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