Mild cognitive impairment has similar alterations as Alzheimer's disease in gut microbiota

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Citation
PMID PubMed identifier for scientific articles.
31434623
DOI Digital object identifier for electronic documents.
10.1016/j.jalz.2019.07.002
URI
Authors
Li B, He Y, Ma J, Huang P, Du J, Cao L, Wang Y, Xiao Q, Tang H, Chen S
Journal
Alzheimer's & dementia : the journal of the Alzheimer's Association
Year
2019
Keywords:
16S rRNA gene, Alzheimer's disease, Amyloid, Fecal microbiota, Mild cognitive impairment
OBJECTIVE: Gut microbiota changes before the onset of Alzheimer's disease (AD) and the alterations could be detected in the stage of mild cognitive impairment (MCI). The findings might offer diagnostic biomarkers before the onset of dementia. BACKGROUND: AD is the most common cause of dementia, and MCI is the predementia state. Recent studies suggest the alterations in the gut microbial communities associated with AD, whereas the microbiota in MCI before the onset of dementia has not been discovered and characterized in humans. NEW/UPDATED HYPOTHESIS: We hypothesize that the dysbiosis happens in the MCI stage. Patients with AD and MCI have decreased microbial diversity, and changes in gut microbiota could be detected for early detection of AD. In our preliminary study, we identified differences between AD and normal controls in 11 genera from the feces and 11 genera from the blood. No difference in genera between AD and MCI was detected. Using the diagnostic model from fecal samples with all different genera input, 93% (28 in 30) of patients with MCI could be identified correctly. MAJOR CHALLENGES FOR THE HYPOTHESIS: The diagnosis of MCI and AD in the study was based on symptoms and neuroimaging, and AD biomarkers should be included for precise diagnosis in further validating studies. Besides, as the microbiota changes longitudinally, their relationship with the progress of dementia needs to be studied in the prospective studies. LINKAGE TO OTHER MAJOR THEORIES: Escherichia was observed increased at genus level in both fecal and blood samples from AD and MCI. For AD biomarker, postmortem brain tissue from patients with AD showed lipopolysaccharides and gram-negative Escherichia coli fragments colocalize with amyloid plaque. In this way, the amyloid pathogenesis for AD would be triggered during MCI by gut microbiota shifting. Besides, systemic inflammatory reactions caused by compounds secreted by bacteria may impair the blood-brain barrier and promote neuroinflammation and/or neurodegeneration. Furthermore, abnormal metabolites caused by microbial gene functions have an impact on neurodegeneration.

Experiment 1


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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
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
Normal Controls
Group 1 name Corresponds to the case (exposed) group for case-control studies
Alzheimer's Disease (AD) patients
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with Alzheimer's Disease
Group 0 sample size Number of subjects in the control (unexposed) group
30
Group 1 sample size Number of subjects in the case (exposed) group
30

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
2.0


Signature 1

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Source: Figure 2A + Figure S1A

Description: Taxonomic differences of fecal microbiota in patients with AD and normal controls

Abundance in Group 1: increased abundance in Alzheimer's Disease (AD) patients

NCBI Quality ControlLinks
Acinetobacter   
Actinomycetota   
Akkermansia   
Bacilli   
Bifidobacteriaceae   
Bifidobacteriales   
Bifidobacterium   
Blautia   
Clostridia   
Coriobacteriaceae   
Coriobacteriales   
Coriobacteriia   
Dorea   
Erysipelotrichaceae   
Erysipelotrichales   
Fusobacteriaceae   
Fusobacteriales   
Fusobacteriia   
Lachnospiraceae   
Lactobacillaceae   
Lactobacillales   
Lactobacillus   
Streptococcaceae   
Streptococcus   
Verrucomicrobiaceae   
Verrucomicrobiales   
Verrucomicrobiia   

Revision editor(s): AaishahM

Signature 2

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Source: Figure 2A + Figure S1A

Description: Taxonomic differences of fecal microbiota in patients with AD and normal controls

Abundance in Group 1: decreased abundance in Alzheimer's Disease (AD) patients

NCBI Quality ControlLinks
Aeromonadales   
Alcaligenaceae   
Alistipes   
Alloprevotella   
Bacteroidaceae   
Bacteroidales   
Bacteroides   
Bacteroidia   
Barnesiella   
Betaproteobacteria   
Burkholderiales   
Butyricimonas   
Haemophilus   
Parabacteroides   
Paraprevotella   
Pasteurellaceae   
Pasteurellales   
Porphyromonadaceae   
Prevotella   
Prevotellaceae   
Rhodospirillaceae   
Rhodospirillales   
Succinivibrio   
Succinivibrionaceae   
Sutterella   

Revision editor(s): AaishahM

Experiment 2


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Differences from previous experiment shown

Subjects

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Blood Portion of blood,Vertebrate blood,Whole blood,Blood,blood


