCI, AD and healthy control groups. Among bacterial taxa, the proportion of phylum Firmicutes was significantly reduced (P = 0.008), whereas Proteobacteria (P = 0.024) was highly enriched in the AD compared with HC. In addition, similar alterations were observed at the order, class and family levels of these two phyla. And Gammaproteobacteria, Enterobacteriales and Enterobacteriaceae showed a progressive enriched prevalence from HC to aMCI and AD patients. Further, a significant correlation was observed between the clinical severity scores of AD patients and the abundance of altered microbiomes. Moreover, the KEGG results showed the increased modules related to glycan biosynthesis and metabolism in AD and aMCI patients and decreased pathways related to immune system in AD patients. Importantly, the discriminating models based on predominant microbiota could effectively distinguish aMCI and AD from HC (AUC = 0.890, 0.940, respectively), and also AD from aMCI (AUC = 0.925). Notably, the models based on the abundance of family Enterobacteriaceae could distinguish AD from both aMCI (AUC = 0.688) and HC (AUC = 0.698). CONCLUSIONS: Distinct microbial communities, especially enriched Enterobacteriaceae, were associated with patients with AD when compared with predementia stage aMCI and healthy subjects. These novel findings will give new clues to understand the disease and provide new therapeutic target for intervention or a marker for this disease.
Statistical test
LEfSe
Experiment 1
Reviewed Marked as Reviewed by Claregrieve1 on 2023-5-4
Subjects
- Location of subjects
- China
- Host species Species from which microbiome was sampled (if applicable)
- 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
- 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
- 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
- Alzheimer’s disease
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients with dementia stage of alzheimer's disease.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 32
- Group 1 sample size Number of subjects in the case (exposed) group
- 33
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- Two months
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
- 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
- Matched on Factors on which subjects have been matched on in a case-control study
- age, sex
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
- Chao1 Abundance-based estimator of species richness
- unchanged
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- decreased
- Richness Number of species
- unchanged
Signature 1
Reviewed Marked as Reviewed by Claregrieve1 on 2023-5-4
Source: Figure 2
Description: Differential microbial abundance between Alzheimers patients and healthy controls
Abundance in Group 1: decreased abundance in Alzheimer’s disease
Revision editor(s): Sophy, Aiyshaaaa, Claregrieve1
Signature 2
Reviewed Marked as Reviewed by Claregrieve1 on 2023-5-4
Source: Figure 2
Description: Differential microbial abundance between Alzheimers patients and healthy controls
Abundance in Group 1: increased abundance in Alzheimer’s disease
| NCBI | Quality Control | Links |
|---|---|---|
| Gammaproteobacteria | ||
| Pseudomonadota | ||
| Enterobacterales | ||
| Enterobacteriaceae |
Revision editor(s): Sophy, Aiyshaaaa, Claregrieve1
Experiment 2
Reviewed Marked as Reviewed by Claregrieve1 on 2023-5-4
Differences from previous experiment shown
Subjects
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- aMCI patients
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients with amnestic mild cognitive impairment of alzheimer's disease.
- Group 1 sample size Number of subjects in the case (exposed) group
- 32
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
Reviewed Marked as Reviewed by Claregrieve1 on 2023-5-4
Source: Figure 2
Description: Differential microbial abundance between aMCI patients and healthy controls
Abundance in Group 1: decreased abundance in aMCI patients
| NCBI | Quality Control | Links |
|---|---|---|
| Clostridiaceae | ||
| Lachnospiraceae | ||
| Blautia |
Revision editor(s): Sophy, Claregrieve1
Signature 2
Reviewed Marked as Reviewed by Claregrieve1 on 2023-5-4
Source: Figure 2
Description: Differential microbial abundance between aMCI patients and healthy controls
Abundance in Group 1: increased abundance in aMCI patients
| NCBI | Quality Control | Links |
|---|---|---|
| Veillonellaceae | ||
| Bacteroidia | ||
| Bacteroidales | ||
| Bacteroidaceae | ||
| Bacteroides |
Revision editor(s): Sophy, Claregrieve1
Experiment 3
Reviewed Marked as Reviewed by Claregrieve1 on 2023-5-4
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Alzheimers patients in dementia stage
- Group 0 sample size Number of subjects in the control (unexposed) group
- 33
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
Reviewed Marked as Reviewed by Claregrieve1 on 2023-5-4
Source: Figure 2
Description: Differential microbial abundance between Alzheimers patients with dementia and aMCI patients
Abundance in Group 1: decreased abundance in aMCI patients
| NCBI | Quality Control | Links |
|---|---|---|
| Enterobacterales | ||
| Enterobacteriaceae | ||
| Gammaproteobacteria | ||
| Pseudomonadota |
Revision editor(s): Sophy, Aiyshaaaa, Claregrieve1
Signature 2
Reviewed Marked as Reviewed by Claregrieve1 on 2023-5-4
Source: Figure 2
Description: Differential microbial abundance between Alzheimers patients with dementia and aMCI patients
Abundance in Group 1: increased abundance in aMCI patients
| NCBI | Quality Control | Links |
|---|---|---|
| Clostridiaceae | ||
| Ruminococcus | ||
| Clostridia | ||
| Bacteroidia | ||
| Clostridiales bacterium | ||
| Bacteroidales | ||
| Oscillospiraceae | ||
| Bacteroidaceae | ||
| Bacteroides |
Revision editor(s): Sophy, Claregrieve1
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