Proteus mirabilis exacerbates ulcerative colitis by inhibiting mucin production

The fecal <i>P. mirabilis</i> bacteria were detected by PCR amplification of <i>P. mirabilis</i>-specific <i>ureR</i> gene. Of 41 UC patients, 65.9% patients were <i>P. mirabilis</i> positive, which was significantly higher than the controls. Administration of <i>P. mirabilis</i> aggravated DSS-induced colitis symptom and mucosal inflammation in mice. Interestingly, the colonic mucus layer, an essential component of the epithelial barrier, of the animals was dramatically disrupted, which was consistent with the alteration of human UC colon. The disrupted mucus layer was mediated by the down-regulation of IL-18 in intestinal epithelium. Importantly, a bacteriophage cocktail targeting <i>P. mirabilis</i> could restore the mucus barrier and alleviate the enteric inflammation. Thus, our results suggest that <i>P. mirabilis</i> is a UC pathobiont bacterium, which exacerbates the severity of UC inflammation owing to down-regulation of mucin production and IL-18 expression. Bacteriophage-mediated elimination of <i>P. mirabilis</i> may be effective in limiting UC inflammation.