In the DSS-induced colitis model, the epithelial damage and resulting inflammation is restricted to the colon, with a potential influence on the microbial composition in the adjacent cecum. Several studies have reported changes of the gut microbiota in the DSS-induced colitis model and other mouse models of IBD. Furthermore, metaproteomics analysis of the gut microbiome in a mouse model of Crohn’s disease demonstrated that disease severity and location are microbiota-dependent, with clear evidence for the causal role of bacterial dysbiosis in the development of chronic ileal inflammation. We have developed a refined model of chronic DSS-induced colitis that reflects typical symptoms of human IBD without a risky body weight loss usually observed in DSS models [Hoffmann et al., submitted]. In this study, we used metaproteomics to characterize the disease-related changes in bacterial protein abundance and function in the refined model of DSS-induced colitis. To assess the structural and functional changes, we applied 16S rRNA gene sequencing and metaproteomics analysis of the intestinal microbiota in three different entities of the intestinal environment, i.e. colon mucus, colon content and cecum content.