Department of Internal Medicine, Tainan Hospital, Ministry of Health and Welfare Department of Internal Medicine Graduate Institute of Clinical Medicine, National Health Research Institutes, Tainan, Taiwan.
Department of Internal Medicine Center for Infection Control, National Cheng Kung University Hospital Department of Medicine, National Cheng Kung University Medical College.
J Infect Dis. 2015 Aug 15;212(4):654-63. doi: 10.1093/infdis/jiv184. Epub 2015 Mar 24.
Clostridium difficile is currently the leading cause of infectious diarrhea in hospitalized patients. In addition to the infection due to toxigenic C. difficile in the gastrointestinal tract of susceptible hosts, other predisposing factors for C. difficile infection (CDI) are identified, including advanced age, a prolonged hospital stay, and use of acid-suppressive drugs. Of note, exposure to gastric acid-reducing agents, such as H2 blockers and proton pump inhibitors (PPIs), remains a controversial risk factor, and has been associated with CDI in some studies but not in others. A mouse model of antibiotic-associated clostridial colitis was established to examine the role of PPIs for CDI.
A mouse model of antibiotic-associated clostridial colitis was set up. NF-κB reporter mice were used to address the in vivo spatial and temporal inflammatory patterns of C. difficile-associated colitis. Serum levels of lipopolysaccharide and dextran-FITC were measured to reflect the barrier permeability of affected intestines.
Mice with CDI that were exposed to PPI exhibited greater losses of stool consistency and body and cecal weights than those that were not exposed to PPI. Further, more neutrophilic infiltrations, epithelial damage, and inflammatory cytokine expression were noted in colon specimens of the mice with PPI exposure. More-evident inflammatory responses were detected by in vivo imaging of NF-κB reporter mice with CDI that were exposed to PPI. Gut barrier permeability was increased to a greater extent, as reflected by higher serum levels of lipopolysaccharide and dextran-FITC in mice with CDI that were exposed to PPI.
Our mouse model demonstrates that PPI exposure increases the severity of intestinal inflammation in mice with C. difficile-associated colitis.
艰难梭菌是目前住院患者感染性腹泻的主要原因。除了在易感宿主的胃肠道中因产毒艰难梭菌感染外，还确定了其他导致艰难梭菌感染（CDI）的诱发因素，包括高龄、住院时间延长和使用抑酸药物。值得注意的是，暴露于胃酸减少剂，如 H2 阻滞剂和质子泵抑制剂（PPIs），仍然是一个有争议的危险因素，在一些研究中与 CDI 相关，但在其他研究中则没有。建立了一种抗生素相关性艰难梭菌结肠炎的小鼠模型，以研究 PPI 对 CDI 的作用。
建立了一种抗生素相关性艰难梭菌结肠炎的小鼠模型。使用 NF-κB 报告小鼠来解决与艰难梭菌相关结肠炎相关的体内时空炎症模式。测量血清中脂多糖和葡聚糖-FITC 的水平，以反映受影响肠道的屏障通透性。
暴露于 PPI 的 CDI 小鼠表现出更大的粪便稠度、体重和盲肠重量损失，而未暴露于 PPI 的小鼠则没有。此外，在暴露于 PPI 的小鼠的结肠标本中，观察到更多的嗜中性粒细胞浸润、上皮损伤和炎症细胞因子表达。通过对暴露于 PPI 的 CDI 小鼠的 NF-κB 报告小鼠进行体内成像，检测到更明显的炎症反应。暴露于 PPI 的 CDI 小鼠的肠道屏障通透性增加更明显，反映在血清中脂多糖和葡聚糖-FITC 水平升高。
我们的小鼠模型表明，PPI 暴露增加了艰难梭菌相关性结肠炎小鼠肠道炎症的严重程度。
