Background <p>Enhanced expression of mucosal addressin cell adhesion molecule 1 (MAdCAM-1) on high endothelial venules facilitates lymphocyte migration to sites of intestinal inflammation in inflammatory bowel disease (IBD). This process may be accompanied by increased shedding of soluble MAdCAM-1 (sMAdCAM-1) from endothelial cells. Hence, circulating sMAdCAM-1 may serve as a biomarker of intestinal inflammation in IBD.</p> Results <p>This single-center study enrolled pediatric (<i>n</i> = 32) and adult (<i>n</i> = 73) patients with IBD, as well as healthy controls (<i>n</i> = 56). Serum samples were collected from all participants, and sMAdCAM-1 concentrations were quantified using an ELISA assay. In healthy individuals, sMAdCAM-1 levels were highest in early childhood, declined during adolescence, and were lowest in adulthood. Concentrations of sMAdCAM-1 did not correlate with gut inflammation in pediatric or adult patients with Crohn’s disease (CD). In contrast, significantly increased sMAdCAM-1 levels were observed in adults with severe ulcerative colitis (UC). Moreover, sMAdCAM-1 levels distinguished healthy children from pediatric UC patients.</p> Conclusions <p>These findings provide new insights into sMAdCAM-1 as a marker of gut homeostasis and inflammation. Shedding of sMAdCAM-1 decreases during adolescence, and circulating sMAdCAM-1 levels could serve as a biomarker for ulcerative colitis in both pediatric and adult patients, particularly in severe disease.</p>