Association Between Oral Microbiota Dysbiosis and the Risk of Dementia: A Systematic Review
Abstract
1. Introduction
1.1. The Role of the Apolipoprotein
1.2. Research Question
1.3. Objective
2. Materials and Methods
2.1. Study Design
2.2. Eligibility Criteria
2.2.1. Inclusion Criteria
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- Population: Older adults (≥50 years) with a dementia diagnosis.
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- Intervention: Evaluation of the oral microbiota using genetic sequencing methods, bacterial culture, metagenomics, quantitative PCR, or other molecular analyses.
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- Comparator: Individuals without a dementia diagnosis.
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- Outcome: Measurement of the association between oral dysbiosis and the risk of dementia, cognitive decline, or neuroinflammatory biomarkers.
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- Study Design: Observational studies (cohort, case–control, cross-sectional) analyzing the relationship between oral microbiota and dementia.
2.2.2. Exclusion Criteria
2.3. Search Strategy
2.4. Study Selection
2.5. Data Extraction
2.6. Risk of Bias Assessment
2.7. Data Processing
2.8. Ethical Considerations
3. Results
3.1. Summary of Study Designs and Their Impact on Research Robustness
3.1.1. Cross-Sectional Observational Studies (n = 6)
Author/ Year | Country | N | n with CI * | n Without CI | Age Range | Type of CI Evaluated/ Stage, Grade | Neuropsychological Scales | Oral Microbiota Assessment Method | Sample Type | Bacteria Associated with Dysbiosis (Increase) | Bacteria Associated with Dysbiosis (Reduction) | Outcomes |
---|---|---|---|---|---|---|---|---|---|---|---|---|
Babenia [21] 2023 | Ukraine | 27 | 27 | No age range or average age is specified. | Alzheimer’s/ it does not specify differentiated clinical stages or RDA or MMSE values. | Not reported | Polymerase chain reaction (PCR) | Gingival fluid from periodontal pockets | Tannerella forsythia, Fusobacterium nucleatum, Aggregatibacter actinomycetemcomitans | Porphyromonas gingivalis | Tannerella forsythia and Fusobacterium nucleatum were detected in 100% of Alzheimer’s patients. The microbial composition suggests a possible link between oral dysbiosis and dementia pathogenesis. | |
Bathini [22] 2020 | Switzerland | 80 | 38 | 42 | CNh: 67.0 ± 9.2 years CNr: 68.1 ± 10.0 years MCI: 73.2 ± 8.1 years AD: 71.1 ± 6.6 years | Alzheimer’s/ inclusion of patients in moderate-severe phase of AD. | Mini-Mental State Exam (MMSE), Clinical Dementia Rating (CDR), University of Pennsylvania Smell Identification Test (UPSIT) CNh (cognitively normal healthy): MMSE ≈ 28.4; CDR ≈ 0.0 CNr (cognitively normal at risk): MMSE ≈ 28.4; CDR ≈ 0.1 MCI: MMSE ≈ 22.5; CDR ≈ 0.8 AD: MMSE ≈ 14.2; CDR ≈ 1.4 | 16S rRNA Sequencing (Illumina MiSeq) | Saliva | Leptotrichia wadei (MCI), Cardiobacterium valvarum (AD) | Filifactor villosus, Filifactor alocis, Prevotella tannerae (MCI y AD), Porphyromonas gingivalis (MCI) | The salivary microbiota presents specific changes depending on the stage of dementia, with a reduction in periodontal bacteria and an increase in opportunistic species in the progression of the disease. |
Chen [23] 2022 | China | 66 | 66 | 82.85 ± 6.00 years | All patients were diagnosed with mild Alzheimer’s disease | Mini-Mental State Examination (MMSE), Neuropsychiatric Inventory (NPI), Nursing Home Adjustment Scale (NHAS), Alzheimer’s Disease Cooperative Study-ADL (ADCS-ADL), Kayser-Jones Brief Oral Health Status Examination (BOHSE) | 16S rRNA Sequencing (Illumina MiSeq) | Subgingival biofilm | Alphaproteobacteria, Betaproteobacteria, Flavobacteria | Actinobacteria, Spirochaete, Synergistetes | The oral health intervention improved the oral microbiota and reduced cognitive impairment in patients with mild Alzheimer’s after 6 months of follow-up. | |
