Porphyromonas gingivalis oral infection promotes atherosclerosis with suppression of the AhR/IDO pathway in ApoE −/− mice

BACKGROUND: Porphyromonas gingivalis (P. gingivalis) is implicated in atherosclerosis (AS) via inflammatory mechanisms. The aryl hydrocarbon receptor (AhR) exerts atheroprotective effects through the indoleamine 2,3-dioxygenase (IDO)-dependent kynurenine pathway, which modulates vascular inflammation. However, its role in P. gingivalis-induced AS remains unclear. METHODS: ) mice fed a high-fat diet and orally inoculated with P. gingivalis for 8 weeks. An AhR agonist was administered to modulate AhR/IDO signaling. Histopathological, molecular, and cytokine analyses were conducted to assess plaque formation, collagen deposition, inflammation, and endothelial function. The aortic microbial composition was evaluated by 16S rRNA sequencing. RESULTS: P. gingivalis infection suppressed AhR and IDO expression and activity in both serum and aorta. AhR activation reduced the atherosclerotic plaque area, collagen accumulation, and inflammatory cytokine levels, while preserving endothelial function. Additionally, it improved the aortic microbial profile, suggesting restoration of vascular homeostasis. CONCLUSION: mice. Regulating AhR/IDO could offer a potential therapeutic approach to mitigate systemic inflammation linked to periodontal infection. PLAIN LANGUAGE SUMMARY: Porphyromonas gingivalis (P. gingivalis), a major bacterial species of periodontal disease, promotes atherosclerosis (AS) by suppressing the protective AhR/IDO pathway-a key system that helps to control inflammation in blood vessels. Infection with P. gingivalis reduced the activity of IDO and AhR in the blood and aorta. When this pathway was activated using an AhR-stimulating compound, it significantly reduced AS plaque formation, inhibited inflammation, preserved blood vessel function, and improved the microbial balance in the aorta. These findings suggest that targeting the AhR/IDO pathway could be a promising strategy to reduce systemic inflammation and to slow the progression of atherosclerosis associated with periodontal disease, highlighting a potential link between oral health and cardiovascular health.