Fusobacterium nucleatumexacerbates colitis by damaging epithelial barriers and inducing aberrant inflammation

Objective Fusobacterium nucleatum(F. nucleatum) has been reported to be enriched in patients with inflammatory bowel disease (IBD). This study aimed to explore the role ofF. nucleatumin IBD and its pathogenic mechanism. Methods Several bacteria that have been reported to be associated with IBD or colorectal cancer were measured in the fecal samples of 91 patients with IBD and 43 healthy individuals. Mice with dextran sulfate sodium (DSS)-induced colitis and a Caco-2 cell line were used to explore the pathogenicity ofF. nucleatum. Barrier damage was evaluated by a transmission electron microscope, the permeability of fluorescein isothiocyanate-dextran, transepithelial electrical resistance and immunofluorescence. Protein levels of the cell-cell junction and activation of the STAT3 signaling pathway were detected by immunohistochemistry and immunoblot. Cytokine secretion and T-cell differentiation were measured by quantitative real-time polymerase chain reaction and flow cytometry. Results F. nucleatumwas significantly enriched in the feces of patients with IBD and its abundance correlated with disease activity. Administration ofF. nucleatummarkedly exacerbated colitis in a DSS mouse model. Mechanistically,F. nucleatumdamaged epithelial integrity and increased permeability by regulating the expression and distribution of tight junction proteins zonula occludens-1 and occludin. Moreover,F. nucleatumpromoted the secretion of cytokines (tumor necrosis factor-alpha, interferon-gamma, interleukin [IL]-1 beta, IL-6, and IL-17), activated the STAT3 signaling pathway, and induced CD4(+)T cell proliferation and Th1 and Th17 subset differentiations. Conclusion F. nucleatumcan damage the intestinal barrier and induce aberrant inflammation, which exacerbates colitis.