Profiles of subgingival microbiomes and gingival crevicular metabolic signatures in patients with amnestic mild cognitive impairment and Alzheimer's disease

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Reviewed Marked as Reviewed by Svetlana up on 2024-6-14
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Qiu C, Zhou W, Shen H, Wang J, Tang R, Wang T, Xie X, Hong B, Ren R, Wang G, Song Z
Journal
Alzheimer's research & therapy
Year
2024
Keywords:
Alzheimer’s disease, Metabolome, Microbiome, Mild cognitive impairment, Multiomics, Periodontitis
BACKGROUND: The relationship between periodontitis and Alzheimer's disease (AD) has attracted more attention recently, whereas profiles of subgingival microbiomes and gingival crevicular fluid (GCF) metabolic signatures in AD patients have rarely been characterized; thus, little evidence exists to support the oral-brain axis hypothesis. Therefore, our study aimed to characterize both the microbial community of subgingival plaque and the metabolomic profiles of GCF in patients with AD and amnestic mild cognitive impairment (aMCI) for the first time. METHODS: This was a cross-sectional study. Clinical examinations were performed on all participants. The microbial community of subgingival plaque and the metabolomic profiles of GCF were characterized using the 16S ribosomal RNA (rRNA) gene high-throughput sequencing and liquid chromatography linked to tandem mass spectrometry (LC-MS/MS) analysis, respectively. RESULTS: Thirty-two patients with AD, 32 patients with aMCI, and 32 cognitively normal people were enrolled. The severity of periodontitis was significantly increased in AD patients compared with aMCI patients and cognitively normal people. The 16S rRNA gene sequencing results showed that the relative abundances of 16 species in subgingival plaque were significantly correlated with cognitive function, and LC-MS/MS analysis identified a total of 165 differentially abundant metabolites in GCF. Moreover, multiomics Data Integration Analysis for Biomarker discovery using Latent cOmponents (DIABLO) analysis revealed that 19 differentially abundant metabolites were significantly correlated with Veillonella parvula, Dialister pneumosintes, Leptotrichia buccalis, Pseudoleptotrichia goodfellowii, and Actinomyces massiliensis, in which galactinol, sn-glycerol 3-phosphoethanolamine, D-mannitol, 1 h-indole-1-pentanoic acid, 3-(1-naphthalenylcarbonyl)- and L-iditol yielded satisfactory accuracy for the predictive diagnosis of AD progression. CONCLUSIONS: This is the first combined subgingival microbiome and GCF metabolome study in patients with AD and aMCI, which revealed that periodontal microbial dysbiosis and metabolic disorders may be involved in the etiology and progression of AD, and the differential abundance of the microbiota and metabolites may be useful as potential markers for AD in the future.

Experiment 1


Reviewed Marked as Reviewed by Svetlana up on 2024-6-14

Curated date: 2024/03/23

Curator: Aananditaa

Revision editor(s): Aananditaa, 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
Subgingival dental plaque Subgingival plaque,Subgingival dental plaque,subgingival dental plaque
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 (CN) and amnestic mild cognitive impairment (aMCI)
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
Patients with Alzheimer’s Disease (AD) dementia who were diagnosed following the National Institute on Aging and Alzheimer’s Association guidelines for probable AD dementia with the support of magnetic resonance imaging
Group 0 sample size Number of subjects in the control (unexposed) group
64
Group 1 sample size Number of subjects in the case (exposed) group
32
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
3 months

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
Not specified
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
PacBio RS

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)?
Yes
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
2

Alpha Diversity

Pielou Quantifies how equal the community is numerically
unchanged
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
Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
unchanged

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-6-14

Curated date: 2024/03/23

Curator: Aananditaa

Revision editor(s): Aananditaa, Scholastica

Source: Figure 1f

Description: LEfSe analysis revealed significant bacterial differences in subgingival microbiota among the cognitively normal (CN), amnestic mild cognitive impairment (aMCI), and Alzheimer’s Disease (AD) groups

