The oral microbiome-redox-inflammation axis in neurodegeneration: mechanistic insights and therapeutic perspectives

The oral microbiome is a highly diverse and metabolically active ecosystem that plays a pivotal role in maintaining oral and systemic homeostasis. Disruption of this balance, referred to as oral dysbiosis, has been increasingly implicated in the pathogenesis of neurodegenerative diseases (NDs) such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). Although the precise molecular mechanisms remain incompletely defined, accumulating evidence indicates that oxidative stress and redox signaling act as central mediators linking microbial imbalance to neuroinflammatory responses and progressive neuronal dysfunction. In this review, we critically synthesize interdisciplinary findings on the oral microbiome-brain axis, emphasizing redox-sensitive pathways that mediate communication between oral pathogens and the central nervous system. We discuss how reactive oxygen species (ROS), generated by microbial metabolites and pathogen-associated molecular patterns, activate various signaling cascades, thereby exacerbating neuroinflammation and glial activation. We further evaluate evidence that oral dysbiosis contributes to blood-brain barrier (BBB) disruption, peripheral immune priming, and chronic neuroimmune dysregulation. By integrating mechanistic, cellular, and clinical perspectives, we identify oxidative stress and redox signaling as critical biological bridges between oral dysbiosis and neurodegeneration. This framework highlights not only the translational potential of targeting redox pathways and the oral microbiome for preventive and therapeutic strategies but also the need for future research to clarify causal relationships and validate clinical applications.