Abstract
BACKGROUND: Periodontitis is a chronic inflammatory disease, having significant impact on systemic conditions. Ulcerative colitis (UC) is a chronic relapsing inflammatory disorder of the intestines. Studies have suggested a potential association between periodontitis and UC. This study aims to elucidate the influence of periodontitis on the progression of UC and to uncover the potential mechanistic pathways involved. METHODS: A total of 20 male C57BL/6J mice were randomly assigned to four groups: Sham, Periodontitis (P), UC, and Periodontitis + UC (P-UC). A chronic UC model was induced by alternating oral administration of 1% and 0.5% Dextran Sulfate Sodium Salt (DSS) solution, while periodontitis was induced by ligatures. Disease severity was accessed using Disease Activity Index (DAI), histopathology, and intestinal permeability assays. Gut microbiota and periodontal microbiota was analyzed using 16S rRNA sequencing. Tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) were measured by quantitative PCR (qPCR) to evaluate the systemic inflammation burden. Zonula occludens-1 (ZO-1) and occludin in intestinal tissues were assessed using qPCR and immunohistochemistry. Correlation analyses were performed between periodontal destruction indices and markers. RESULTS: A chronic UC model closely resembling clinical conditions was successfully established. The P-UC group exhibited earlier and more pronounced body weight loss than the UC group. Colonic inflammation was exacerbated, with significantly elevated TNF-α and IL-6 expression (P < 0.05). In the P-UC group, intestinal barrier disruption was evident with reduced occludin protein levels (P < 0.01) and increased intestinal permeability (P < 0.05), indicated by serum diamine oxidase (DAO). Both the P-UC and UC groups exhibited notable dysbiosis of the gut microbiota, with the P-UC group showing significantly higher abundance of UC-associated bacteria, such as Muribaculum and Allobaculum (P < 0.05), compared to the UC group. A trend toward reduced abundance of the gut-protective bacterium Akkermansia was also observed (P = 0.06). Pearson correlation analysis confirmed the association between periodontitis and intestinal inflammation, suggesting that intestinal barrier dysfunction and gut microbiota dysbiosis may be key mediators in periodontitis-induced UC exacerbation. CONCLUSION: Periodontitis may exacerbate UC by increasing harmful gut bacteria, reducing beneficial bacteria, and promoting the secretion of pro-inflammatory cytokines, thereby disrupting the intestinal barrier and worsening UC severity.