PDF(Pubmed)
Abstract：
UNASSIGNED: Human infections with the food-borne enteropathogen Campylobacter jejuni are responsible for increasing incidences of acute campylobacteriosis cases worldwide. Since antibiotic treatment is usually not indicated and the severity of the enteritis directly correlates with the risk of developing serious autoimmune disease later-on, novel antibiotics-independent intervention strategies with non-toxic compounds to ameliorate and even prevent campylobacteriosis are utmost wanted. Given its known pleiotropic health-promoting properties, curcumin constitutes such a promising candidate molecule. In our actual preclinical placebo-controlled intervention trial, we tested the anti-microbial and anti-inflammatory effects of oral curcumin pretreatment during acute experimental campylobacteriosis.
UNASSIGNED: Therefore, secondary abiotic IL-10-/- mice were challenged with synthetic curcumin via the drinking water starting a week prior oral C. jejuni infection. To assess anti-pathogenic, clinical, immune-modulatory, and functional effects of curcumin prophylaxis, gastrointestinal C. jejuni bacteria were cultured, clinical signs and colonic histopathological changes quantitated, pro-inflammatory immune cell responses determined by in situ immunohistochemistry and intestinal, extra-intestinal and systemic pro-inflammatory mediator measurements, and finally, intestinal epithelial barrier function tested by electrophysiological resistance analysis of colonic ex vivo biopsies in the Ussing chamber.
UNASSIGNED: Whereas placebo counterparts were suffering from severe enterocolitis characterized by wasting symptoms and bloody diarrhea on day 6 post-infection, curcumin pretreated mice, however, were clinically far less compromised and displayed less severe microscopic inflammatory sequelae such as histopathological changes and epithelial cell apoptosis in the colon. In addition, curcumin pretreatment could mitigate pro-inflammatory innate and adaptive immune responses in the intestinal tract and importantly, rescue colonic epithelial barrier integrity upon C. jejuni infection. Remarkably, the disease-mitigating effects of exogenous curcumin was also observed in organs beyond the infected intestines and strikingly, even systemically given basal hepatic, renal, and serum concentrations of pro-inflammatory mediators measured in curcumin pretreated mice on day 6 post-infection. In conclusion, the anti-Campylobacter and disease-mitigating including anti-inflammatory effects upon oral curcumin application observed here highlight the polyphenolic compound as a promising antibiotics-independent option for the prevention from severe acute campylobacteriosis and its potential post-infectious complications.
UNASSIGNED: Therefore, secondary abiotic IL-10-/- mice were challenged with synthetic curcumin via the drinking water starting a week prior oral C. jejuni infection. To assess anti-pathogenic, clinical, immune-modulatory, and functional effects of curcumin prophylaxis, gastrointestinal C. jejuni bacteria were cultured, clinical signs and colonic histopathological changes quantitated, pro-inflammatory immune cell responses determined by in situ immunohistochemistry and intestinal, extra-intestinal and systemic pro-inflammatory mediator measurements, and finally, intestinal epithelial barrier function tested by electrophysiological resistance analysis of colonic ex vivo biopsies in the Ussing chamber.
UNASSIGNED: Whereas placebo counterparts were suffering from severe enterocolitis characterized by wasting symptoms and bloody diarrhea on day 6 post-infection, curcumin pretreated mice, however, were clinically far less compromised and displayed less severe microscopic inflammatory sequelae such as histopathological changes and epithelial cell apoptosis in the colon. In addition, curcumin pretreatment could mitigate pro-inflammatory innate and adaptive immune responses in the intestinal tract and importantly, rescue colonic epithelial barrier integrity upon C. jejuni infection. Remarkably, the disease-mitigating effects of exogenous curcumin was also observed in organs beyond the infected intestines and strikingly, even systemically given basal hepatic, renal, and serum concentrations of pro-inflammatory mediators measured in curcumin pretreated mice on day 6 post-infection. In conclusion, the anti-Campylobacter and disease-mitigating including anti-inflammatory effects upon oral curcumin application observed here highlight the polyphenolic compound as a promising antibiotics-independent option for the prevention from severe acute campylobacteriosis and its potential post-infectious complications.