Lab analysis

Statistical Analysis

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

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Source: Figure 2B + Figure S1B

Description: Taxonomic differences of blood microbiota in patients with AD and normal controls

Abundance in Group 1: increased abundance in Alzheimer's Disease (AD) patients

NCBI Quality ControlLinks
Acidovorax   
Escherichia   
Glutamicibacter   
Pelagibacterium   
Propionibacterium   
Pseudomonas   
Staphylococcus   
Stenotrophomonas   
Sulfuritalea   
Vibrionimonas   
Propionibacteriaceae   
Propionibacteriales   
Chitinophagaceae   
Sphingobacteriales   
Sphingobacteriia   
Staphylococcaceae   
Bacillales   
Bacilli   
Hyphomicrobiaceae   
Sphingomonadaceae   
Sphingomonadales   
Comamonadaceae   
Burkholderiales   
Betaproteobacteria   
Pseudomonadaceae   
Pseudomonadales   
Lysobacteraceae   
Gammaproteobacteria   
Pseudomonadota   

Revision editor(s): AaishahM

Signature 2

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Source: Figure 2B + Figure S1B

Description: Taxonomic differences of blood microbiota in patients with AD and normal controls

Abundance in Group 1: decreased abundance in Alzheimer's Disease (AD) patients

NCBI Quality ControlLinks
Achromobacter   
Acinetobacter baumannii   
Brevundimonas   
Enterobacter   
Halomonas   
Leucobacter   
Methylobacterium   
Nesterenkonia   
Ochrobactrum   
Serratia   
Microbacteriaceae   
Micrococcales   
Actinomycetota   
Caulobacteraceae   
Hyphomonadaceae   
Caulobacterales   
Brucellaceae   
Methylobacteriaceae   
Phyllobacteriaceae   
Hyphomicrobiales   
Paracoccaceae   
Rhodobacterales   
Rhodospirillales   
Alphaproteobacteria   
Alcaligenaceae   
Halomonadaceae   
Oceanospirillaceae   
Moraxellaceae   

Revision editor(s): AaishahM

Experiment 3


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Differences from previous experiment shown

Subjects

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


Lab analysis

Statistical Analysis

Statistical test
Linear Regression
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
Yes
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
Not specified
Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, body mass index, constipation, Confounders controlled for: "gender" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.gender


Signature 1

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Source: Table 2

Description: Generalized linear model for significant genera in AD patients and normal controls

Abundance in Group 1: increased abundance in Alzheimer's Disease (AD) patients

NCBI Quality ControlLinks
Blautia   
Bifidobacterium   
Streptococcus   
Lactobacillus   
Dorea   

Revision editor(s): AaishahM

Signature 2

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Source: Table 2

Description: Generalized linear model for significant genera in AD patients and normal controls

Abundance in Group 1: decreased abundance in Alzheimer's Disease (AD) patients

NCBI Quality ControlLinks
Alistipes   
Bacteroides   
Parabacteroides   
Sutterella   
Paraprevotella   

Revision editor(s): AaishahM

Experiment 4


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Differences from previous experiment shown

Subjects

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Blood Portion of blood,Vertebrate blood,Whole blood,Blood,blood
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Normal Controsl

Lab analysis

Statistical Analysis

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, Confounders controlled for: "gender" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.gender, body mass index, constipation


Signature 1

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Curated date: 2024/12/11

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Source: Table 2

Description: Generalized linear model for significant genera in AD patients and normal controls

Abundance in Group 1: increased abundance in Alzheimer's Disease (AD) patients

NCBI Quality ControlLinks
Acidovorax   
Escherichia   
Glutamicibacter   
Pseudomonas   
Propionibacterium   

Revision editor(s): AaishahM

Signature 2

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Source: Table 2

Description: Generalized linear model for significant genera in AD patients and normal controls

Abundance in Group 1: decreased abundance in Alzheimer's Disease (AD) patients

NCBI Quality ControlLinks
Acinetobacter   
Halomonas   
Leucobacter   
Ochrobactrum   

Revision editor(s): AaishahM

Experiment 5


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Differences from previous experiment shown

Subjects

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
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Normal Controls

Lab analysis

Statistical Analysis

Statistical test
Kruskall-Wallis
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
No
Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
Not specified


Signature 1

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Source: Figure 3

Description: Relative abundance comparing AD patients and controls

Abundance in Group 1: increased abundance in Alzheimer's Disease (AD) patients

NCBI Quality ControlLinks
Escherichia   
Lactobacillus   

Revision editor(s): AaishahM

Signature 2

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Source: Figure 3

Description: Relative abundance comparing AD patients and controls

Abundance in Group 1: decreased abundance in Alzheimer's Disease (AD) patients

NCBI Quality ControlLinks
Bacteroides   

Revision editor(s): AaishahM

Experiment 6


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Differences from previous experiment shown

