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

Study information

Needs review

study design

cross-sectional observational, not case-control

Citation

PMID PubMed identifier for scientific articles.

38373985

DOI Digital object identifier for electronic documents.

https://doi.org/10.1186/s13195-024-01402-1

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

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Curated date: 2024/03/23

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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: Lower first secondary molar tooth , Upper first secondary molar tooth , Lower first secondary premolar tooth , Upper first secondary premolar tooth , Central incisor tooth Lower first permanent molar tooth,Mandibular first secondary molar tooth,Lower first secondary molar tooth,lower first secondary molar tooth,Maxillary first secondary molar tooth,Upper first permanent molar tooth,Upper first secondary molar tooth,upper first secondary molar tooth,Lower first permanent premolar tooth,Mandibular first secondary premolar tooth,Permanent first lower premolar tooth,Secondary first lower premolar tooth,Lower first secondary premolar tooth,lower first secondary premolar tooth,Maxillary first secondary premolar tooth,Permanent first upper premolar tooth,Secondary first upper premolar tooth,Upper first permanent premolar tooth,Upper first secondary premolar tooth,upper first secondary premolar tooth,Central incisor,Central incisor tooth,central incisor tooth

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 people

Group 1 name Corresponds to the case (exposed) group for case-control studies: Patients with AD dementia

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

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: 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: Non-quantitative PCR, 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

Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample: unchanged

Signature 1

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Source: Figure 3

Description: Relative abundances of candidate microbial biomarkers. Taxon abundances at the species level were statistically compared in group 0 and group 1

Abundance in Group 1: increased abundance in Patients with AD dementia

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Dialister pneumosintes
Veillonella parvula

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Signature 2

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Source: Figure 3

Description:

Abundance in Group 1: decreased abundance in Patients with AD dementia

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Actinomyces massiliensis
Leptotrichia buccalis
Pseudoleptotrichia goodfellowii

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Experiment 2

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Subjects

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology: Lower first secondary molar tooth , Lower first secondary premolar tooth , Upper first secondary molar tooth , Central incisor tooth , Upper first secondary premolar tooth Lower first permanent molar tooth,Mandibular first secondary molar tooth,Lower first secondary molar tooth,lower first secondary molar tooth,Lower first permanent premolar tooth,Mandibular first secondary premolar tooth,Permanent first lower premolar tooth,Secondary first lower premolar tooth,Lower first secondary premolar tooth,lower first secondary premolar tooth,Maxillary first secondary molar tooth,Upper first permanent molar tooth,Upper first secondary molar tooth,upper first secondary molar tooth,Central incisor,Central incisor tooth,central incisor tooth,Maxillary first secondary premolar tooth,Permanent first upper premolar tooth,Secondary first upper premolar tooth,Upper first permanent premolar tooth,Upper first secondary premolar tooth,upper first secondary premolar tooth

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Not specified

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Alzheimer’s disease

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

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: PacBio RS, RT-qPCR

Statistical Analysis

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?: Not specified

LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool: Not specified

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

Faith Phylogenetic diversity, takes into account phylogenetic distance of all taxa identified in a sample: unchanged

Signature 1

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Mark reviewed

Your review change was submitted

Needs review

Curated date: 2024/03/23

Curator: Aananditaa

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Source: Figure 3

Description:

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

NCBI	Quality Control	Links
Actinomyces massiliensis
Leptotrichia buccalis

Revision editor(s): Aananditaa

Experiment 3

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Mark reviewed

Your review change was submittedDuplicate this Experiment Add a new Signature

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Curated date: 2024/03/23

Curator: Aananditaa

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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: Central incisor tooth , Upper first secondary molar tooth , Upper first secondary premolar tooth , Lower first secondary molar tooth , Lower first secondary premolar tooth Central incisor,Central incisor tooth,central incisor tooth,Maxillary first secondary molar tooth,Upper first permanent molar tooth,Upper first secondary molar tooth,upper first secondary molar tooth,Maxillary first secondary premolar tooth,Permanent first upper premolar tooth,Secondary first upper premolar tooth,Upper first permanent premolar tooth,Upper first secondary premolar tooth,upper first secondary premolar tooth,Lower first permanent molar tooth,Mandibular first secondary molar tooth,Lower first secondary molar tooth,lower first secondary molar tooth,Lower first permanent premolar tooth,Mandibular first secondary premolar tooth,Permanent first lower premolar tooth,Secondary first lower premolar tooth,Lower first secondary premolar tooth,lower first secondary premolar tooth

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Cognitively normal people

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Not specified

Sequencing type: Not specified

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Not specified

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: Not specified