title: The Role of Curcumin in Modulating Colonic Microbiota During Colitis and Colon Cancer Prevention.
abstract: 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.
authors.affiliation: *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.
authors.forename: Rita-Marie T
authors.initials: RM
authors.lastname: McFadden
authors.forename: Claire B
authors.initials: CB
authors.lastname: Larmonier
authors.forename: Kareem W
authors.initials: KW
authors.lastname: Shehab
authors.forename: Monica
authors.initials: M
authors.lastname: Midura-Kiela
authors.forename: Rajalakshmy
authors.initials: R
authors.lastname: Ramalingam
authors.forename: Christy A
authors.initials: CA
authors.lastname: Harrison
authors.forename: David G
authors.initials: DG
authors.lastname: Besselsen
authors.forename: John H
authors.initials: JH
authors.lastname: Chase
authors.forename: J Gregory
authors.initials: JG
authors.lastname: Caporaso
authors.forename: Christian
authors.initials: C
authors.lastname: Jobin
authors.forename: Fayez K
authors.initials: FK
authors.lastname: Ghishan
authors.forename: Pawel R
authors.initials: PR
authors.lastname: Kiela
mesh_terms: D000818:Animals; D001397:Azoxymethane / Q000008:administration & dosage; D002273:Carcinogens / Q000494:pharmacology; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy; D003106:Colon / Q000382:microbiology / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000139:chemically induced / Q000188:drug therapy*; D003474:Curcumin / Q000008:administration & dosage*; D019587:Dietary Supplements; D004195:Disease Models, Animal; D018928:Immunity, Mucosal; D007413:Intestinal Mucosa / Q000473:pathology*; D051379:Mice; D057507:Mice, 129 Strain; D018345:Mice, Knockout; D064307:Microbiota / Q000187:drug effects*
chemical_list: D002273:Carcinogens; D003474:Curcumin; D001397:Azoxymethane