The Role of Curcumin in Modulating Colonic Microbiota During Colitis and Colon Cancer Prevention

被引:195
作者
McFadden, Rita-Marie T. [1 ,2 ]
Larmonier, Claire B. [1 ]
Shehab, Kareem W. [1 ]
Midura-Kiela, Monica [1 ]
Ramalingam, Rajalakshmy [1 ]
Harrison, Christy A. [1 ]
Besselsen, David G. [3 ]
Chase, John H. [4 ]
Caporaso, J. Gregory [4 ]
Jobin, Christian [5 ]
Ghishan, Fayez K. [1 ]
Kiela, Pawel R. [1 ,6 ]
机构
[1] Univ Arizona, Hlth Sci Ctr, Steele Childrens Res Ctr, Dept Pediat, Tucson, AZ 85724 USA
[2] Univ N Carolina, Sch Dent, Oral Biol Program, Chapel Hill, NC USA
[3] Univ Arizona, Hlth Sci Ctr, Univ Anim Care, Tucson, AZ 85724 USA
[4] No Arizona Univ, Dept Biol Sci, Ctr Microbial Genet & Genom, Flagstaff, AZ 86011 USA
[5] Univ Florida, Coll Med, Dept Med, Div Gastroenterol, Gainesville, FL USA
[6] Univ Arizona, Hlth Sci Ctr, Dept Immunobiol, Tucson, AZ 85724 USA
关键词
INFLAMMATORY-BOWEL-DISEASE; I CLINICAL-TRIAL; DIETARY CURCUMIN; COLORECTAL-CANCER; INTESTINAL INFLAMMATION; GUT MICROBIOTA; MOUSE MODEL; RISK-FACTOR; CARCINOGENESIS; NEOPLASIA;
D O I
10.1097/MIB.0000000000000522
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background: Intestinal microbiota influences the progression of colitis-associated colorectal cancer. With diet being a key determinant of the gut microbial ecology, dietary interventions are an attractive avenue for the prevention of colitis-associated colorectal cancer. Curcumin is the most active constituent of the ground rhizome of the Curcuma longa plant, which has been demonstrated to have anti-inflammatory, antioxidative, and antiproliferative properties. Methods: Il10 -/- mice on 129/SvEv background were used as a model of colitis-associated colorectal cancer. Starting at 10 weeks of age, wild-type or Il10 -/- mice received 6 weekly intraperitoneal injections of azoxymethane (AOM) or phosphate-buffered saline (PBS) and were started on either a control or a curcumin-supplemented diet. Stools were collected every 4 weeks for microbial community analysis. Mice were killed at 30 weeks of age. Results: Curcumin-supplemented diet increased survival, decreased colon weight/length ratio, and, at 0.5%, entirely eliminated tumor burden. Although colonic histology indicated improvement with curcumin, no effects of mucosal immune responses have been observed in PBS/Il10 -/- mice and limited effects were seen in AOM/Il10 -/- mice. In wild-type and in Il10 -/- mice, curcumin increased bacterial richness, prevented age-related decrease in alpha diversity, increased the relative abundance of Lactobacillales, and decreased Coriobacterales order. Taxonomic profile of AOM/Il10 -/- mice receiving curcumin was more similar to those of wild-type mice than those fed control diet. Conclusions: In AOM/Il10 -/- model, curcumin reduced or eliminated colonic tumor burden with limited effects on mucosal immune responses. The beneficial effect of curcumin on tumorigenesis was associated with the maintenance of a more diverse colonic microbial ecology. © 2015 Crohn's & Colitis Foundation of America, Inc.
引用
收藏
页码:2483 / 2494
页数:12
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