Of mice and men—The emerging oral–gut–brain axis of health and disease

OBJECTIVES: Oral health's inextricable links to systemic health are highlighted by the emerging oral-gut-brain axis and other well-known axes. There is growing evidence of a complex oral-gut-brain axis linking mouth and gut microbiomes with the central nervous system. Axis disruptions, characterized as oral and gut dysbiosis or microbial imbalances, can trigger oral and systemic inflammation and neuroinflammation, contributing to diseases such as Alzheimer's disease and Parkinson's disease. MATERIALS AND METHODS: We summarize the oral-gut-brain axis mechanistic pathways, key evidence from human clinical and animal studies, and how the oral microbiome modulates human health and disease. RESULTS: Periodontal disease (PD) is associated with increased oral pathogen presence in diseased tissues throughout the human body. Preclinical models recapitulate these findings. Experimental periodontal infection induces dysbiosis that is linked to activation of inflammatory pathways that promote diseased phenotypes. Novel therapeutic approaches, including the probiotic fbacteriocin nisin, are increasingly recognized for targeted microbiome therapy at multiple inflection points across the axis. Nisin restores microbial balance, reduces inflammation, inhibits end-organ pathology, prevents periodontal bone loss, and reduces brain amyloid/tau accumulation and cytokine expression. CONCLUSIONS: These findings highlight the complexity of the oral-gut-brain axis and the ability to modulate the axis using bacteriocin-based approaches. CLINICAL RELEVANCE: Future probiotic or antimicrobial strategies aimed at ameliorating neuroinflammatory and metabolic diseases via microbiome-targeted therapy hold clinical promise.