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

Background: Inflammatory bowel diseases (IBD) are a major risk factor for colon cancer. Intestinal microbiota have been identified as the target of inflammation that affects the progression of colitis-associated colorectal cancer (CAC). With diet being a key determinant of the gut microbial ecology, dietary interventions are an attractive avenue for the prevention of CAC. Curcumin is the most active constituent of the ground rhizome of the Curcuma Longa plant, which has been demonstrated to have anti-inflammatory, anti-oxidative, pro-apoptotic and anti-proliferative properties. However, the exact role of curcumin in colon cancer prevention and modulation of the microbial communities are yet to be determined. Methods: A mouse model of CAC was utilized in which Il10-/- mice on 129/SvEv background develop progressive colitis. On the starting day, WT or Il10-/- mice received a 100µL i.p. injection of 10mg/kg body weight of azoxymethane (AOM) or sterile saline (continued once a week for six weeks total) and were started on one of the following curcumin-supplemented diets: 0%, 0.05%, 0.1% or 0.5%. Mice were monitored for weight loss, rectal prolapse, rectal bleeding, and stool consistency. Stools were collected every four weeks for microbial analysis (Illumina 16S rRNA profiling). At the conclusion of the study, mice were assessed for tumor burden, colonic histopathology and colonic cytokine profile. Results: Curcumin-supplemented diets increased survival, decreased colon weight/length ratios and reduced tumor burden in a dose-dependent manner. Distal colon histopathology in Il10-/- mice exposed to AOM with the 0.5% curcumin diet demonstrated a reduction of inflammation score and a reduction in the frequency of adenocarcinoma detection. Curcumin altered the microbial ecology in the gut of Il10-/- mice fed the 0.5% curcumin diet. DIfferences in microbial diversity were observed in mice with tumors vs. without, as well as in mice that had spontaneous vs. AOM-induced tumors. Conclusions: In a dose-dependent manner, dietary curcumin results in a less severe presentation of colitis, in a reduced risk of progression to CRC upon exposure to AOM and a more diverse colonic microbial ecology in the Il10-/- mice. This suggests that curcumin functions as an effective agent for restoring healthy gut homeostasis.Doctor of Philosoph