Chen [24] 2024 | China | 165 | 125 | 40 | Normal controls: 67.45 ± 8.36 years SCD: 66.90 ± 7.98 years MCI: 66.33 ± 8.83 years Dementia: 68.44 ± 6.71 years | It does not report specific data on stage or severity, it only compares individuals with Alzheimer’s. | Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) | 16S rRNA Sequencing (Illumina MiSeq) | Subgingival biofilm | Porphyromonas, Prevotella, Fusobacterium, Leptotrichia, Campylobacter, Selenomonas | Capnocytophaga, Saccharibacteria_genera_incertae_sedis, Lautropia, Granulicatella | Subgingival microbial composition is associated with different levels of cognitive function, suggesting a possible use as a biomarker of cognitive decline. |
Da [25] 2023 | China | 94 | 47 | 47 | Not explicitly reported. | No classification is specified in degrees of severity; it is only reported as Alzheimer’s or MCI vs. controls. | Mini-Mental State Examination (MMSE), Auditory Verbal Learning Test, Trail-Making Test, RMB (Renminbi) Test | 16S rDNA Sequencing (Illumina MiSeq) | Unstimulated saliva | Veillonella unclassified_Veillonella, Fusobacterium sp._HMT_203 | Gemella haemolysans, Streptococcus gordonii | Older adults with mild cognitive impairment have an altered oral microbial composition compared to cognitively normal individuals. Gemella haemolysans and Streptococcus gordonii may be potential indicators of MCI. |
Golipoor [27] 2024 | Iran | 152 | 76 | 76 | AD: 87.96 ± 7.91 years Non-AD: 85.18 ± 5.79 years | Alzheimer’s/ preclinical. Very mild cognitive decline/ mild to moderate cognitive decline and severe dementia. | Global Deterioration Scale (GDS) | Fungal culture on agar Sabouraud Chloramphenicol and PCR-Sequencing | Oral mucus swab | Candida albicans (AD: 80%, No AD: 40%), Candida glabrata (AD: 9%) | Increased fungal diversity in individuals without AD | Patients with AD have a higher prevalence of Candida spp. and a lower fungal diversity in the oral microbiota. Fungal microbiota analysis could be an early marker of the disease. |
L’Heureux [14] 2025 | United Kingdom | 115 | 55 | 60 | Inclusion criteria: ≥50 years old. No mean age is reported. | Patients were classified as mild cognitive impairment (MCI). Patients with clinical Alzheimer’s were not included. | Mini-Mental State Examination (MMSE), Switching Stroop, Trail Making, Digit Span | 16S rRNA sequencing | Mouth rinse | Porphyromonas (MCI), Prevotella intermedia (APOE4+) | Neisseria, Haemophilus (associated with better cognition) | The oral microbiome of people with MCI exhibits a higher abundance of Porphyromonas and a lower level of Neisseria and Haemophilus, suggesting a link between oral dysbiosis and cognitive decline. |
Liu [26] 2019 | China | 78 | 39 | 39 | The average age is not specified. | Alzheimer’s | Mini-Mental State Examination (MMSE), Neuropsychiatric Inventory (NPI), Clinical Dementia Rating (CDR), Activity of Daily Living Scale (ADL) | 16S rRNA sequencing | Unstimulated saliva | Moraxella, Leptotrichia, Sphaerochaeta | Rothia | Patients with AD have lower salivary microbial diversity and alterations in bacterial composition, with an increase in Moraxella and a reduction in Rothia. |
Sritana [17] 2024 | Thailand | 100 | 56 | 44 | AD: 66.90 ± 7.06 years MCI: 68.50 ± 6.35 years Controls: 64.73 ± 4.78 years | Alzheimer’s/ average values are reported for AD patients. | Clinical Dementia Rating (CDR), Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE) | 16S rRNA Sequencing (PacBio SMRT) | Saliva | Fusobacteriota, Peptostreptococcaceae | Veillonella | Patients with AD show greater diversity of oral microbiota and elevated levels of Fusobacteriota and Peptostreptococcaceae, suggesting a possible role in the pathogenesis of the disease. |
3.1.2. Case–Control Studies (n = 2)
3.1.3. Randomized Controlled Trial (n = 1)
