The effect of creatine supplementation on AOM/DSS induced colitis associated colorectal cancer in C57BL/6 mice

Colitis-associated colorectal cancer (CAC) is a serious complication of inflammatory bowel disease (IBD) with complex etiology involving chronic inflammation, immune dysregulation, and gut microbiota dysbiosis. Creatine, a natural nitrogenous com-pound, possesses anti-inflammatory and immunomodulatory properties, but its role in CAC remains unclear.We established an AOM/DSS-induced mouse model of CAC and supplemented mice with creatine. We assessed the effects of creatine on colitis severity, tumor burden, and histopathology. Additionally, we investigated the impact of crea-tine on gut barrier function, macrophage polarization, and gut microbiota composi-tion.Creatine supplementation significantly alleviated DSS-induced colitis, reduced tumor burden, and delayed CAC progression in mice. Mechanistically, creatine im-proved gut barrier function by protecting tight junction proteins from degradation in-duced by the modeling stimulus，influenced macrophage polarization, and main-tained gut microbiota diversity, promoting the abundance of beneficial bacteria while reducing harmful ones.Our findings suggest that creatine supplementation may rep-resent a promising supportive therapy for IBD and CAC by modulating the gut micro-biota and immune microenvironment. Further investigation is warranted to explore the clinical potential of creatine in the management of CAC. The CAC model was established by intraperitoneal injection of AOM at a dose of 10 mg/kg body weight while the control group received an equivalent volume of normal saline via intraperitoneal injection. One week later, the animals were given drinking water containing 2.5% DSS for 7 days, followed by nor-mal drinking water for 14 days. This cycle was repeated three times.