Subjects

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

Lab analysis

Statistical Analysis

Signature 1

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Source: Figure 3

Description: Relative abundance comparing MCI patients and controls

Abundance in Group 1: increased abundance in Mild Cognitive Impairment (MCI)

NCBI Quality ControlLinks
Escherichia   
Lactobacillus   

Revision editor(s): AaishahM

Signature 2

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Source: Figure 3

Description: Relative abundance comparing MCI patients and controls

Abundance in Group 1: decreased abundance in Mild Cognitive Impairment (MCI)

NCBI Quality ControlLinks
Bacteroides   

Revision editor(s): AaishahM

Experiment 7


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Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
Alzheimer's Disease (AD) patients
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with Alzheimer's Disease

Lab analysis

Statistical Analysis

Statistical test
Linear Regression


Signature 1

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Source: Table S1

Description: Differences of the fecal microbiota at all levels between AD and normal controls

Abundance in Group 1: increased abundance in Alzheimer's Disease (AD) patients

NCBI Quality ControlLinks
Actinomycetota   
Candidatus Saccharibacteria   
Verrucomicrobiota   
Bacilli   
Clostridia   
Coriobacteriia   
Erysipelotrichia   
Verrucomicrobiia   
Bifidobacteriales   
Eubacteriales   
Coriobacteriales   
Erysipelotrichales   
Lactobacillales   
Verrucomicrobiales   
Bifidobacteriaceae   
Coriobacteriaceae   
Erysipelotrichaceae   
Lachnospiraceae   
Lactobacillaceae   
Streptococcaceae   
Verrucomicrobiaceae   
Akkermansia   
Bifidobacterium   
Blautia   
Dorea   
Eggerthella   
Lactobacillus   
Streptococcus   

Revision editor(s): AaishahM

Signature 2

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Source: Table S1

Description: Differences of the fecal microbiota at all levels between AD and normal controls

Abundance in Group 1: decreased abundance in Alzheimer's Disease (AD) patients

NCBI Quality ControlLinks
Bacteroidia   
Betaproteobacteria   
Bacteroidales   
Burkholderiales   
Pasteurellales   
Alcaligenaceae   
Bacteroidaceae   
Pasteurellaceae   
Porphyromonadaceae   
Prevotellaceae   
Rikenellaceae   
Alistipes   
Bacteroides   
Butyricimonas   
Haemophilus   
Lachnospira   
Parabacteroides   
Paraprevotella   
Prevotella   

Revision editor(s): AaishahM

Experiment 8


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Differences from previous experiment shown

Subjects

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Blood Portion of blood,Vertebrate blood,Whole blood,Blood,blood


Lab analysis

Statistical Analysis

Signature 1

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Source: Table S2

Description: Differences of the blood microbiota at all levels between AD and normal controls

Abundance in Group 1: increased abundance in Alzheimer's Disease (AD) patients

NCBI Quality ControlLinks
Bacilli   
Betaproteobacteria   
Gammaproteobacteria   
Sphingobacteriia   
Bacillales   
Burkholderiales   
Propionibacteriales   
Pseudomonadales   
Sphingobacteriales   
Comamonadaceae   
Hyphomicrobiaceae   
Propionibacteriaceae   
Pseudomonadaceae   
Sphingomonadaceae   
Staphylococcaceae   
Lysobacteraceae   
Acidovorax   
Blautia   
Escherichia   
Glutamicibacter   
Legionella   
Novosphingobium   
Pelagibacterium   
Propionibacterium   
Pseudomonas   
Skermanella   
Staphylococcus   
Stenotrophomonas   
Sulfuritalea   
Vibrionimonas   

Revision editor(s): AaishahM

Signature 2

EditHistoryDelete
Mark reviewed
Your review change was submitted
Needs review

Curated date: 2024/12/13

Curator: AaishahM

Revision editor(s): AaishahM

Source: Table S2

Description: Differences of the blood microbiota at all levels between AD and normal controls

Abundance in Group 1: decreased abundance in Alzheimer's Disease (AD) patients

NCBI Quality ControlLinks
Actinomycetota   
Alphaproteobacteria   
Caulobacterales   
Micrococcales   
Oceanospirillales   
Hyphomicrobiales   
Rhodobacterales   
Rhodospirillales   
Alcaligenaceae   
Brucellaceae   
Caulobacteraceae   
Halomonadaceae   
Moraxellaceae   
Oxalobacteraceae   
Phyllobacteriaceae   
Paracoccaceae   
Rhodospirillaceae   
Brevundimonas   
Enterobacter   
Halomonas   
Leucobacter   
Methyloversatilis   
Nesterenkonia   
Ochrobactrum   
Psychrobacter   
Serratia   
Undibacterium   

Revision editor(s): AaishahM

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