Oral pathogens meet the gut microbiome: new mechanistic insights on systemic disease

The oral-gut axis represents a critical bidirectional pathway linking oral microbiota to systemic health. Dysbiosis of the oral microbiome, driven by pathogens like Porphyromonas gingivalis, Fusobacterium nucleatum, Streptococcus species, and Helicobacter pylori, disrupts gut ecology via direct translocation, metabolite signaling (e.g., TMAO, SCFAs), and immune crosstalk (e.g., Th17). This leads to gut barrier dysfunction, systemic inflammation, and metabolic disturbances, contributing to diverse diseases beyond the oral cavity. Evidence supports causal links with conditions including rheumatoid arthritis, cardiovascular diseases, neurodegenerative disorders, metabolic syndrome, and gastrointestinal cancers. Emerging diagnostic tools exploit these oral pathogens as biomarkers for non-invasive disease detection. Therapeutic strategies, such as probiotics, dietary interventions, and periodontal therapy, target this axis to restore microbial homeostasis and ameliorate systemic inflammation. Future research must focus on longitudinal human studies and multi-omics approaches to elucidate mechanistic details and develop effective clinical interventions for preventing and managing systemic diseases linked to oral-gut microbial dysbiosis.