Serum zonulin and its diagnostic performance in non-coeliac gluten sensitivity

Maria Raffaella Barbaro, Cesare Cremon, Antonio Maria Morselli-Labate, Antonio Di Sabatino, Paolo Giuffrida, Gino Roberto Corazza, Michele Di Stefano, Giacomo Caio, Giovanni Latella, Carolina Ciacci, Daniele Fuschi, Marianna Mastroroberto, Lara Bellacosa, Vincenzo Stanghellini, Umberto Volta, Giovanni Barbara

Research output: Contribution to journalArticle

Abstract

Objective: Non-coeliac gluten sensitivity (NCGS) is characterised by intestinal and extraintestinal symptoms related to the ingestion of gluten-containing foods, in the absence of coeliac disease (CD) and wheat allergy. No biomarkers are available to diagnose NCGS and the gold standard double-blind placebo-controlled gluten challenge is clinically impractical. The aim of our work was to investigate the role of serum zonulin as a diagnostic biomarker of NCGS and to develop a diagnostic algorithm. Design: In a multicentre study, we enrolled 86 patients with either self-reported or double-blind confirmed NCGS, 59 patients with diarrhoea-predominant IBS (IBS-D), 15 patients with CD and 25 asymptomatic controls (AC). Zonulin serum levels were assessed and the associated diagnostic power calculated. Clinical and symptomatic data were recorded. The effect of diet on zonulin levels was evaluated in a subgroup of patients with NCGS. Results: Compared with ACs, the NCGS, irrespective of modality of diagnosis, and patients with CD had significantly increased levels of zonulin, as did both NCGS and patients with CD compared with participants with IBS-D. Self-reported NCGS showed increased zonulin levels compared with double-blind confirmed and not-confirmed NCGS. Six-month wheat avoidance significantly reduced zonulin levels only in HLA-DQ2/8-positive participants with NCGS. The diagnostic accuracy of zonulin levels in distinguishing NCGS from IBS-D was 81%. After exclusion of CD, a diagnostic algorithm combining zonulin levels, symptoms and gender improved the accuracy to 89%. Conclusion: Zonulin can be considered a diagnostic biomarker in NCGS and combined with demographic and clinical data differentiates NCGS from IBS-D with high accuracy. Wheat withdrawal was associated with a reduction in zonulin levels only in NCGS carrying HLA genotype.

Original languageEnglish
JournalGut
DOIs
Publication statusAccepted/In press - Jan 1 2020

    Fingerprint

Keywords

  • epithelial barrier
  • functional bowel disorder
  • irritable bowel syndrome
  • nutrition

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Barbaro, M. R., Cremon, C., Morselli-Labate, A. M., Di Sabatino, A., Giuffrida, P., Corazza, G. R., Di Stefano, M., Caio, G., Latella, G., Ciacci, C., Fuschi, D., Mastroroberto, M., Bellacosa, L., Stanghellini, V., Volta, U., & Barbara, G. (Accepted/In press). Serum zonulin and its diagnostic performance in non-coeliac gluten sensitivity. Gut. https://doi.org/10.1136/gutjnl-2019-319281