Gut microbiome characteristics in subjective cognitive decline, mild cognitive impairment and Alzheimer's disease: a systematic review and meta-analysis

Study information

Reviewed Marked as Reviewed by KateRasheed on 2025-6-12

study design

meta-analysis

Citation

PMID PubMed identifier for scientific articles.

37399128

DOI Digital object identifier for electronic documents.

https://doi.org/10.1111/ene.15961

URI Uniform resource identifier for web resources.

Authors

Chen G, Zhou X, Zhu Y, Shi W, Kong L

Journal

European journal of neurology

Year

2023

Keywords:

Alzheimer's disease, alpha diversity, gut microbes, relative abundance

BACKGROUND AND PURPOSE: The gut microbiome has been reported to be closely related to Alzheimer's disease (AD) progression. Here, a comprehensive meta-analysis of gut microbial characteristics in AD, mild cognitive impairment (MCI) and subjective cognitive decline (SCD) was performed to compare gut microbial alterations at each stage. METHODS: A total of 10 databases (CNKI, WanFang, VIP, SinoMed, WOS, PubMed, Embase, Cochrane Library, PsycINFO and Void) were searched and 34 case-control studies were included. α and β diversity and the relative abundance of gut microbiota were analysed as outcome indices. Data analysis was performed using Review Manager (5.4.1) and R. RESULTS: Chao1 and Shannon index levels in AD were significantly lower compared with healthy controls (HCs), and the Chao1 index was significantly lower in MCI compared with HCs. There was a significant difference in β diversity of gut microbiomes in patients (SCD, MCI, AD) compared with HCs. The relative abundance of Firmicutes at the phylum level was significantly lower in patients with AD and MCI than HCs. However, the relative abundance of Bacteroidetes at the phylum level was significantly higher in patients with MCI than HCs. There was an increasing trend for Enterobacteriaceae and a decreasing trend for Ruminococcaceae, Lachnospiraceae and Lactobacillus during AD; Lactobacillus showed a decreasing trend early in SCD. CONCLUSION: Our results indicated that there were gut microbiological abnormalities in AD, even as early as the SCD stage. The dynamic, consistent changes in gut microbes with the disease process showed that they might serve as potential biomarkers for early identification and diagnosis of AD.

Experiment 1

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Reviewed Marked as Reviewed by KateRasheed on 2025-6-12

Curated date: 2025/05/01

Curator: Aiyshaaaa

Revision editor(s): Aiyshaaaa, Fiddyhamma

Subjects

Location of subjects: China; United States of America

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: Healthy Controls (HC)

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: Individuals who have been diagnosed with Alzheimer's disease (AD)

Group 0 sample size Number of subjects in the control (unexposed) group: 128

Group 1 sample size Number of subjects in the case (exposed) group: 129

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: Random Forest Analysis

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

Shannon Estimator of species richness and species evenness: more weight on species richness: decreased

Chao1 Abundance-based estimator of species richness: decreased

Simpson Estimator of species richness and species evenness: more weight on species evenness: unchanged

Richness Number of species: unchanged

Signature 1

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Curated date: 2025/05/07

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Revision editor(s): Aiyshaaaa

Source: Fig-1b

Description: Forest plots of the estimated relative abundance of phylum Firmicutes, in patients with AD compared to HCs.

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

NCBI	Quality Control	Links
Bacillota

Revision editor(s): Aiyshaaaa

Experiment 2

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Reviewed Marked as Reviewed by KateRasheed on 2025-6-12

Curated date: 2025/05/07

Curator: Aiyshaaaa

Revision editor(s): Aiyshaaaa, Fiddyhamma

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 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: Individuals who have been diagnosed with Mild cognitive impairment(MCI)

Group 0 sample size Number of subjects in the control (unexposed) group: 131

Group 1 sample size Number of subjects in the case (exposed) group: 137

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: decreased

Simpson Estimator of species richness and species evenness: more weight on species evenness: unchanged

Signature 1

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Reviewed Marked as Reviewed by KateRasheed on 2025-6-12

Curated date: 2025/05/07

Curator: Aiyshaaaa

Revision editor(s): Aiyshaaaa, Fiddyhamma

Source: Fig 1A

Description: Forest plots of the estimated relative abundance of phylum Bacteroidetes, phylum Firmicutes in patients with MCI compared to HCs

Abundance in Group 1: increased abundance in Mild cognitive impairment(MCI)

NCBI	Quality Control	Links
Bacteroidota

Revision editor(s): Aiyshaaaa, Fiddyhamma

Experiment 3

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Reviewed Marked as Reviewed by KateRasheed on 2025-6-12

Curated date: 2025/06/11

Curator: Fiddyhamma

Revision editor(s): Fiddyhamma

Differences from previous experiment shown

Subjects

Group 0 sample size Number of subjects in the control (unexposed) group: 168

Group 1 sample size Number of subjects in the case (exposed) group: 149

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: decreased

Simpson Estimator of species richness and species evenness: more weight on species evenness: unchanged

Signature 1

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Reviewed Marked as Reviewed by KateRasheed on 2025-6-12

Curated date: 2025/06/11

Curator: Fiddyhamma

Revision editor(s): Fiddyhamma

Source: Figure 1B

Description: Forest plots of the estimated relative abundance of phylum Bacteroidetes, phylum Firmicutes in patients with MCI compared to HCs

Abundance in Group 1: decreased abundance in Mild cognitive impairment(MCI)

NCBI	Quality Control	Links
Bacillota

Revision editor(s): Fiddyhamma