Mousavi Soraya, Busmann Lia V, Bandick Rasmus, Shayya Nizar W, Bereswill Stefan, Heimesaat Markus M
Gastrointestinal Microbiology Research Group, Institute of Microbiology, Infectious Diseases and Immunology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Eur J Microbiol Immunol (Bp). 2023 Nov 21;13(3):88-105. doi: 10.1556/1886.2023.00037. Print 2023 Nov 23.
Acute campylobacteriosis caused by oral infections with the enteropathogen Campylobacter jejuni represent serious threats to global human health. Since novel treatment options with safe and antibiotics-independent compounds would be highly appreciable, we here investigated the anti-bacterial and disease-alleviating effects of carvacrol, butyrate, ellagic acid, and 2'-fucosyl-lactose in acute murine campylobacteriosis. To address this, secondary abiotic IL-10-/- mice were perorally infected with C. jejuni and treated with either compound alone or all four in combination via the drinking water starting two days post-infection.
On day 6, the duodenal pathogen loads were lower in mice of the combination versus the vehicle treatment cohort. Importantly, mice treated with carvacrol and the combination presented with less distinct diarrheal symptoms, colonic histopathology, epithelial cell apoptosis, and immune cell responses when compared to vehicle counterparts on day 6 post-infection. Furthermore, the combination treatment did not only diminish colonic IFN-γ, TNF-α, and IL-6 secretion in C. jejuni infected mice, but also dampened extra-intestinal and even systemic pro-inflammatory cytokine concentrations to basal levels as measured in liver, kidneys, lungs, and serum samples.
Our preclinical placebo-controlled intervention trial provides evidence that the combined oral application of carvacrol, butyrate, ellagic acid, and 2'-fucosyl-lactose alleviates acute campylobacteriosis in the vertebrate host.
由肠道病原体空肠弯曲菌经口感染引起的急性弯曲菌病对全球人类健康构成严重威胁。由于具有安全且不依赖抗生素的新型治疗方案将非常受欢迎，我们在此研究了香芹酚、丁酸盐、鞣花酸和2'-岩藻糖基乳糖在急性小鼠弯曲菌病中的抗菌和缓解疾病作用。为了解决这个问题，对二级无特定病原体的IL-10基因敲除小鼠经口感染空肠弯曲菌，并在感染后两天开始通过饮用水单独给予任一化合物或四种化合物联合给药进行治疗。
在第6天，联合治疗组小鼠十二指肠中的病原体载量低于载体治疗组。重要的是，与感染后第6天的载体对照组相比，用香芹酚和联合治疗的小鼠腹泻症状、结肠组织病理学、上皮细胞凋亡和免疫细胞反应不那么明显。此外，联合治疗不仅减少了空肠弯曲菌感染小鼠结肠中IFN-γ、TNF-α和IL-6的分泌，还将肝、肾、肺和血清样本中测量的肠外甚至全身促炎细胞因子浓度降低到基础水平。
我们的临床前安慰剂对照干预试验提供了证据，表明联合口服香芹酚、丁酸盐、鞣花酸和2'-岩藻糖基乳糖可减轻脊椎动物宿主的急性弯曲菌病。
