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黏液真杆菌可改善实验性结肠炎,且微生物代谢产物可通过增强黏膜完整性减轻结肠炎症反应。

Eubacterium limosum ameliorates experimental colitis and metabolite of microbe attenuates colonic inflammatory action with increase of mucosal integrity.

作者信息

Kanauchi Osamu, Fukuda Masanobu, Matsumoto Yoshiaki, Ishii Shino, Ozawa Toyokazu, Shimizu Makiko, Mitsuyama Keiichi, Andoh Akira

机构信息

Kirin Brewery Co. Ltd., 10-1-2 Shinkawa Chuo-ku, Tokyo 104-8288, Japan.

出版信息

World J Gastroenterol. 2006 Feb 21;12(7):1071-7. doi: 10.3748/wjg.v12.i7.1071.

Abstract

AIM

To examine the effect of Eubacterium limosum (E. limosum) on colonic epithelial cell line in vitro, and to evaluate the effect of E. limosum on experimental colitis.

METHODS

E. limosum was inoculated anaerobically and its metabolites were obtained. The growth stimulatory effect of the E. limosum metabolites on T84 cells was evaluated by SUDH activity, and the anti-inflammatory effect by IL-6 production. The change in mRNA of toll like receptor 4 (TLR4) was evaluated by real time PCR. Colitis was induced by feeding BALB/C mice with 2.0% dextran sodium sulfate. These mice received either 5% lyophilized E. limosum (n = 7) or control diet (n = 7). Seven days after colitis induction, clinical and histological scores, colon length, and cecal organic acid levels were determined.

RESULTS

The E. limosum produced butyrate, acetate, propionate, and lactate at 0.25, 1.0, 0.025 and 0.07 mmol/L, respectively in medium. At this concentration, each acid had no growth stimulating activity on T84 cells; however, when these acids were mixed together at the above levels, it showed significantly high activity than control. Except for lactate, these acids significantly attenuated IL-6 production at just 0.1 mmol/L. In addition, under TNF-alpha stimulation, butyrate attenuated the production of TLR4 mRNA. The treatment with E. limosum significantly attenuated clinical and histological scores of colitis with an increase of cecal butyrate levels, compared with the control group.

CONCLUSION

E. limosum can ameliorate experimental colonic inflammation. In part, the metabolite of E. limosum, butyrate, increases mucosal integrity and shows anti-inflammatory action modulation of mucosal defense system via TLR4.

摘要

目的

研究黏液真杆菌对体外结肠上皮细胞系的影响,并评估黏液真杆菌对实验性结肠炎的作用。

方法

对黏液真杆菌进行厌氧接种并获取其代谢产物。通过琥珀酸脱氢酶(SUDH)活性评估黏液真杆菌代谢产物对T84细胞的生长刺激作用,通过白细胞介素-6(IL-6)的产生评估其抗炎作用。采用实时聚合酶链反应(PCR)评估Toll样受体4(TLR4)的信使核糖核酸(mRNA)变化。通过给BALB/C小鼠喂食2.0%的葡聚糖硫酸钠诱导结肠炎。这些小鼠分别接受5%的冻干黏液真杆菌(n = 7)或对照饮食(n = 7)。在诱导结肠炎7天后,测定临床和组织学评分、结肠长度以及盲肠有机酸水平。

结果

黏液真杆菌在培养基中分别产生0.25、1.0、0.025和0.07 mmol/L的丁酸、乙酸、丙酸和乳酸。在此浓度下,每种酸对T84细胞均无生长刺激活性;然而,当这些酸以上述水平混合在一起时,其活性显著高于对照组。除乳酸外,这些酸在仅0.1 mmol/L时就能显著减弱IL-6的产生。此外,在肿瘤坏死因子-α(TNF-α)刺激下,丁酸可减弱TLR4 mRNA的产生。与对照组相比,黏液真杆菌治疗显著减轻了结肠炎的临床和组织学评分,同时盲肠丁酸水平升高。

结论

黏液真杆菌可改善实验性结肠炎症。黏液真杆菌的代谢产物丁酸部分地增加了黏膜完整性,并通过TLR4对黏膜防御系统发挥抗炎作用调节。

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