Jiang Zhihui, Li Pengpeng, Qiu Kehui, Liao Yang, Chen Xin, Xuan Ji, Wang Fangyu, Ma Hongfeng, Wang Ye, Zhu Minsheng
State Key Laboratory of Pharmaceutical Biotechnology, Suqian Scientific Research Institute of Nanjing University Medical School, Gulou Hospital of the Medical School, Nanjing University, Nanjing, China.
Department of Gastroenterology, Jinling Hospital, The Medical School of Nanjing University, Nanjing, China.
Front Microbiol. 2025 Mar 25;16:1556953. doi: 10.3389/fmicb.2025.1556953. eCollection 2025.
Ulcerative colitis (UC) is characterized by chronic inflammation and ulceration in colonic mucosa, accompanied by a defective epithelial barrier. () 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.
culture and PCR amplification of the -specific gene were used to detect fecal P. mirabilis and determine its prevalence in UC and control stool specimens. 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 in colitis animals.
The fecal bacteria were detected by PCR amplification of -specific gene. Of 41 UC patients, 65.9% patients were positive, which was significantly higher than the controls. Administration of 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 could restore the mucus barrier and alleviate the enteric inflammation. Thus, our results suggest that 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 may be effective in limiting UC inflammation.
溃疡性结肠炎（UC）的特征是结肠黏膜的慢性炎症和溃疡形成，同时伴有上皮屏障功能缺陷。奇异变形杆菌是一种具有侵袭能力的潜在肠道病原体，但其在UC炎症和肠道屏障破坏中的作用尚不清楚。本研究旨在调查其在UC炎症期间的流行病学存在情况、致病作用和预防策略。
采用奇异变形杆菌特异性基因的培养和PCR扩增来检测粪便中的奇异变形杆菌，并确定其在UC和对照粪便标本中的患病率。将从UC粪便标本中分离出的奇异变形杆菌灌胃给硫酸葡聚糖钠（DSS）处理的小鼠。通过组织学检查和细胞因子定量评估结肠的炎症和黏液层。筛选噬菌体并用于消除结肠炎动物体内的奇异变形杆菌。
通过奇异变形杆菌特异性基因的PCR扩增检测到粪便中的奇异变形杆菌。在41例UC患者中，65.9%的患者奇异变形杆菌呈阳性，显著高于对照组。给小鼠施用奇异变形杆菌会加重DSS诱导的结肠炎症状和黏膜炎症。有趣的是，动物的结肠黏液层（上皮屏障的重要组成部分）被显著破坏，这与人类UC结肠的改变一致。黏液层的破坏是由肠道上皮中IL-18的下调介导的。重要的是，一种靶向奇异变形杆菌的噬菌体混合物可以恢复黏液屏障并减轻肠道炎症。因此，我们的结果表明奇异变形杆菌是一种UC致病共生菌，由于黏蛋白产生和IL-18表达的下调而加剧了UC炎症的严重程度。噬菌体介导的奇异变形杆菌清除可能对限制UC炎症有效。
