Classifying dementia progression using microbial profiling of saliva

Study information

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study design

cross-sectional observational, not case-control

Citation

PMID PubMed identifier for scientific articles.

32775594

DOI Digital object identifier for electronic documents.

10.1002/dad2.12000

URI

Authors

Bathini P, Foucras S, Dupanloup I, Imeri H, Perna A, Berruex JL, Doucey MA, Annoni JM, Auber Alberi L

Journal

Alzheimer's & dementia (Amsterdam, Netherlands)

Year

2020

Keywords:

Alzheimer's disease, cytokines, olfaction, oral microbiome

INTRODUCTION: There is increasing evidence linking periodontal infections to Alzheimer's disease (AD). Saliva sampling can reveal information about the host and pathogen interactions that can inform about physiological and pathological brain states. METHODS: A cross-sectional cohort of age-matched participants (78) was segmented according to their chemosensory (University of Pennsylvania Smell Identification Test; UPSIT) and cognitive scores (Mini-Mental State Exam; MMSE and clinical dementia rating; CDR). Mid-morning saliva was sampled from each participant and processed for microbiome composition and cytokine analysis. Linear discriminant analysis (LDA) was used to unravel specific changes in microbial and immunological signatures and logistic regression analysis (LRA) was employed to identify taxa that varied in abundance among patient groups. RESULTS: Using olfaction we distinguish in the cognitively normal population a segment with high chemosensory scores (CNh, 27) and another segment with chemosensory scores (CNr, 16) as low as mild cognitive impairment (MCI, 21) but higher than the AD group (17). We could identify stage-specific microbial signatures changes but no clearly distinct cytokine profiles. Periodontal pathogen species as Filifactor villosus decline with the increasing severity of AD, whereas opportunistic oral bacteria such as Leptotrichia wadei show a significant enrichment in MCI. CONCLUSIONS: The salivary microbiome indicates stage-dependent changes in oral bacteria favoring opportunistic species at the expense of periodontal bacteria, whereas the inflammatory profiles remain mainly unchanged in the sampled population.

Experiment 1

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Subjects

Location of subjects

Switzerland

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

Saliva Sailva normalis,Saliva atomaris,Saliva molecularis,Salivary gland secretion,Saliva,saliva

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 Healthy (CNh)

Group 1 name Corresponds to the case (exposed) group for case-control studies

Cognitively Normal at risk (CNr)

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

Cognitively normal people with hyposmia

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

27

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

15

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

ANOVA

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

Signature 1

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Source: Figure 1C

Description: Significantly different bacterial taxa in CNr and CNh

Abundance in Group 1: increased abundance in Cognitively Normal at risk (CNr)

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Leptotrichia wadei

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Source: Figure 2

Description: Significantly different bacterial taxa in CNr and CNh

Abundance in Group 1: decreased abundance in Cognitively Normal at risk (CNr)

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Filifactor villosus

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Experiment 2

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Subjects

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

Patients with Mild Cognitive Impairment (MCI)

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

21

Lab analysis

Statistical Analysis

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Source: Figure 1C

Description: Significantly different bacterial taxa in MCI and CNh

Abundance in Group 1: increased abundance in Mild Cognitive Impairment (MCI)

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Leptotrichia wadei

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Source: Figure 1C

Description: Significantly different bacterial taxa in MCI and CNh

Abundance in Group 1: decreased abundance in Mild Cognitive Impairment (MCI)

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Filifactor villosus

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Experiment 3

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Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies

Alzheimer's Disease (AD) patients

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

Patients with Alzheimer's Disease

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

17

Lab analysis

Statistical Analysis

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Source: Figure 1C

Description: Significantly different bacterial taxa in CAD patients and CNh

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

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Filifactor villosus
Leptotrichia wadei

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Experiment 4

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Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies

Cognitively Normal at risk (CNr)

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

Cognitively normal people with hyposmia

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

15

Lab analysis

Statistical Analysis

Statistical test

Mann-Whitney (Wilcoxon)

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Source: Figure 1D + Figure 1E

Description: Significantly different bacterial taxa in CNr and CNh

Abundance in Group 1: decreased abundance in Cognitively Normal at risk (CNr)

