S1940 Age-Dependent Variability in Acute Colitis: Bridging Preclinical Models and Human Disease Insights

Introduction: Acute colitis (AC) in children is a significant global health concern due to severe inflammatory phenotypes that are often resistant to standard therapies. Preclinical models to study AC frequently overlook age-related differences in immune responses. In the present study, we investigated the physiological, histological, and transcriptomic differences between juvenile and adult Sprague-Dawley (SD) rats with dextran sulfate sodium (DSS) induced AC. Methods: Experiments were conducted on juvenile (3-4 weeks old) and adult (6-7 weeks old) SD rats, following the Administrative Panel on Laboratory Animal Care approval at Stanford University. AC was induced by administering 5.5% DSS in the animal’s drinking water over 6 days. Daily assessments included body weight, stool consistency (scored from Normal (0) to Diarrhea (2)) and presence of blood via a Hemoccult test (scored from Negative (0) to Gross bleeding (3)). A total of 96 rats were analyzed. Post-sacrifice, tissue samples from the ileum, proximal and distal colon were collected for histological analysis in which they were fixed in 10% neutral-buffered formalin and stained with hematoxylin and eosin. For transcriptome analysis, distal colon samples were preserved in RNA later at −80°C and bulk RNA sequencing was performed with differential gene expression analysis conducted with a corrected P-value threshold of 0.05 and an absolute fold change of ±1. Results: Juvenile rats exhibited a more severe presentation of DSS-induced AC compared to adult animals, evidenced by stool consistency, blood presence, and acute inflammation. Females showed greater severity than males in both age groups. Transcriptomic analysis indicated that juvenile animals exhibited a robust neutrophil-mediated inflammatory response, while adults displayed a lymphocytic immune response characterized by elevated tumor necrosis factor expression. Conclusion: These findings highlight age-dependent variability in acute colitis, emphasizing the need for tailored therapeutic strategies and the translational relevance of findings in juvenile animals for pediatric patients.