Reduced fecal GP2 levels in ulcerative colitis associate with inflammatory activity and microbial composition

Loss of tolerance to GP2, an antimicrobial immune-modulating component of intestinal cells and receptor on microfold cells, is associated with disease severity in Crohn's disease (CD). However, the role of GP2 in inflammatory bowel diseases remains poorly understood. This study aimed to evaluate fecal GP2 levels in patients with ulcerative colitis (UC) and CD and to examine associations with disease activity, response to biologic therapy, and microbial features.

We conducted a retrospective study of adults with UC, CD, and healthy controls recruited at a tertiary IBD clinic. Fecal GP2 levels and serum anti-GP2 antibodies were measured using ELISA and correlated with disease activity, inflammatory biomarkers (CRP, fecal calprotectin and elastase activity), and microbiome assessed by 16S rRNA amplicon sequencing.

The study included 87 patients with CD, 58 with UC, and 31 healthy controls. Fecal GP2 levels were significantly lower in UC, particularly in active UC, compared with CD or controls (P ≤ 0.05). In CD, fecal GP2 levels did not differ significantly from controls across activity strata but correlated with elastase activity. Further, fecal GP2 levels increased following induction therapy among clinical responders and were associated with gut microbial diversity. No correlation was observed between serum anti-GP2 and fecal GP2 levels, or serum anti-GP2 and responsiveness to induction therapy.

Fecal GP2 concentrations are reduced in UC, particularly during active disease, but are preserved in CD. This suggests a disease-specific pattern in UC, potentially reflecting altered microbial interactions or increased luminal protein degradation.