Basic Research
Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Feb 21, 2006; 12(7): 1071-1077
Published online Feb 21, 2006. doi: 10.3748/wjg.v12.i7.1071
Eubacterium limosum ameliorates experimental colitis and metabolite of microbe attenuates colonic inflammatory action with increase of mucosal integrity
Osamu Kanauchi, Masanobu Fukuda, Yoshiaki Matsumoto, Shino Ishii, Toyokazu Ozawa, Makiko Shimizu, Keiichi Mitsuyama, Akira Andoh
Osamu Kanauchi, Masanobu Fukuda, Kirin Brewery Co. Ltd., 10-1-2 Shinkawa Chuo-ku, Tokyo, 104-8288, Japan
Yoshiaki Matsumoto, College of Pharmacy, Nihon University; 7-7-1 Narashinodai, Funabashi, Chiba 274-8555, Japan
Shino Ishii, Toyokazu Ozawa, Makiko Shimizu, Department of Clinical Pharmacology and Toxicology, Showa Pharmaceutical University, 3-3165, Higashi- Tamagawagakuen, Machida, Tokyo, 194-8543, Japan
Keiichi Mitsuyama, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan
Akira Andoh, Shiga University of Medical Science, Tsukinowa, Seta, Otsu, Shiga, 520-2100, Japan
Correspondence to: Osamu Kanauchi, Kirin Brewery Co. Ltd., 10-1-2 Shinkawa Chuo-ku, Tokyo 104-8288, Japan.
Telephone: +81-3-5541-5873 Fax: +81-3-5541-5874
Received: March 10, 2005
Revised: July 2, 2005
Accepted: August 26, 2005
Published online: February 21, 2006

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-α 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.

Keywords: Intestinal Microflora, Butyrate, Eubacterium limosum, Toll like receptor, IL-6