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Background: The colonic mucus layer plays a critical role in intestinal homeostasis by limiting contact between luminal bacteria and the mucosal immune system. A defective mucus barrier in animal models allows bacterial contact with the intestinal epithelium and results in spontaneous colitis. A defective mucus barrier is also a key feature of active ulcerative colitis (UC). Alterations in the immune compartment due to intestinal bacterial breach in mice lacking the colon mucus barrier have not been characterized and correlated to active UC. Aims: To characterize alterations in the immune compartment due to intestinal bacterial breach in Muc2−/− mice, which lack the colon mucus barrier, and correlate the findings to active UC. Methods: Bacterial contact with colon epithelium and penetration into colon tissue was examined in Muc2−/− mice and colon biopsies from patients with active UC using fluorescence microscopy and qPCR. Neutrophils, lymphocytes, CD103+ dendritic cell subsets and macrophages in colon from Muc2−/− mice and biopsies from UC patients were quantitated by flow cytometry. Results: Inflamed UC patients and Muc2−/− mice had bacteria in contact with the colon epithelium. Bacterial rRNA was present in colonic mucosa in humans and Muc2−/− mice and in the draining lymph nodes of mice. Inflamed Muc2−/− mice and UC patients had elevated colon neutrophils, T cells and macrophages while a reduced frequency of CD103+ DCs was present in the inflamed colon of both mice and humans. Conclusions: The parallel features of the colon immune cell compartment in Muc2−/− mice and UC patients supports the usefulness of this model to understand the early phase of spontaneous colitis and will provide insight into novel strategies to treat UC. [ABSTRACT FROM AUTHOR]