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Cited by 207Celiac Disease Research and ManagementEosinophilic EsophagitisInflammatory Bowel Disease

Fecal Gluten Peptides Reveal Limitations of Serological Tests and Food Questionnaires for Monitoring Gluten-Free Diet in Celiac Disease Patients

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Comino, Isabel, Fernández-Bañares, Fernando, Esteve, María, Ortigosa, Luís, Castillejo, Gemma, Fambuena, Blanca, Ribes-Koninckx, Carmen, Sierra, Carlos +32 more·2016·American Journal of Gastroenterology
DOI 10.1038/ajg.2016.439PMC PMC5059698
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Abstract

OBJECTIVES: Treatment for celiac disease (CD) is a lifelong strict gluten-free diet (GFD). Patients should be followed-up with dietary interviews and serology as CD markers to ensure adherence to the diet. However, none of these methods offer an accurate measure of dietary compliance. Our aim was to evaluate the measurement of gluten immunogenic peptides (GIP) in stools as a marker of GFD adherence in CD patients and compare it with traditional methods of GFD monitoring. METHODS: We performed a prospective, nonrandomized, multicenter study including 188 CD patients on GFD and 84 healthy controls. Subjects were given a dietary questionnaire and fecal GIP quantified by enzyme-linked immunosorbent assay (ELISA). Serological anti-tissue transglutaminase (anti-tTG) IgA and anti-deamidated gliadin peptide (anti-DGP) IgA antibodies were measured simultaneously. RESULTS: Of the 188 celiac patients, 56 (29.8%) had detectable GIP levels in stools. There was significant association between age and GIP in stools that revealed increasing dietary transgressions with advancing age (39.2% in subjects ≥13 years old) and with gender in certain age groups (60% in men ≥13 years old). No association was found between fecal GIP and dietary questionnaire or anti-tTG antibodies. However, association was detected between GIP and anti-DGP antibodies, although 46 of the 53 GIP stool-positive patients were negative for anti-DGP. CONCLUSIONS: Detection of gluten peptides in stools reveals limitations of traditional methods for monitoring GFD in celiac patients. The GIP ELISA enables direct and quantitative assessment of gluten exposure early after ingestion and could aid in the diagnosis and clinical management of nonresponsive CD and refractory CD. Trial registration number NCT02711397.

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  • Short dietary questionnaires and serum TGA determinations fail to detect dietary transgressions in children and adolescents with celiac disease, showing poor sensitivity to identify all patients who consume gluten.

    “Short dietary questionnaires and TGA determinations in serum fail to detect dietary transgressions in children and adolescents with CD, showing poor sensitivity to identify all patients who consume gluten (51-53).”

    From ESPGHAN Position Paper on Management and Follow-up of Children and Adolescents With Celiac Disease. (2022) · cites this paper as [53]

    The Results report that dietary questionnaires missed reported gluten consumption in 27 of 39 patients with detectable fecal gluten peptides, while serum anti-tTG was negative in 40 of 56 peptide-positive patients. These findings support poor detection, but they come from a cohort spanning ages 1–72; the paper does not establish the sensitivity of these methods specifically in children and adolescents. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • The analysis of faecal gluten immunogenic peptides (GIP) is the only objective non-invasive and valid biomarker to assess adherence to the gluten-free diet.

    “The only objective non-invasive and valid biomarker to assess adherence to the GFD is the analysis of faecal gluten immunogenic peptides (GIP), which has proven to detect recent intakes not identified by serology or dietary questionnaires (138,139).”

    From Gluten-free diet for pediatric patients with coeliac disease: A position paper from the ESPGHAN gastroenterology committee, special interest group in coeliac disease. (2024) · cites this paper as [138]

    The Discussion (page not provided) describes fecal GIP analysis as an accurate, noninvasive way to assess gluten exposure and reports that it detected more noncompliance than questionnaires or serology. It says the method *could become* the method of choice; it does not establish that it is the only valid objective noninvasive biomarker. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Faecal gluten immunogenic peptide analysis has proven to detect recent gluten intakes not identified by serology or dietary questionnaires.

