Comparing urine and stool gluten immunogenic peptides for detecting compliance to gluten-free diets

Konstantinos Gkikas; Laura Gianolio; Miles Kavanagh; Bernadette White; Caroline Kerbiriou; Maria Lima; Vaios Svolos; Richard Hansen; Richard K Russell; Konstantinos Gerasimidis

doi:10.1038/s41390-025-04266-9

Comparing urine and stool gluten immunogenic peptides for detecting compliance to gluten-free diets

Pediatr Res. 2025 Jul 24. doi: 10.1038/s41390-025-04266-9. Online ahead of print.

Authors

Affiliations

¹ Human Nutrition, School of Medicine, University of Glasgow, New Lister Building, Glasgow Royal Infirmary, Glasgow, UK.
² Department of Paediatrics, Vittore Buzzi Children's Hospital, University of Milan, Milan, Italy.
³ Department of Nutrition & Dietetics, University of Thessaly, Trikala, Greece.
⁴ Department of Paediatric Gastroenterology, Hepatology and Nutrition, Royal Hospital for Children, Glasgow, UK.
⁵ Department of Child Health, Division of Respiratory Medicine and Gastroenterology, School of Medicine, University of Dundee, Dundee, UK.
⁶ Department of Paediatric Gastroenterology, Hepatology and Nutrition, Royal Hospital for Children and Young People, Edinburgh, UK.
⁷ Human Nutrition, School of Medicine, University of Glasgow, New Lister Building, Glasgow Royal Infirmary, Glasgow, UK. Konstantinos.gerasimidis@glasgow.ac.uk.

PMID: 40707834
DOI: 10.1038/s41390-025-04266-9

Abstract

Background: Detection of gluten immunogenic peptides (GIP) is a potential objective biomarker of adherence to gluten-free diet (GFD). As current methods require specialized laboratories, we evaluated novel point-of-care (POC) kits for GIP detection in stool and urine.

Methods: Ten children with Crohn's disease followed a 3-week GFD, after 8 weeks of exclusive enteral nutrition (EEN). 78 stool and urine samples were collected; one before EEN completion, six during the GFD, and one after return to unrestricted diet. Single samples were collected from 17 healthy adults after a 7-day EEN. Stool GIP was measured with reference ELISA (S-REF) and POC (S-POC) kits; urine GIP with POC kits (U-POC).

Results: Non-adherence to GFD was detected in 8/10 patients using S-REF, compared to 2/10 patients using conventional dietary assessment. Substantial inter-class agreement was noted between S-REF and S-POC (88% concordance, kappa = 0.74). Lower GIP levels, measured with S-REF, were seen in discordant compared to positive concordant samples. The optimal S-POC detection threshold was 0.11 mg/kg (sensitivity: 100%, specificity: 91%, p < 0.001). Agreement between S-REF and U-POC was lower (concordance: 73%, kappa = 0.39).

Conclusions: The S-POC kit is a suitable alternative for GIP detection, demonstrating high sensitivity and specificity except at very low GIP levels. Detection of GIP in urine is less accurate.

Impact: Detection of gluten immunogenic peptides (GIP) offers a promising objective biomarker for monitoring adherence to gluten-free diets. However, current methods require specialized labs and long processing times. By measuring GIP in stool, we identified children with Crohn's disease who were non-adherent despite standard assessments indicating otherwise. A point-of-care GIP kit demonstrated high sensitivity and specificity in detecting GIP in stool making it a potential alternative to the reference ELISA method. In contrast, GIP detection using urine kits was suboptimal. Our study supports the potential clinical utility of bedside point-of-care GIP kits that may improve treatment adherence and efficacy of gluten-free-diets.