Exploring the Gut-Brain Connection: The Role of Microbiota in Alzheimer’s Disease Pathogenesis

Feb 9, 2026Dementia and neurocognitive disorders

The Gut Microbiome's Role in Developing Alzheimer's Disease

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Abstract

Alzheimer's disease accounts for 60% to 70% of dementia cases worldwide.

The microbiota-gut-brain axis is implicated in the progression of Alzheimer's disease through complex signaling pathways.
Oral and gut microbial populations produce neurotransmitters and neuroactive metabolites that influence brain function.
Imbalances in oral and gut microbiota may lead to systemic inflammation, which is associated with the formation of amyloid-β plaques and tau-related changes in Alzheimer's disease.
A new therapeutic model involving probiotics, prebiotics, synbiotics, and postbiotics aims to restore microbial balance and improve cognitive function.
Emerging findings suggest microbiota-targeted therapies could affect the course of Alzheimer's disease, although limitations exist.

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Alzheimer's disease (AD), the primary cause of dementia accounting for 60% to 70% of cases globally, results in a gradual decline in cognitive abilities, affecting memory, executive function, and daily activities. Recent research highlights the essential involvement of the microbiota-gut-brain axis in AD pathogenesis, characterized by complex bidirectional signaling that modulates neuroinflammation, neurogenesis, neurotransmission, and immune functions. This manuscript extends the discussion beyond the gut alone by emphasizing the significance of the oral-gut microbiota axis as a dynamic and relatively under-investigated factor in AD progression. Microbial populations in both the oral cavity and gastrointestinal tract produce key neurotransmitters, such as gamma-aminobutyric acid, noradrenaline, and dopamine, as well as neuroactive metabolites like short-chain fatty acids, which together impact brain physiology. Disturbances in gut and oral microbial balance can compromise barrier integrity, promoting systemic inflammation and neuroinflammation, and facilitating amyloid-β plaque formation and tau-related changes typical of AD. This review introduces a novel probiotic, prebiotics, synbiotics, and postbiotics (PPSP) therapeutic model designed to modulate both oral and gut microbiota, aiming to restore homeostasis, regulate neuroimmune interactions, and counteract cognitive impairment. We comprehensively assess emerging clinical and translational findings supporting the effectiveness of microbiota-targeted therapies in the scope of this dual-axis framework, addressing both their potential to alter disease course and recognized limitations. By underscoring the importance of the integrated oral-gut microbiota axis alongside targeted PPSP interventions, this manuscript puts forth a paradigm-shifting conceptual strategy that may redefine approaches to AD management and improve cognitive outcomes.

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Exploring the Gut-Brain Connection: The Role of Microbiota in Alzheimer’s Disease Pathogenesis

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