The Oral–Brain Axis: The Role of the Oral Microbiome in Neurodegenerative Pathology

Samim S. M. Baker; Sura Hameed Mohammed

doi:10.59675/

Authors

Samim S. M. Baker College of Dentistry, Al Bayt University, Karbala, 56001, Iraq Author
Sura Hameed Mohammed Medical Microbiology & Immunology, College of Dentistry, Ahl al-Bayt University, Iraq. Author

DOI:

https://doi.org/10.59675/

Abstract

Background: The oral microbiome interacts with the nervous system, which may link it to neurodegenerative processes. Oral microbial dysbiosis, periodontal inflammation, and cognitive impairment/neurodegenerative diseases are related, but the biological mechanisms and causal relationships remain unclear.

Objectives: To review the available evidence for understanding the connection between the oral microbiome and periodontal pathogenic species, and their link with neurodegenerative pathological conditions in general and Alzheimer's disease (AD) and Parkinson's disease (PD) in particular, and to discuss the potential biological pathways and therapeutic implications.

Methods: A structured narrative literature search was conducted mostly in PubMed/MEDLINE from 2017–2026. We conducted broad and targeted searches on the oral microbiome and periodontal disease in the context of neurodegeneration, neuroinflammation, blood–brain barrier (BBB) dysfunction, Alzheimer’s disease (AD), periodontal disease (PD), and specific periodontal pathogens and virulence factors. We considered primary human studies, animal studies, and in vitro mechanistic studies, along with relevant review articles. We then summarized the evidence by theme and categorized it by study design, biological plausibility, consistency of findings, and major methodological limitations.

Results: These epidemiological studies are mostly supportive of the hypothesis that periodontal disease is linked with cognitive impairment or dementia, but there are important residual confounding and reverse causation issues to consider. Experimental studies have demonstrated neuroinflammation, BBB dysfunction, and altered amyloid-β and tau-related pathology in the brain. This pathogen-specific mechanistic evidence exists for Porphyromonas gingivalis and its gingipains. Furthermore, Treponema denticola and Fusobacterium (Fusobacterium) nucleatum have been demonstrated to cause neuroinflammatory and neurodegenerative effects in experimental models. Studies of the human oral microbiome in AD and PD show disruption of the microbial community. Still, findings are inconsistent, and no microbial signature for AD or PD has been identified. Evidence for PD is relatively limited.

Conclusion: Available evidence suggests a biologically plausible oral–brain axis by which the inflammatory state of the gums and oral microbial products could impact the neurodegenerative processes. However, there isn’t enough human evidence to prove causality, and much of the mechanistic evidence comes from experimental models. Therefore, it is suggested that oral dysbiosis and periodontal disease should be viewed as a possible modifiable risk factor for neurodegenerative disease, and not as an actual causative disease. Longitudinal human studies and well-designed clinical trials are required to assess the effect of periodontal health and/or the oral microbiome on the risk and/or progression of neurodegenerative disease.

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