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阿克曼氏菌黏液亚种 ATCC BAA-835 菌株不会促进无菌性白细胞介素-10 缺陷型小鼠的短期肠道炎症。

Akkermansia muciniphila strain ATCC BAA-835 does not promote short-term intestinal inflammation in gnotobiotic interleukin-10-deficient mice.

机构信息

a Department Gastrointestinal Microbiology , German Institute of Human Nutrition Potsdam-Rehbruecke , Nuthetal , Germany.

b Institute of Veterinary Pathology , Freie Universitaet Berlin , Berlin , Germany.

出版信息

Gut Microbes. 2019;10(2):188-203. doi: 10.1080/19490976.2018.1511663. Epub 2018 Sep 25.

Abstract

Akkermansia muciniphila is a common member of the intestinal microbiota of healthy human individuals. Its abundance is negatively associated with inflammatory bowel disease and metabolic disorders and the oral administration of A. muciniphila improves the symptoms of metabolic disease in mice. Therefore, A. muciniphila is a promising candidate for the treatment of type-2 diabetes and obesity. However, some studies using animal models of intestinal inflammation reported that A. muciniphila may exacerbate gut inflammation. Because of these contradictory reports the present study aimed to clarify the role of A. muciniphila in the development of intestinal inflammation and the conditions promoting it. For this purpose, the short-term colitogenic potential of A. muciniphila strain ATCC BAA-835 was investigated in colitis-prone, gnotobiotic IL-10-deficient (Il10) mice. Il10 mice mono-associated with A. muciniphila showed no signs of intestinal inflammation based on body-weight change, histopathological scoring and inflammatory markers. Additional association of the mice with the colitogenic Escherichia coli strain NC101 led to cecal but not colonic inflammation. However, the severity of the inflammation did not exceed that observed in mice mono-associated with E. coli NC101. Il10 mice colonized with a simplified human intestinal microbiota showed increased histopathology, but no increase in inflammatory markers. Furthermore, co-colonization with A. muciniphila did not modify histopathology. The turnover of intestinal mucus was similar in all groups despite the mucus-degrading property of A. muciniphila. Overall, the data do not support a short-term pro-inflammatory effect of A. muciniphila strain ATCC BAA-835 in the Il10 mouse model for inflammatory bowel disease.

摘要

黏蛋白阿克曼氏菌是健康人体肠道微生物群的常见成员。其丰度与炎症性肠病和代谢紊乱呈负相关,口服黏蛋白阿克曼氏菌可改善代谢疾病小鼠的症状。因此,黏蛋白阿克曼氏菌是治疗 2 型糖尿病和肥胖症的有希望的候选物。然而,一些使用肠道炎症动物模型的研究报告称,黏蛋白阿克曼氏菌可能会加重肠道炎症。由于这些相互矛盾的报告,本研究旨在阐明黏蛋白阿克曼氏菌在肠道炎症发展中的作用及其促进条件。为此,研究了黏蛋白阿克曼氏菌菌株 ATCC BAA-835 在易患结肠炎的无菌 IL-10 缺陷(Il10)小鼠中的短期结肠炎潜力。根据体重变化、组织病理学评分和炎症标志物,与黏蛋白阿克曼氏菌单定植的 Il10 小鼠没有出现肠道炎症迹象。将小鼠与结肠炎大肠杆菌菌株 NC101 进一步关联导致盲肠而不是结肠炎症。然而,炎症的严重程度没有超过与 NC101 大肠杆菌单定植的小鼠。定植有简化的人类肠道微生物群的 Il10 小鼠显示出组织病理学增加,但炎症标志物没有增加。此外,与黏蛋白阿克曼氏菌共同定植不会改变组织病理学。尽管黏蛋白阿克曼氏菌具有降解黏液的特性,但所有组的肠道黏液周转率相似。总体而言,数据不支持黏蛋白阿克曼氏菌菌株 ATCC BAA-835 在炎症性肠病 Il10 小鼠模型中具有短期促炎作用。

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