The Interconnection Between Periodontitis and Inflammatory Bowel Disease

Abstract

Abstract Objective Periodontitis, an oral infection affecting ~50% of Americans, is associated with the pathogenesis of inflammatory bowel disease (IBD), however, the contributory mechanisms remain ill defined. Previous GWAS studies have identified SNPs in the Interferon Regulatory Factor 8 (IRF8) gene as risk factors for IBD. The objective of this study was to explore the relationship between periodontitis and IBD using Irf8 knockout (KO) mice. Methods Periodontitis was induced in wild-type (WT) and Irf8 KO mice using the well-established oral ligature-induced periodontitis (LIP) model. The effects of LIP on oral bacterial colonization in the mouth and gut were measured by 16S rRNA and shotgun metagenomics sequencing. The influence of LIP on oral bacteria-mediated immune cell infiltration in the colonic mucosa was measured by flow cytometry, RT-qPCR, and ELISA. Results LIP promoted expansion of native oral pathogens and accumulation of the same species in the mouth and gut of Irf8 KO mice, which was associated with colitis development in Irf8 KO mice when compared to WT mice. LIP Irf8 KO mice exhibited ~2-fold increased infiltration of Th17 cells and ~2–4-fold decrease infiltration of Th1 and Treg cells in the colonic mucosa, which led to over production of IL17 and decreased production of IFN-γ and IL10. Similarly, IL-1β-producing cells were found to be higher in the colonic mucosa of LIP Irf8 KO vs WT mice. Resolution of periodontitis correlated with reduced intestinal load of oral bacteria and reversal of colitis in Irf8 KO mice. Conclusion Our study provides new perspectives on the pathophysiology of IBD. Irf8 deficiency along with dysbiotic oral and gut microbiota promote colitis in mice by activating IL17 and IL-1β signaling pathways.