Updated project metadata. A compromised pathology of the intestinal barrier have been associated with a series of inflammatory conditions where the routine controls nutrient absorption and pathogens exclusion is lost to different degrees. When the epithelial barrier is compromised, bacteria and their products can attack the cells and cause inflammation, sometime leading to sepsis. Studying the lymph peptidome in inflammatory bowel disease (IBD) can offer valuable insights into the underlying mechanisms, disease progression, and potential therapeutic targets. To assess the efficiency of gut immune barrier, we collected the pre-nodal lymph from Inflammatory Bowel Disease (IBD) subjects and performed a comprehensive peptidomic analysis. . The current study is complementary extension of the proteomics signature found in DSS-induced colitis mouse model, providing an insight in the lymph composition inclined to an inflammatory phenotype which was also mirrored by a unique set of peptidome/degradome. Furthermore, the identified peptides mapped to a wide range of intracellular and extracellular pathways, encompassing cellular stress, apoptosis, and extracellular matrix degradation related pathways. A significant fraction of peptides was also found to be derived from bacterial origin with a predicted binding affinity to different MHC I and MHC II human haplotypes.