Pancreatic glycoprotein 2 is a first line of defense for mucosal protection in intestinal inflammation.

Increases in adhesive and invasive commensal bacteria, such as Escherichia coli, and subsequent disruption of the epithelial barrier is implicated in the pathogenesis of inflammatory bowel disease (IBD). However, the protective systems against such barrier disruption are not fully understood. Here, we show that secretion of luminal glycoprotein 2 (GP2) from pancreatic acinar cells is induced in a TNF–dependent manner in mice with chemically induced colitis. Fecal GP2 concentration is also increased in Crohn's diease patients. Furthermore, pancreas-specific GP2-deficient colitis mice have more severe intestinal inflammation and a larger mucosal E. coli population than do intact mice, indicating that digestive-tract GP2 binds commensal E. coli, preventing epithelial attachment and penetration. Thus, the pancreas–intestinal barrier axis and pancreatic GP2 are important as a first line of defense against adhesive and invasive commensal bacteria during intestinal inflammation. Glycoprotein-2 (GP-2) can protect the intestinal epithelial barrier from bacteria and is associated with protection against Crohn's disease. Here, the authors show pancreatic GP-2 is the source of the intestine's luminal GP-2 that binds bacteria and prevents them from attaching to the epithelium, also limiting pathology in a DSS colitis mouse model. [ABSTRACT FROM AUTHOR]