Disturbed microbial ecology in Alzheimer's disease: evidence from the gut microbiota and fecal metabolome

Study information

Reviewed Marked as Reviewed by Svetlana up on 2024-7-15

study design

case-control

Citation

PMID PubMed identifier for scientific articles.

34384375

DOI Digital object identifier for electronic documents.

10.1186/s12866-021-02286-z

URI

Authors

Xi J, Ding D, Zhu H, Wang R, Su F, Wu W, Xiao Z, Liang X, Zhao Q, Hong Z, Fu H, Xiao Q

Journal

BMC microbiology

Year

2021

Keywords:

Alzheimer’s disease, Fecal markers, Fecal metabolome, Gut microbiota, Inflammatory cytokines

BACKGROUND: Gut microbiota (GMB) alteration has been reported to influence the Alzheimer's disease (AD) pathogenesis through immune, endocrine, and metabolic pathways. This study aims to investigate metabolic output of the dysbiosis of GMB in AD pathogenesis. In this study, the fecal microbiota and metabolome from 21 AD participants and 44 cognitively normal control participants were measured. Untargeted GMB taxa was analyzed through 16S ribosomal RNA gene profiling based on next-generation sequencing and fecal metabolites were quantified by using ultrahigh performance liquid chromatography-mass spectrometry (UPLC-MS). RESULTS: Our analysis revealed that AD was characterized by 15 altered gut bacterial genera, of which 46.7% (7/15 general) was significantly associated with a series of metabolite markers. The predicted metabolic profile of altered gut microbial composition included steroid hormone biosynthesis, N-Acyl amino acid metabolism and piperidine metabolism. Moreover, a combination of 2 gut bacterial genera (Faecalibacterium and Pseudomonas) and 4 metabolites (N-Docosahexaenoyl GABA, 19-Oxoandrost-4-ene-3,17-dione, Trigofoenoside F and 22-Angeloylbarringtogenol C) was able to discriminate AD from NC with AUC of 0.955 in these 65 subjects. CONCLUSIONS: These findings demonstrate that gut microbial alterations and related metabolic output changes may be associated with pathogenesis of AD, and suggest that fecal markers might be used as a non-invasive examination to assist screening and diagnosis of AD.

Experiment 1

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Reviewed Marked as Reviewed by Svetlana up on 2024-7-15

Curated date: 2024/03/21

Curator: Scholastica

Revision editor(s): Scholastica

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: Cognitively normal control (NC)

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: Participants with Alzheimer’s Disease (AD); the most prevalent neurodegenerative disorder.

Group 0 sample size Number of subjects in the control (unexposed) group: 44

Group 1 sample size Number of subjects in the case (exposed) group: 21

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): 1 month

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: 2.5

Alpha Diversity

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

Chao1 Abundance-based estimator of species richness: unchanged

Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa: unchanged

Richness Number of species: unchanged

Signature 1

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Curated date: 2024/03/21

Curator: Scholastica

Revision editor(s): Scholastica

Source: Fig. 1B

Description: Taxonomic differences of gut microbiota bacterial in Alzheimer’s disease (AD) versus cognitively normal control (NC) participants analyzed by Linear discriminant analysis (LDA) effect size (LEfSe)

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

NCBI	Quality Control	Links
Agathobacter
Alloprevotella
Atopobium
Cloacibacillus
Coprococcus
Eubacterium ventriosum
Faecalibacterium
Lachnospiraceae bacterium NC2004
Parvimonas
Pseudomonas
Solobacterium
unclassified Lachnospiraceae
Ruminococcaceae bacterium UCG-007Ruminococcaceae bacterium UCG-007

Revision editor(s): Scholastica

Signature 2

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Curated date: 2024/03/21

Curator: Scholastica

Revision editor(s): Scholastica

Source: Fig. 1B

Description: Taxonomic differences of gut microbiota bacterial in Alzheimer’s disease (AD) versus cognitively normal control (NC) participants analyzed by Linear discriminant analysis (LDA) effect size (LEfSe)

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

NCBI	Quality Control	Links
Thomasclavelia
Tyzzerella

Revision editor(s): Scholastica