Porphyromonas Gingivalis Exacerbates Atherosclerosis By Inhibiting The Ahr/Ido Pathway

To investigate the role of the AhR/IDO (Aryl Hydrocarbon Receptor/Indoleamine 2,3-Dioxygenase) pathway, a key regulator of kynurenine (Kyn) metabolism, in modulating AS progression facilitated by periodontitis with Porphyromonas gingivalis (P. gingivalis)-induced. Male ApoE-/- mice (8 weeks old) fed a high-fat diet were orally inoculated with P. gingivalis (strain ATCC 33277) for 8 weeks to establish a periodontitis-AS comorbidity model. The AhR agonist 6-formylindolo[3,2-b]carbazole (FICZ) was administered intraperitoneally to pharmacologically activate the AhR/IDO pathway in animal models. Atherosclerotic plaque formation was assessed via Oil Red O, Masson’s trichrome, and hematoxylin-eosin (HE) staining. Immunohistochemistry (IHC), RT-qPCR, and enzyme linked immunosorbent assay (ELISA) were employed to evaluate AhR/IDO-related cytokines, markers of endothelial dysfunction, and inflammatory factors. 16S rRNA sequencing was conducted to evaluate microbiome dysbiosis in aortic tissues. P. gingivalis infection significantly suppressed AhR/IDO signaling in aortic tissue and serum of ApoE-/- mice. Conversely, FICZ-induced AhR/IDO activation attenuated plaque formation, reduced fibrous cap thinning, mitigated systemic inflammation, improved endothelial integrity, and restored microbial homeostasis in ApoE-/- infected with P. gingivalis-infection. P. gingivalis may exacerbate AS by inhibiting the AhR/IDO signaling pathway in ApoE-/- mice, suggesting that targeting the AhR/IDO axis may represent a novel therapeutic strategy for periodontitis-associated AS.