Characterizing the intestinal chondroitin sulfate glycosaminoglycan sulfation signature in inflammatory bowel disease

Abstract

Abstract The intestinal extracellular matrix (ECM) helps maintain intestinal homeostasis, and pathologic ECM remodeling is implicated in inflammatory bowel disease (IBD). Chondroitin sulfate and dermatan sulfate glycosaminoglycans (CS/DS-GAGs) are integral components of the ECM, and alterations in CS/DS-GAGs significantly influence its function. However, it is unknown whether changes in CS/DS-GAG composition are linked to IBD. Our aim was to characterize the intestinal ECM CS/DS-GAG composition in active IBD using mass spectrometry to analyze intestinal biopsy samples. We characterized the intestinal CS/DS-GAG composition in 50 pediatric and young adult patients (n = 13 control, n = 37 IBD; age 7–23) and 6 adult patients (n = 6 control, age 24–67). The abundance of isomers associated with matrix stability (CS-A and DS) was significantly decreased in patients with IBD compared to controls, while isomers implicated in inflammation (CS-C and CS-E) were significantly increased. This imbalance of intestinal CS/DS isomers was restored among patients achieving clinical remission. Across the entire cohort, the abundance of pro-stabilizing CS/DS isomers negatively correlated with clinical disease activity scores, whereas both CS-C and CS-E content positively correlated with disease activity scores. Thus, pediatric patients with active IBD exhibited increased pro-inflammatory and decreased pro-stabilizing CS/DS isomer composition, and future studies are needed to determine whether changes in the CS/DS-GAG composition play a pathogenic role in IBD.