DSS Colitis Model: Traps, Tricks, and Reporting Recommendations

The dextran sulfate sodium (DSS) colitis model is the most widely used experimental model of inflammatory bowel disease (IBD) due to its simplicity and versatility, with over 7,000 PubMed entries in the last decade and an exponential rise in recent years. Since its initial description in 1985, DSS colitis has been extensively evaluated across species, most notably in mice and rats, and has yielded substantial insights into IBD pathogenesis. However, the model’s multifactorial nature poses a dual challenge: it offers an opportunity but complicates study design, interpretation, and translational relevance. This complexity is worsened by inconsistent reporting, which hampers reproducibility and comparability across studies. The broad use of the DSS-induced colitis model yields numerous insights about the model, which help better understand its complexity, characteristics and limitations. Although DSS colitis is induced locally, inflammation in the colon and the gut barrier destruction may also affect other organs (such as the liver and brain) and their metabolism and molecular responses, which, in turn, influence colitis development, drug response, and the interpretation of results. These intrinsic (intra-experimental) characteristics of the DSS colitis are summarised in the paper (colitis, gut-brain axis, gut-liver axis). In addition, the DSS model is heavily influenced by numerous ex-trinsic (inter-experimental) factors (environmental, microbiological, genetic), which may further complicate the colitis model, the study outcomes, and data interpretation and are also discussed in the paper. As science advances and new data accumulate, understanding the intricate interplay among internal mechanisms, external factors, and technical variables becomes increasingly essential for accurate interpretation of DSS outcomes. This review synthesizes the complexity and interdependence of factors shaping the DSS model, emphasizing the need for meticulous reporting and consideration of methodological nuances to enhance reproducibility, interpretation, and translational value in DSS colitis research. In addition, the review provides practical guidance through a “traps & tricks” subsections and a checklist table designed to provide a framework and practical recommendations to better understand, apply, and interpret DSS model results in the context of broader systemic and methodological considerations.