摘要：
■人类感染食源性肠病原体空肠弯曲杆菌是全球急性弯曲杆菌病发病率增加的原因。由于通常不需要抗生素治疗，并且肠炎的严重程度与以后发生严重自身免疫性疾病的风险直接相关，最需要使用无毒化合物改善甚至预防弯曲杆菌病的新型不依赖抗生素的干预策略。鉴于其已知的多效性健康促进特性，姜黄素构成了这种有希望的候选分子。在我们实际的临床前安慰剂对照干预试验中，我们测试了急性实验性弯曲杆菌病期间口服姜黄素预处理的抗微生物和抗炎作用。
■因此，在口服空肠杆菌感染前一周开始,通过饮用水用合成姜黄素攻击继发性非生物IL-10-/-小鼠。为了评估抗致病性，临床,免疫调节，和姜黄素预防的功能作用，胃肠道空肠杆菌培养，临床体征和结肠组织病理学变化定量，通过原位免疫组织化学和肠，肠外和全身促炎介质测量，最后，通过对Ussing室中的结肠离体活检的电生理电阻分析来测试肠上皮屏障功能。
安慰剂组患者在感染后第6天出现严重小肠结肠炎，表现为消瘦症状和血性腹泻，姜黄素预处理的小鼠，然而,在临床上受到的损害要小得多，并且显示出不那么严重的微观炎症后遗症，例如结肠的组织病理学变化和上皮细胞凋亡。此外,姜黄素预处理可以减轻肠道中的促炎先天性和适应性免疫反应，重要的是，在空肠杆菌感染后挽救结肠上皮屏障的完整性。值得注意的是,在感染的肠道以外的器官中也观察到外源性姜黄素的疾病缓解作用，甚至全身给予基底肝，肾,和在感染后第6天在姜黄素预处理的小鼠中测量的促炎介质的血清浓度。总之,此处观察到的姜黄素口服应用时的抗弯曲杆菌和疾病缓解作用,包括抗炎作用,突出表明多酚化合物是预防严重急性弯曲杆菌病及其潜在感染后并发症的有希望的不依赖抗生素的选择.
■因此，在口服空肠杆菌感染前一周开始,通过饮用水用合成姜黄素攻击继发性非生物IL-10-/-小鼠。为了评估抗致病性，临床,免疫调节，和姜黄素预防的功能作用，胃肠道空肠杆菌培养，临床体征和结肠组织病理学变化定量，通过原位免疫组织化学和肠，肠外和全身促炎介质测量，最后，通过对Ussing室中的结肠离体活检的电生理电阻分析来测试肠上皮屏障功能。
安慰剂组患者在感染后第6天出现严重小肠结肠炎，表现为消瘦症状和血性腹泻，姜黄素预处理的小鼠，然而,在临床上受到的损害要小得多，并且显示出不那么严重的微观炎症后遗症，例如结肠的组织病理学变化和上皮细胞凋亡。此外,姜黄素预处理可以减轻肠道中的促炎先天性和适应性免疫反应，重要的是，在空肠杆菌感染后挽救结肠上皮屏障的完整性。值得注意的是,在感染的肠道以外的器官中也观察到外源性姜黄素的疾病缓解作用，甚至全身给予基底肝，肾,和在感染后第6天在姜黄素预处理的小鼠中测量的促炎介质的血清浓度。总之,此处观察到的姜黄素口服应用时的抗弯曲杆菌和疾病缓解作用,包括抗炎作用,突出表明多酚化合物是预防严重急性弯曲杆菌病及其潜在感染后并发症的有希望的不依赖抗生素的选择.
