Porphyromonas gingivalis (Pg) oral infection promotes atherosclerosis (AS) via suppression of the AhR/IDO pathway in ApoE-/- mice

Porphyromonas gingivalis (Pg) serves as a bridge connecting periodontology and atherosclerosis. Aryl Hydrocarbon Receptor (AhR) regulates the expression of the Indoleamine 2,3-dioxygenase (IDO) gene, which in turn regulates the Kynurenine (Kyn) metabolic pathway, thereby mitigating the progression of AS. Therefore, we aim to clarify whether AhR/IDO exerts a significant role in the atherosclerotic process facilitated by Pg. To create a model of periodontitis with atherosclerosis, we employed ApoE-/-mice that were given a high-fat diet and given an oral Pg inoculation for eight weeks. The cytokines associated with the AhR/IDO signaling pathway in aortic plaque were analyzed, and an AhR agonist was used to change the expression of the AhR/IDO pathway. Arteriosclerosis-related indicators and inflammatory factors were then measured and aortas were collected to analyze microbiome composition. Pg oral infection suppressed the level and activity of AhR/IDO signaling in the murine aorta. Activation of the AhR/IDO pathway also attenuated the lesion area and fibrosis from AS, alleviated inflammatory response, preserved endothelial function, and ameliorated the aortic microbial flora. Therefore, Pg may aggravate the development of AS by suppressing the AhR/IDO signaling pathway in ApoE-/- mice.