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结肠炎小鼠的肠道类固醇谱和微生物群落组成。

Intestinal steroid profiles and microbiota composition in colitic mice.

机构信息

German Institute of Human Nutrition Potsdam-Rehbruecke Department of Gastrointestinal Microbiology Arthur-Scheunert-Allee 114-116 14558 Nuthetal, Germany.

出版信息

Gut Microbes. 2011 May-Jun;2(3):159-66. doi: 10.4161/gmic.2.3.16104.

Abstract

Reduced gut microbiota diversity in conjunction with a bloom of few bacterial species is a common feature in inflammatory bowel disease (IBD) patients. However, the environmental changes caused by inflammation and their possible impact on the microbiota are largely unknown. Since IBD is associated with an impaired intestinal steroid metabolism, we hypothesized that changes in intestinal steroid and particularly bile acid (BA) concentrations affect microbial communities. We used Interleukin-10 deficient (IL-10-/-) mice as a model for chronic gut inflammation. Healthy wild-type mice served as controls. In these animals, intestinal steroid concentrations and gut microbial diversity were analyzed at 24 weeks of age. The IL 10-/- mice developed moderate inflammation in cecum and colon and colorectal tumor formation was observed in 55 % of the animals. Compared to the healthy conditions, gut inflammation was associated with higher intestinal cholesterol and cholic acid concentrations and a reduced microbial diversity. The latter was accompanied by a proliferation of Robinsoniella peoriensis, Clostridium innocuum, Escherichia coli, and Enterococcus gallinarum. All these species proved to be highly bile acid resistant. We concluded that chronic colitis in IL-10-/- mice is associated with changes in intestinal steroid profiles. These changes may be due to alterations in gut microbiota composition or vice versa. Whether the bacterial sterol and bile acid metabolism is implicated in colitis and colorectal carcinoma etiology remains to be clarified.

摘要

肠道微生物多样性降低,同时少数细菌物种大量繁殖,这是炎症性肠病(IBD)患者的常见特征。然而,炎症引起的环境变化及其对微生物群可能产生的影响在很大程度上仍不清楚。由于 IBD 与肠道类固醇代谢受损有关,我们假设肠道类固醇,特别是胆汁酸(BA)浓度的变化会影响微生物群落。我们使用白细胞介素-10 缺陷(IL-10-/-)小鼠作为慢性肠道炎症模型。健康的野生型小鼠作为对照。在这些动物中,我们在 24 周龄时分析了肠道类固醇浓度和肠道微生物多样性。IL-10-/-小鼠在盲肠和结肠中发生中度炎症,并且 55%的动物出现结直肠肿瘤形成。与健康状态相比,肠道炎症与更高的肠道胆固醇和胆酸浓度以及微生物多样性降低有关。后者伴随着罗比氏菌(Robinsoniella peoriensis)、无害梭菌(Clostridium innocuum)、大肠杆菌(Escherichia coli)和鸡肠球菌(Enterococcus gallinarum)的大量增殖。所有这些物种都被证明具有很强的耐胆酸能力。我们得出结论,IL-10-/-小鼠的慢性结肠炎与肠道类固醇谱的变化有关。这些变化可能是由于肠道微生物群组成的改变或反之亦然。细菌固醇和胆汁酸代谢是否参与结肠炎和结直肠癌的发病机制仍有待阐明。

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