Apical Periodontitis Exacerbates Ulcerative Colitis Through NETs And Gut Dysbiosis

This study investigated the causal relationship between apical periodontitis (AP) and ulcerative colitis (UC) exacerbation, and elucidated the underlying mechanisms, focusing on neutrophil extracellular traps (NETs) and gut microbiota dysbiosis, a knowledge gap in oral-systemic inflammation research. Ethical approval was obtained. Thirty-two ICR mice underwent 8-week interventions: Control, AP (apical periodontitis), UC (ulcerative colitis), and AP+UC. Disease progression was assessed through clinical scoring and histopathology. Intestinal barrier integrity was quantified via tight junction protein immunofluorescence (ZO-1/Claudin1) and goblet cell staining. NETs were measured by ELISA and immunofluorescence co-localization. 16S rRNA sequencing analyzed gut microbial shifts. Statistical analyses employed ANOVA with Tukey's test. AP+UC mice exhibited significantly elevated disease activity (p<0.01) and exacerbated histopathological damage (p<0.05) compared to UC controls. Marked reductions in tight junction proteins (ZO-1/Claudin1) and goblet cell depletion (p<0.01) confirmed intestinal barrier impairment. Systemic NETs elevation (serum p<0.05; colon infiltration p<0.05) coincided with pathogenic microbiota dominance (Bacteroides/Escherichia, FDR<0.05). This study provides experimental evidence that: AP aggravates UC severity through oral-gut inflammatory crosstalk, and NETs formation and dysbiotic Bacteroides/Escherichia expansion may synergistically drive barrier dysfunction. The data provide compelling rationale for integrating oral health management into IBD therapeutic strategies.