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

NCBI Quality ControlLinks
Bacillota
Negativicutes
Prevotella
Veillonellales
Veillonellaceae
Prevotellaceae
Veillonella
Veillonella parvula
Fusobacteriaceae
Fusobacterium
Fusobacterium nucleatum
Prevotella denticola
Pseudomonas
Pseudomonadales
Pseudomonadaceae
Prevotella melaninogenica
Streptococcus mutans
Campylobacter gracilis
Streptococcus oralis
Afipia
Anaeroglobus
Anaeroglobus geminatus
Streptococcus anginosus
Afipia genosp. 6
Alphaproteobacteria
Methylorubrum
Coriobacteriales
Coriobacteriia
Atopobiaceae
Hyphomicrobiales
Mycoplasmopsis lipophila
Mycoplasmopsis
Megasphaera
Megasphaera micronuciformis
Bradyrhizobium
Nitrobacteraceae
Segatella oulorum
Lancefieldella
Acinetobacter pittii
Stomatobaculum
Stomatobaculum longum
Methylobacteriaceae
Lancefieldella rimae
Lancefieldella parvula
Treponema amylovorum
Selenomonas flueggei
Lactobacillaceae
Eubacteriaceae
Streptococcus salivarius
Steroidobacter
Steroidobacteraceae
Nevskiales

Revision editor(s): Aananditaa, Scholastica

Experiment 2


Reviewed Marked as Reviewed by Svetlana up on 2024-6-14

Curated date: 2024/03/23

Curator: Aananditaa

Revision editor(s): Aananditaa, Scholastica

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Cognitively normal (CN) and Alzheimer’s Disease (AD)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Amnestic mild cognitive impairment (aMCI)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with aMCI who met the previously published National Institute on Aging and Alzheimer’s Association criteria (2011) for “MCI due to AD,” with memory deficits as the only complaint of cognitive impairment.

Lab analysis

Statistical Analysis

Alpha Diversity

Pielou Quantifies how equal the community is numerically
unchanged
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
Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
unchanged

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-6-14

Curated date: 2024/03/23

Curator: Aananditaa

Revision editor(s): Aananditaa, Scholastica

Source: Figure 1f

Description: LEfSe analysis revealed significant bacterial differences in subgingival microbiota among the cognitively normal (CN), amnestic mild cognitive impairment (aMCI), and Alzheimer’s Disease (AD) groups

Abundance in Group 1: increased abundance in Amnestic mild cognitive impairment (aMCI)

NCBI Quality ControlLinks
Betaproteobacteria
Neisseriaceae
Neisseria
Neisseriales
Neisseria elongata
Rothia dentocariosa
Micrococcaceae
Rothia
Micrococcales
Capnocytophaga ochracea
Ralstonia pickettii
Ralstonia
Bacillales
Corynebacterium durum
Kingella denitrificans
Rothia mucilaginosa
Streptococcus parasanguinis
Haemophilus haemolyticus
Caulobacteraceae
Caulobacterales
Caulobacter
Caulobacter segnis

Revision editor(s): Aananditaa, Scholastica

Experiment 3


Reviewed Marked as Reviewed by Svetlana up on 2024-6-14

Curated date: 2024/03/23

Curator: Aananditaa

Revision editor(s): Aananditaa, Scholastica

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Cognitively normal (CN)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Alzheimer’s Disease (AD) and Amnestic mild cognitive impairment (aMCI)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with AD dementia who were diagnosed following the National Institute on Aging and Alzheimer’s Association guidelines for probable AD dementia with the support of magnetic resonance imaging and all patients with aMCI who met the previously published National Institute on Aging and Alzheimer’s Association criteria (2011) for “MCI due to AD,” with memory deficits as the only complaint of cognitive impairment.
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
64

Lab analysis

Statistical Analysis

Alpha Diversity

Pielou Quantifies how equal the community is numerically
unchanged
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
Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample
unchanged

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-6-14

Curated date: 2024/03/23

Curator: Aananditaa

Revision editor(s): Aananditaa, Scholastica

Source: Figure 1f

Description: LEfSe analysis revealed significant bacterial differences in subgingival microbiota among the cognitively normal (CN), amnestic mild cognitive impairment (aMCI), and Alzheimer’s Disease (AD) groups

Abundance in Group 1: decreased abundance in Alzheimer’s Disease (AD) and Amnestic mild cognitive impairment (aMCI)

NCBI Quality ControlLinks
Burkholderiales
Pasteurellaceae
Pasteurellales
Comamonadaceae
Escherichia coli
Escherichia
Neisseria subflava
Haemophilus parainfluenzae
Haemophilus
Leptotrichia buccalis
Rhodococcus
Propionibacteriales
Propionibacteriaceae
Rhodococcus qingshengii
Arachnia
Nocardiaceae
Streptococcus sanguinis
Arachnia propionica
Campylobacter showae
Capnocytophaga sputigena
Arachnia rubra
Weeksellaceae
Bergeyella
Peptoanaerobacter
Actinomyces massiliensis
Bergeyella cardium
Catonella
Catonella morbi
Johnsonella ignava
Pseudoleptotrichia goodfellowii
Pseudoleptotrichia

Revision editor(s): Aananditaa, Scholastica