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香芹酚经口治疗可缓解携带人肠道微生物组的小鼠的急性弯曲杆菌病。

Therapeutic Oral Application of Carvacrol Alleviates Acute Campylobacteriosis in Mice Harboring a Human Gut Microbiota.

机构信息

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, 12203 Berlin, Germany.

出版信息

Biomolecules. 2023 Feb 8;13(2):320. doi: 10.3390/biom13020320.

Abstract

Human infections are rising globally. Since antibiotics are usually not indicated in acute campylobacteriosis, antibiotic-independent intervention measures are desirable. The phenolic compound carvacrol constitutes a promising candidate molecule given its antimicrobial and immune-modulatory features. To test the disease-alleviating effects of oral carvacrol treatment in acute murine campylobacteriosis, IL-10 mice harboring a human gut microbiota were perorally infected with and treated with carvacrol via the drinking water. Whereas stably established in the gastrointestinal tract of mice from the placebo cohort, carvacrol treatment resulted in lower pathogen loads in the small intestines on day 6 post infection. When compared to placebo, carvacrol ameliorated pathogen-induced symptoms including bloody diarrhea that was accompanied by less distinct histopathological and apoptotic cell responses in the colon. Furthermore, innate and adaptive immune cell numbers were lower in the colon of carvacrol- versus placebo-treated mice. Notably, carvacrol application dampened -induced secretion of pro-inflammatory mediators in intestinal, extra-intestinal and systemic organs to naive levels and furthermore, resulted in distinct shifts in the fecal microbiota composition. In conclusion, our preclinical placebo-controlled intervention study provides evidence that therapeutic carvacrol application constitutes a promising option to alleviate campylobacteriosis in the infected vertebrate host.

摘要

人类感染正在全球范围内上升。由于抗生素通常不适用于急性弯曲菌病,因此需要采取非抗生素干预措施。鉴于其抗菌和免疫调节特性,酚类化合物香芹酚是一种很有前途的候选分子。为了测试口服香芹酚治疗急性鼠弯曲菌病的疾病缓解效果,携带人类肠道微生物群的 IL-10 小鼠经口感染,并通过饮用水接受香芹酚治疗。虽然安慰剂组小鼠的胃肠道中稳定存在,但香芹酚治疗可导致感染后第 6 天小肠中的病原体负荷降低。与安慰剂相比,香芹酚改善了病原体引起的症状,包括血便,同时在结肠中观察到不那么明显的组织病理学和凋亡细胞反应。此外,香芹酚治疗组小鼠结肠中的固有和适应性免疫细胞数量较低。值得注意的是,香芹酚应用可抑制肠道、肠外和全身器官中 - 诱导的促炎介质的分泌,使其恢复到基础水平,并进一步导致粪便微生物群组成的明显变化。总之,我们的临床前安慰剂对照干预研究提供了证据,证明治疗性香芹酚应用是缓解感染脊椎动物宿主弯曲菌病的一种有前途的选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0e1/9953218/60bc09cf246d/biomolecules-13-00320-g001.jpg

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