4. Discussion
4.1. Proposed Scheme on How Oral Microbial Dysbiosis May Influence the Development of Dementia
4.2. Limitations of the Study
5. Conclusions
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
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Database | Formulation | Filters |
---|---|---|
Pubmed | ((“Oral microbiome” [Title/Abstract] OR “oral microbiota” [Title/Abstract] OR “oral bacteria” [Title/Abstract] OR “oral dysbiosis” [Title/Abstract]) AND (“Dementia” [Title/Abstract] OR “cognitive decline” [Title/Abstract] OR “Alzheimer’s disease” [Title/Abstract] OR “neurodegeneration” [Title/Abstract] OR “mild cognitive impairment” [Title/Abstract])) OR ((“Microbiota” [MeSH Terms] OR “Oral microbiome” [MeSH Terms] OR “Bacteria” [MeSH Terms]) AND (“Dementia” [MeSH Terms] OR “Alzheimer Disease” [MeSH Terms] OR “Neurodegenerative Diseases” [MeSH Terms])) | Clinical Study, Clinical Trial, Randomized Controlled Trial. |
Scopus | (TITLE-ABS-KEY (“oral microbiome” OR “oral microbiota” OR “oral bacteria” OR “oral dysbiosis” OR “oral microbial community” OR “oral flora” OR “oral microbial diversity” OR “oral microbial ecosystem” OR “oral microbial composition” OR “oral microbiological profile” OR “oral pathogens” OR “oral microorganisms” OR “microbiota” OR “bacteria”) AND TITLE-ABS-KEY (“dementia” OR “cognitive decline” OR “Alzheimer’s disease” OR “neurodegeneration” OR “mild cognitive impairment” OR “neurocognitive disorders” OR “cognitive dysfunction” OR “neurodegenerative diseases” OR “cognitive disorders” OR “brain aging”)) | AND (LIMIT-TO (DOCTYPE, “ar”)) |
WoS | (TS = (“oral microbiome” OR “oral microbiota” OR “oral bacteria” OR “oral dysbiosis” OR “oral microbial community” OR “oral flora” OR “oral microbial diversity” OR “oral microbial ecosystem” OR “oral microbial composition” OR “oral microbiological profile” OR “oral pathogens” OR “oral microorganisms” OR “microbiota” OR “bacteria”) AND TS = (“dementia” OR “cognitive decline” OR “Alzheimer’s disease” OR “neurodegeneration” OR “mild cognitive impairment” OR “neurocognitive disorders” OR “cognitive dysfunction” OR “neurodegenerative diseases” OR “cognitive disorders” OR “brain aging” OR “cognitive impairment”)) | Refined By:Document Types: Article |
Embase | (‘oral microbiome’: ti,ab,kw OR ‘oral microbiota’: ti,ab,kw OR ‘oral bacteria’: ti,ab,kw OR ‘oral dysbiosis’: ti,ab,kw) AND (dementia: ti,ab,kw OR ‘cognitive decline’: ti,ab,kw OR ‘alzheimers disease’: ti,ab,kw OR neurodegeneration: ti,ab,kw OR ‘mild cognitive impairment’: ti,ab,kw) | |
Cochrane Library | (“Oral microbiome” OR “oral microbiota” OR “oral bacteria” OR “oral dysbiosis”): ti,ab,kw AND (“Dementia” OR “cognitive decline” OR “Alzheimer’s disease” OR “neurodegeneration” OR “mild cognitive impairment”): ti,ab,kw (Word variations have been searched) |
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Chaple-Gil, A.M.; Santiesteban-Velázquez, M.; Urbizo Vélez, J.J. Association Between Oral Microbiota Dysbiosis and the Risk of Dementia: A Systematic Review. Dent. J. 2025, 13, 227. https://doi.org/10.3390/dj13060227
Chaple-Gil AM, Santiesteban-Velázquez M, Urbizo Vélez JJ. Association Between Oral Microbiota Dysbiosis and the Risk of Dementia: A Systematic Review. Dentistry Journal. 2025; 13(6):227. https://doi.org/10.3390/dj13060227
Chicago/Turabian StyleChaple-Gil, Alain Manuel, Meylin Santiesteban-Velázquez, and Joaquín Juan Urbizo Vélez. 2025. "Association Between Oral Microbiota Dysbiosis and the Risk of Dementia: A Systematic Review" Dentistry Journal 13, no. 6: 227. https://doi.org/10.3390/dj13060227
APA StyleChaple-Gil, A. M., Santiesteban-Velázquez, M., & Urbizo Vélez, J. J. (2025). Association Between Oral Microbiota Dysbiosis and the Risk of Dementia: A Systematic Review. Dentistry Journal, 13(6), 227. https://doi.org/10.3390/dj13060227