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Alloprevotella tannerae
Porphyromonas gingivalis
Filifactor alocis
Cardiobacterium valvarum

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Experiment 5

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Subjects

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

Patients with Mild Cognitive Impairment (MCI)

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

21

Lab analysis

Statistical Analysis

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Source: Figure 1D + Figure 1E

Description: Significantly different bacterial taxa in MCI and CNh

Abundance in Group 1: increased abundance in Mild Cognitive Impairment (MCI)

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Cardiobacterium valvarum

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Signature 2

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Source: Figure 1D + Figure 1E

Description: Significantly different bacterial taxa in MCI and CNh

Abundance in Group 1: decreased abundance in Mild Cognitive Impairment (MCI)

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Porphyromonas gingivalis
Alloprevotella tannerae
Filifactor alocis

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Experiment 6

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Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies

Alzheimer's Disease (AD) patients

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

Patients with Alzheimer's Disease

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

17

Lab analysis

Statistical Analysis

Signature 1

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Source: Figure 1D + Figure 1E

Description: Significantly different bacterial taxa in AD patients and CNh

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

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Cardiobacterium valvarum

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Source: Figure 1D + Figure 1E

Description: Significantly different bacterial taxa in AD patients and CNh

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

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Porphyromonas gingivalis
Alloprevotella tannerae
Filifactor alocis

Revision editor(s): AaishahM

Experiment 7

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Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies

Cognitively Normal at risk (CNr)

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

Cognitively normal people with hyposmia

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

15

Lab analysis

Statistical Analysis

Statistical test

LEfSe

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

2.0

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Source: Figure S2A + Figure S2B

Description: Significantly different bacterial taxa in CNr and CNh

Abundance in Group 1: increased abundance in Cognitively Normal at risk (CNr)

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Calothrix
Leptotrichia hofstadii
Cyanophyceae
Rothia mucilaginosa

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Source: Figure S2A + Figure S2B

Description: Significantly different bacterial taxa in CNr and CNh

Abundance in Group 1: decreased abundance in Cognitively Normal at risk (CNr)

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Peptostreptococcaceae
Filifactor
Rhodothermus
Rhodothermus clarus

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Experiment 8

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Subjects

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

Patients with Mild Cognitive Impairment (MCI)

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

21

Lab analysis

Statistical Analysis

Signature 1

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Source: Figure S2C + Figure S2D

Description: Significantly different bacterial taxa in MCI and CNh

Abundance in Group 1: increased abundance in Mild Cognitive Impairment (MCI)

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Leptotrichia
Leptotrichiaceae
Fusobacteriales
Streptococcus mutans
Streptococcus troglodytae
Leptotrichia wadei
Fusobacteriia

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Source: Figure S2C + Figure S2D

Description: Significantly different bacterial taxa in MCI and CNh

Abundance in Group 1: decreased abundance in Mild Cognitive Impairment (MCI)

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Synergistales
Synergistaceae
Spirochaetaceae
Treponema
Treponema lecithinolyticum
Dialister
Erysipelothrix
Filifactor
Spirochaetia
Spirochaetales
Alloprevotella tannerae
Prevotella intermedia
Dialister invisus
Prevotella nigrescens
Synergistia
Synergistota
Synechococcales
Bacteroides xylanisolvens
Streptococcus intermedius
Filifactor villosus
Limosilactobacillus fermentum

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Experiment 9

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Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies

Alzheimer's Disease (AD) patients

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

Patients with Alzheimer's Disease

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

17

Lab analysis

Statistical Analysis

Signature 1

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Source: Figure S2E + Figure S2F

Description: Significantly different bacterial taxa in AD patients and CNh

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

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Aminiphilus
Calothrix
Kocuria
Cyanophyceae
Aminiphilus circumscriptus
Kocuria rosea
Streptococcus sobrinus

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Source: Figure S2E + Figure S2F

Description: Significantly different bacterial taxa in AD patients and CNh

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

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Spirochaetaceae
Treponema
Peptoniphilus methioninivorax
Spirochaetia
Spirochaetales
Alloprevotella tannerae
Filifactor villosus

Revision editor(s): AaishahM