Localized Rectal Dextran Sulfate Sodium-Induced Colitis Is Associated with Small-Intestinal Shortening and Gut-Liver...

Ulcerative colitis (UC) is a chronic inflammatory bowel disease marked by inflammation of the colon. Although various dextran sulfate sodium (DSS)-induced UC models are available, the traditional free-drinking model involves oral administration, which complicates the assessment of extracolonic organs because of widespread intestinal exposure. This study aimed to create a localized UC model through rectal administration of DSS and evaluate whether this approach minimized direct DSS exposure to the small intestine and liver. Rats received 40% DSS rectally for 13 d. Changes in body weight, Disease Activity Index, and histological scores were monitored. The effects of 5-aminosalicylic acid treatment were examined, and small intestinal morphology, inflammatory markers, bile flow, and mRNA levels of hepatic bile salt export pump were analyzed. Rectal DSS induced localized inflammation in the distal colon and rectum, mimicking key features of UC such as weight loss, mucosal injury, and elevated disease activity. Some of these effects were partially alleviated by 5-aminosalicylic acid treatment. The small intestine shortened without infiltration of inflammatory cells or cytokine increase, indicating a non-inflammatory structural change. Bile flow and hepatic bile salt export pump expression significantly decreased in DSS-treated rats, suggesting hepatobiliary excretory dysfunction. Overall, the rectal DSS model offers a controlled and reproducible way to induce colon-specific inflammation, overcoming the limitations of the free-drinking model, which hinders extracolonic evaluation due to oral DSS exposure. This model may provide a research basis for further study of inter-organ interactions, particularly gut-liver axis dysfunction and intestinal barrier-related drug absorption in UC.