    “which has proven to detect recent intakes not identified by serology or dietary questionnaires (138,139).”

    From Gluten-free diet for pediatric patients with coeliac disease: A position paper from the ESPGHAN gastroenterology committee, special interest group in coeliac disease. (2024) · cites this paper as [138]

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Authors
Comino, I., Fernández-Bañares, F., Esteve, M., Ortigosa, L., Castillejo, G., Fambuena, B., Ribes-Koninckx, C., Sierra, C., Rodríguez-Herrera, A., Salazar, J. C., Caunedo, Á., Marugán-Miguelsanz, J. M., Garrote, J. A., Vivas, S., lo Iacono, O., Nuñez, A., Vaquero, L., Vegas, A. M., Crespo, L., Fernández-Salazar, L., Arranz, E., Jiménez-García, V. A., Montes-Cano, M. A., Espín, B., Galera, A., Valverde, J., Girón, F. J., Bolonio, M., Millán, A., Cerezo, F. M., Guajardo, C., Alberto, J. R., Rosinach, M., Segura, V., León, F., Marinich, J., Muñoz-Suano, A., Romero-Gómez, M., Cebolla, Á., & Sousa, C.
Affiliations
  • Universidad de Sevilla (ES)
  • University Hospital Mútua de Terrassa (ES)
  • Hospital Universitario Nuestra Señora de Candelaria (ES)
  • Institut de Recerca Biomèdica Catalunya Sud (ES)
  • Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (ES)
  • Hospital Materno-Infantil (ES)
  • Hospital Universitario Virgen del Rocío (ES)
  • Hospital Universitario Virgen Macarena (ES)
  • Hospital Universitario Río Hortega (ES)
  • Hospital Universitario de León (ES)
  • Universidad de Valladolid (ES)
  • Instituto Hispalense de Pediatria (ES)
  • Hospital Universitari i Politècnic La Fe (ES)
  • Celimmune (United States) (US)
  • Biomedal (Spain) (ES)
Corresponding author
Sousa, Carolina
ORCID
Venue
American Journal of Gastroenterology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2016-10
Volume
111
Issue
10
Pages
1456-1465
ISSN
0002-9270 (ISSN-L)
DOI
10.1038/ajg.2016.439
PMC
PMC5059698
OpenAlex
W2523625783
Cited by
207
References
1
Citations by year
2026: 7 · 2025: 17 · 2024: 21 · 2023: 19 · 2022: 27 · 2021: 36 · 2020: 25 · 2019: 19 · 2018: 20 · 2017: 14 · 2016: 1
FWCI
19.71
Type
journal article
Language
en
Open access
Licence
Locations
  • The American Journal of Gastroenterology (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • UVaDOC UVaDOC University of Valladolid Documentary Repository (University of Valladolid) (publishedVersion, other-oa)
  • RISalud Institutional Health Repository of Andalucía (submittedVersion, cc-by-nc-nd)
  • Rovira & Virgili repository (submittedVersion, cc-by)
  • DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, cc-by-nc-nd)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by-nc-nd)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
  • Deposito de Investigacion Universidad de Sevilla (University of Seville) (submittedVersion, cc-by-nc-nd)
  • RISalud Institutional Health Repository of Andalucía (submittedVersion, other-oa)
Topics
  • Health Sciences › Medicine › Gastroenterology › Celiac Disease Research and Management
  • Health Sciences › Medicine › Surgery › Eosinophilic Esophagitis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
Keywords
celiac disease, gluten-free diet adherence, serological markers, anti-tissue transglutaminase antibodies, dietary questionnaire, refractory celiac disease
MeSH terms
Protein Glutamine gamma Glutamyltransferase 2, Adolescent, Age Factors, Antibodies, Autoantibodies, Celiac Disease, Child, Child, Preschool, Enzyme-Linked Immunosorbent Assay, Feces, Female, Gliadin, Glutens, Humans, Immunoglobulin A, Infant, Male, Patient Compliance, Prospective Studies, Transglutaminases, Surveys and Questionnaires, Serologic Tests, Diet Records, Case-Control Studies, GTP-Binding Proteins, Diet, Gluten-Free, Young Adult

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