The prevalence of human infections with the zoonotic pathogen Campylobacter jejuni is rising worldwide. Therefore, the identification of compounds with potent anti-pathogenic and anti-inflammatory properties for future therapeutic and/or preventive application to combat campylobacteriosis is of importance for global health. Results of recent studies suggested carvacrol (4-isopropyl-2-methylphenol) as potential candidate molecule for the treatment of campylobacteriosis in humans and for the prevention of Campylobacter colonization in farm animals. To address this in a clinical murine infection model of acute campylobacteriosis, secondary abiotic IL-10−/− mice were subjected to synthetic carvacrol via the drinking water starting 4 days before peroral C. jejuni challenge. Whereas at day 6 post-infection placebo treated mice suffered from acute enterocolitis, mice from the carvacrol cohort not only harbored two log orders of magnitude lower pathogen loads in their intestines, but also displayed significantly reduced disease symptoms. Alleviated campylobacteriosis following carvacrol application was accompanied by less distinct intestinal apoptosis and pro-inflammatory immune responses as well as by higher numbers of proliferating colonic epithelial cells. Remarkably, the inflammation-ameliorating effects of carvacrol treatment were not restricted to the intestinal tract, but could also be observed in extra-intestinal organs such as liver, kidneys and lungs and, strikingly, systemically as indicated by lower IFN-γ, TNF, MCP-1 and IL-6 serum concentrations in carvacrol versus placebo treated mice. Furthermore, carvacrol treatment was associated with less frequent translocation of viable C. jejuni originating from the intestines to extra-intestinal compartments. The lowered C. jejuni loads and alleviated symptoms observed in the here applied clinical murine model for human campylobacteriosis highlight the application of carvacrol as a promising novel option for both, the treatment of campylobacteriosis and hence, for prevention of post-infectious sequelae in humans, and for the reduction of C. jejuni colonization in the intestines of vertebrate lifestock animals.

中文翻译：

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香芹酚可改善临床小鼠感染模型中的急性弯曲菌病


全球人类感染人畜共患病原体空肠弯曲菌的患病率正在上升。因此，鉴定具有有效抗病原体和抗炎特性的化合物，用于未来对抗弯曲菌病的治疗和/或预防应用对于全球健康具有重要意义。最近的研究结果表明香芹酚（4-异丙基-2-甲基苯酚）是治疗人类弯曲杆菌病和预防农场动物弯曲杆菌定植的潜在候选分子。为了在急性弯曲菌病的临床鼠感染模型中解决这个问题，在口服空肠弯曲菌攻击前4天开始，继发性非生物IL-10−/−小鼠通过饮用水接受合成香芹酚。在感染后第 6 天，安慰剂治疗的小鼠患有急性小肠结肠炎，而香芹酚组的小鼠不仅其肠道内的病原体负荷降低了两个对数级，而且还表现出显着减轻的疾病症状。应用香芹酚后弯曲菌病得到缓解，同时伴有不太明显的肠道细胞凋亡和促炎性免疫反应以及更多数量的结肠上皮细胞增殖。值得注意的是，香芹酚治疗的炎症改善作用不仅限于肠道，还可以在肠外器官（如肝、肾和肺）中观察到，并且引人注目的是，如 IFN-γ、TNF、香芹酚与安慰剂治疗小鼠的 MCP-1 和 IL-6 血清浓度。此外，香芹酚治疗与源自肠道的活空肠弯曲菌向肠外区室的转移频率较低有关。降低的C. 在此应用的人类弯曲菌病临床鼠模型中观察到的空肠负荷和减轻的症状突出表明，香芹酚作为一种有前景的新选择，用于治疗弯曲菌病，从而预防人类感染后后遗症，并减少感染后遗症的发生。空肠弯曲杆菌在脊椎动物家畜肠道中的定殖。