From periodontitis to neurodegeneration: Can probiotics modulate the P. gingivalis –amyloid pathway in Alzheimer's disease?

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the gradual destruction of cognitive and behavioral functions. Despite the continuous research efforts, there is still no cure for this disease. In recent years, researchers have investigated Porphyromonas gingivalis (P. gingivalis) as a potential cause of AD. P. gingivalis-lipopolysaccharides (LPS) and gingipains have been implicated in neuroinflammatory cascades relevant to AD. The gut-brain axis provides a pathway for microbial migration, immune activation, and regulation of the central nervous system function. Emerging evidence suggests that selected probiotics may modulate these pathways by restoring microbial balance, reinforcing epithelial barrier function, and regulating innate and adaptive immunity. Importantly, much of the evidence and mechanistic support for these effects derives from preclinical and animal studies, whereas human data remain limited to associative findings and early-stage clinical trials. Early clinical trials report modest improvements in cognitive scores and systemic inflammatory markers. Strain selection, dose, and treatment duration make direct comparisons challenging. This review integrates the literature on the links between P. gingivalis and AD, suggesting that probiotics may be used as neuroprotective agents. Taken together, current preclinical signals are consistent with the potential of probiotics as feasible adjuncts, pending confirmatory trials with standardized formulations.