Proteus mirabilis exacerbate ulcerative colitis by inhibiting mucin production

Zhihui Jiang ¹ Pengpeng Li ¹ Kehui Qiu ¹ Yang Liao ¹ Xin Chen ¹ Ji Xuan ² Fangyu Wang ² Hongfeng Ma ^3* Ye Wang ^1* Minsheng Zhu ^1*

• ¹ State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing, China
• ² Department of General Surgery, Jinling Hospital, the Medical School of Nanjing University, Nanjing, China
• ³ Huzhou Rehabilitation Hospital, Huzhou, China

Ulcerative colitis (UC) is characterized by chronic inflammation and ulceration in colonic mucosa, accompanied by a defective epithelial barrier. Proteus mirabilis (P.mirabilis) bacterium is a putative intestinal pathogen with invasive ability, yet its role in UC inflammation and gut barrier disruption is unclear. This study aims to investigate its epidemiological presence, pathogenic roles and preventive strategy during UC inflammation. The fecal P.mirabilis bacteria were detected by PCR amplification of P.mirabilis-specific ureR gene. Of 41 UC patients, 65.9% patients were P.mirabilis positive, which was significantly higher than the controls. Administration of P.mirabilis aggravated dextran sulfate sodium-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 P.mirabilis could restore the mucus barrier and alleviate the enteric inflammation. Thus, our results suggest that P.mirabilis is a UC pathobiont bacterium, which exacerbate the severity of UC inflammation owing to down-regulation of mucin