From systemic to oral: Unifying immunological mechanisms via the gut microbiome axis

While the gut microbiome regulates host homeostasis and systemic disease via the gut-immune axis, its potential role in regulating oral diseases remains underexplored. This review examines how established gut microbiome-immune mechanisms may contribute to oral inflammation and their therapeutic potential. Gut microbiome dysbiosis may influence oral diseases through microbial metabolites, intestinal barrier dysfunction, inflammatory signaling, and immune regulation. Evidence from systemic diseases supports these mechanisms and provides a rationale for microbiome-targeted approaches, including probiotics, dietary interventions, and fecal microbiota transplantation. However, direct clinical evidence in oral diseases remains limited and heterogeneous. Future research should clarify bidirectional gut-oral interactions, standardize microbiome assessment and clinical outcomes. Well-designed clinical studies are needed to address these limitations and translate the gut-oral axis into meaningful interventions.