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Apical Periodontitis May Exacerbate Ulcerative Colitis via Neutrophil Extracellular Trap‐Mediated Systemic Inflammation and Intestinal Barrier Disruption in Mice

Year: 2026

Type: article

Abstract: AIM: This study investigated the impact of apical periodontitis (AP) on ulcerative colitis (UC) progression and elucidated the roles of intestinal barrier dysfunction and neutrophil extracellular traps (NETs) in a mouse model, providing new evidence and perspectives for oral-systemic diseases. METHODOLOGY: Thirty-two male ICR mice were randomized into four groups (n = 8 per group): Ctrl, AP, UC and AP + UC. AP was induced by lipopolysaccharide application to the bilateral maxillary first and second molars. UC was established via dextran sulphate sodium administration. Disease activity index (DAI), colon length and histopathology were assessed. Serum levels of C-reactive protein (CRP), interleukin (IL)-6, IL-10, IL-1β, immunoglobulin G (IgG) and NETs were measured by ELISA. Intestinal tight junction proteins (ZO-1 and Claudin) and NETs were analysed via immunofluorescence. Gut microbiota composition was evaluated by 16S rRNA sequencing. RESULTS: AP + UC mice exhibited significantly higher DAI scores (p < 0.01 vs. UC), shortened colon length (p < 0.05 vs. UC) and exacerbated histopathological damage (p < 0.01 vs. UC). Serum CRP, IL-1β and IL-6 levels were elevated in AP + UC mice (p < 0.05 vs. UC). Levels of NETs increased significantly in AP + UC serum (p < 0.05 vs. UC) and colonic tissue. AP and AP + UC groups showed reduced goblet cell areas (p < 0.01 AP vs. Ctrl, p < 0.01 AP + UC vs. UC) and diminished tight junction protein expression. Gut microbiota analysis revealed increased alpha diversity and altered genus-level composition in AP + UC mice, with significant correlations between specific bacteria and NETs levels/goblet cell areas. CONCLUSION: AP may exacerbate UC severity through intestinal barrier impairment and systemic NETs elevation, accompanied by gut microbiota dysbiosis.

Source: International Endodontic Journal

DOI: 10.1111/iej.70182