Related Experiment Video
Updated: May 10, 2026
Non-invasive Assessment of the Efficacy of New Therapeutics for Intestinal Pathologies Using Serial Endoscopic Imaging of Live Mice
Published on: March 10, 2015
Proteus mirabilis exacerbates ulcerative colitis by inhibiting mucin production
Zhihui Jiang1, Pengpeng Li1, Kehui Qiu1
1State Key Laboratory of Pharmaceutical Biotechnology, Suqian Scientific Research Institute of Nanjing University Medical School, Gulou Hospital of the Medical School, Nanjing University, Nanjing, China.
Introduction:
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.
Method:
P. mirabilis culture and PCR amplification of the P. mirabilis-specific ureR gene were used to detect fecal P. mirabilis and determine its prevalence in UC and control stool specimens. P. mirabilis isolated from UC stool specimens was gavaged into dextran sulfate sodium (DSS)-treated mice. Inflammation and the mucus layer of colons were assessed through histological examination and cytokine quantification. Bacteriophages were screened and used to eliminate P. mirabilis in colitis animals.
Results And Discussion:
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 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 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 exacerbates the severity of UC inflammation owing to down-regulation of mucin production and IL-18 expression. Bacteriophage-mediated elimination of P. mirabilis may be effective in limiting UC inflammation.
Insights
Proteus mirabilis exacerbates ulcerative colitis (UC) by disrupting the gut barrier and down-regulating IL-18. Bacteriophages effectively eliminate this bacterium, offering a potential therapeutic strategy for UC patients.
Area of Science:
- Gastroenterology
- Microbiology
- Immunology
Background:
- Ulcerative colitis (UC) involves chronic colonic inflammation and a compromised epithelial barrier.
- The role of Proteus mirabilis (P. mirabilis) in UC pathogenesis, particularly its impact on gut barrier integrity, remains largely unexplored.
Purpose of the Study:
- To investigate the prevalence of P. mirabilis in UC patients.
- To elucidate the pathogenic mechanisms of P. mirabilis in exacerbating UC inflammation and disrupting the gut barrier.
- To evaluate bacteriophage therapy as a preventive strategy against P. mirabilis-induced UC.
Main Methods:
- Fecal P. mirabilis detection using PCR for the ureR gene.
- Induction of colitis in mice using dextran sulfate sodium (DSS) and P. mirabilis gavage.
- Histological and cytokine analysis of colonic tissues.
- Screening and application of bacteriophages targeting P. mirabilis.
Main Results:
- P. mirabilis was detected in 65.9% of UC patients, significantly higher than controls.
- P. mirabilis aggravated DSS-induced colitis, causing significant mucosal inflammation and disruption of the colonic mucus layer.
- Mucus layer disruption was linked to down-regulated IL-18 expression in the intestinal epithelium.
- A bacteriophage cocktail successfully restored the mucus barrier and reduced inflammation.
Conclusions:
- P. mirabilis acts as a pathobiont in UC, worsening inflammation by reducing mucin production and IL-18 expression.
- Bacteriophage therapy presents a promising approach for eliminating P. mirabilis and mitigating UC severity.
Related Concept Videos
01:24Pathophysiology of Peptic Ulcer Disease: Mucosal Defense Factors
01:20Drugs for Peptic Ulcer Disease: Prostaglandin Analogs as Mucosal Protective Agents
Non-steroidal anti-inflammatory drugs (NSAIDs) can induce peptic ulcers by inhibiting cyclooxygenase, decreasing...
01:29Drugs for Treatment of Ulcerative Colitis in IBD
01:28Peptic Ulcer Disease II: Pathophysiology
Damaging agents such as Helicobacter pylori, gastric acid, pepsin, and nonsteroidal anti-inflammatory drugs (NSAIDs) can weaken the mucosal defense, allowing hydrogen ions to infiltrate back and harm epithelial cells.
01:24Peptic Ulcer Disease II: Pathophysiology
01:20Inflammatory Bowel Disease II: Ulcerative Colitis