Can Serum Zonulin Help Diagnose Non-Celiac Gluten Sensitivity?

Celiac.com 04/20/2021 - Non-celiac gluten sensitivity (NCGS) is marked by intestinal and extraintestinal symptoms triggered by gluten-containing foods, but with no celiac disease or wheat allergy. 

There are currently no known biomarkers to diagnose non-celiac gluten sensitivity, and the gold standard double-blind placebo-controlled gluten challenge is clinically impractical. 

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A team of researchers recently set out to investigate the role of serum zonulin as a diagnostic biomarker of NCGS and to develop a diagnostic algorithm.

The research team included 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, and Giovanni Barbara.

They are variously affiliated with the Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy, the First Department of Internal Medicine, San Matteo Hospital Foundation, University of Pavia, Italy; the Department of Clinical Medicine Public Health Life Sciences and Environment, University of L'Aquila, Italy; the Department of Medicine, Surgery, and Dentistry Scuola Medica Salernitana, University of Salerno, Salerno, Italy, and the Department of Medical and Surgical Sciences, University of Bologna, Italy.

For their multi-center study, the team enrolled 86 patients with either self-reported or double-blind confirmed non-celiac gluten sensitivity, 59 patients with diarrhea-predominant IBS (IBS-D), 15 patients with celiac disease, and 25 asymptomatic control subjects. 

The team assessed Zonulin serum levels, and calculated the associated diagnostic power. They recorded any clinical and symptomatic data. They also assessed the effect of diet on zonulin levels in a subgroup of patients with non-celiac gluten sensitivity.

Compared with asymptomatic control subjects, the non-celiac gluten sensitivity patients, regardless of diagnosis modality, and celiac patients showed substantially increased levels of zonulin, as did both non-celiac gluten sensitivity and celiac patients, compared with IBS-D patients. 

Self-reported non-celiac gluten sensitivity showed increased zonulin levels compared with double-blind confirmed and not-confirmed non-celiac gluten sensitivity. 

There's been a lot of talk about gluten-free diets benefiting non-celiac gluten sensitivity patients, but this study found that six-month wheat avoidance significantly reduced zonulin levels only in non-celiac gluten sensitivity patients with positive HLA-DQ2/8. Wheat withdrawal was associated with reduced zonulin levels only in non-celiac gluten sensitivity with the HLA genotype.

Zonulin levels were 81% accurate in distinguishing non-celiac gluten sensitivity from IBS-D. By excluding celiac disease, a diagnostic algorithm combining zonulin levels, symptoms and gender increased that accuracy to 89%.

Certainly finding a reliable new biomarker for non-celiac gluten sensitivity would be a big deal. This study shows that zonulin can be an accurate diagnostic biomarker for non-celiac gluten sensitivity. When combined with demographic and clinical data, Zonulin levels can differentiate non-celiac gluten sensitivity from IBS-D with high accuracy. 

Expect more investigation into the use of zonulin levels as an accurate diagnostic biomarker for non-celiac gluten sensitivity. If it pans out, expect to see it developed for clinical practice, though that may take some time.

Source: Gut, 2020 Nov;69(11):1966-1974.