The PIONIR Trial - Gut Jan. 2026

The PIONIR (Preventing IBD ONset in Individuals at Risk) trial, as described in the study published in Gut, January 2026, focuses on evaluating whether the Tasty&Healthy diet can reduce the risk of developing Crohn’s disease (CD) in first-degree relatives (FDRs) of CD patients. This trial is significant because FDRs are at a higher genetic and environmental risk of developing CD. The study also addresses the challenge of identifying the optimal preclinical stage of CD for enrolling participants in prevention trials.

In the pre-PIONIR screening stage, faecal calprotectin, a biomarker of intestinal inflammation, was measured in asymptomatic FDRs aged 6–38 years. Of the 950 individuals approached, 331 (35%) participated in the screening. Persistent elevation of calprotectin (>70 µg/g in at least two tests) was observed in 63 individuals (19% of those screened). Further diagnostic evaluations (via panenteric video capsule-endoscopy or ileocolonoscopy) revealed that 9 individuals (2.7%) had endoscopic findings consistent with presymptomatic CD. Another 33 individuals (17.9% of those screened) were categorized as having "potential pre-CD" based on non-specific mucosal changes or histological inflammation.

The study demonstrated that calprotectin levels >225 µg/g were highly predictive of presymptomatic CD, with an area under the receiver operating characteristic curve of 0.97, sensitivity of 89%, and specificity of 94%. Additionally, the findings underscored the variability in single calprotectin measurements, with 22% of cases normalizing upon repeat testing.

In conclusion, the PIONIR trial highlights the utility of faecal calprotectin as a tool for identifying at-risk individuals and emphasizes the importance of early detection in designing preventive strategies for CD. The findings pave the way for future prevention trials targeting high-risk populations.