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

McFadden RT1, Larmonier CB, Shehab KW, Midura-Kiela M, Ramalingam R, Harrison CA, Besselsen DG, Chase JH, Caporaso JG, Jobin C, Ghishan FK, Kiela PR. Inflamm Bowel Dis. 2015 Jul 25. [Epub ahead of print]
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1*Department of Pediatrics, Steele Children's Research Center, University of Arizona Health Sciences Center, Tucson, Arizona; †School of Dentistry, Oral Biology Program, University of North Carolina, Chapel Hill, North Carolina; ‡University Animal Care, University of Arizona Health Sciences Center, Tucson, Arizona; §Department of Biological Sciences, Center for Microbial Genetics and Genomics at Northern Arizona University, Flagstaff, Arizona; ‖Department of Medicine, Division of Gastroenterology, College of Medicine, University of Florida, Gainesville, Florida; and ¶Department of Immunobiology, University of Arizona Health Sciences Center, Tucson, Arizona.


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-buffred 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.

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