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

From BugSigDB
Reviewed Marked as Reviewed by Svetlana up on 2024-7-15
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
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


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

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

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 ControlLinks
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

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

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 ControlLinks
Thomasclavelia
Tyzzerella

Revision editor(s): Scholastica