The oral-gut-brain axis in periodontitis: microbial signaling in systemic and neuroinflammatory disease

Jan 15, 2026Brain research

How mouth and gut bacteria communicate in gum disease and related body and brain inflammation

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Abstract

Periodontitis is associated with the development of systemic and neurological disorders through complex interactions between oral health and the body's immune system.

Periodontal pathogens can disrupt local immune balance and may be transferred to the gut and brain.
This transfer can trigger systemic inflammation and neuroinflammation, potentially leading to diseases like Alzheimer's and Parkinson's.
Mechanisms involved include the spread of pathogens through the bloodstream, nerve pathways, and immune cell movement.
Oral dysbiosis may contribute to the activation of immune responses linked to neuroinflammation and neurodegeneration.
New diagnostic and therapeutic strategies, including precision medicine and microbiome remodeling, could improve intervention approaches.

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Periodontitis, a chronic inflammatory disease of the oral cavity, has been identified as a modifiable risk factor of the development of systemic and neurological disorders via a complicated interplay of microbiological, immunological, and neural interactions. Periodontal pathogens breach local immune homeostasis, are translocated to the gut and brain, and trigger a cascade of immune deregulation, leaky gut, and blood-brain barrier, thereby forming a tri-directional communication network that links local oral inflammation to systemic and neurovascular conditions. This review synthesizes existing evidence on how oral dysbiosis, can spread to the gut and trigger systemic inflammation, leading to neuroinflammation and neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. Mechanistically, the OGB axis acts through various processes, such as hematogenous spread, retrograde axonal transport, immune cell trafficking (Trojan horse mechanism), and extracellular vesicle-based signaling corresponding to the causes of neuroinflammation, microglial activation, and the pathology of tau and amyloid. The diagnostic and therapeutic implications of the OGB axis provide new pathways toward early intervention with precision medicine, microbiome remodeling, immune-based therapy, and neuroprotective approaches. Emerging technologies, including AI-based diagnostics and biosensing technologies, offers noninvasive tools to track host-microbial interactions and inflammatory biomarkers. This integrative view underscores the central importance of oral health in systemic homeostasis and the development of neurodegenerative conditions, necessitating collaborative approaches between dentistry, neurology, and immunology to cooperate to deliver efficacy in disease elimination and mitigation.

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The oral-gut-brain axis in periodontitis: microbial signaling in systemic and neuroinflammatory disease

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