Evaluation of Non-Celiac Gluten Sensitivity in Patients with Previous Diagnosis of Irritable Bowel Syndrome: A Randomized Double-Blind Placebo-Controlled Crossover Trial

Michele Barone, Eugenio Gemello, Maria Teresa Viggiani, Fernanda Cristofori, Caterina Renna, Andrea Iannone, Alfredo Di Leo, Ruggiero Francavilla, Michele Barone, Eugenio Gemello, Maria Teresa Viggiani, Fernanda Cristofori, Caterina Renna, Andrea Iannone, Alfredo Di Leo, Ruggiero Francavilla

Abstract

Background. To date, there is no reliable marker for the diagnosis of non-celiac gluten sensitivity (NCGS), which benefits from a gluten-free diet (GFD). This condition is characterized by functional gastrointestinal symptoms similar to those occurring in the course of irritable bowel syndrome (IBS). However, IBS has a higher prevalence, and often benefits from the administration of a low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet. The overlap of symptoms between these two pathologies has led to an overestimation of self-made diagnosis NCGS. Aims. To better identify NCGS in subjects with a previous diagnosis of IBS. Methods. All subjects received a low FODMAP diet that was also gluten-free (low FODMAP-GFD), and those presenting an improvement of symptoms were exposed to gluten or placebo (double-blind challenge with wash-out and crossover). The response to dietary treatments was evaluated by visual analogue scale (VAS). Results. Of 30 patients (23 women, seven men, aged 42.2 ± 12.5 years, body mass index (BMI ) 24.7 ± 4.1 kg/m2), 26 benefited from the administration of low FODMAP-GFD and were exposed to the gluten/placebo challenge. After the challenge, using an increase of visual analogue scale VAS (Δ-VAS) ≥30%, 46.1% of the patients were NCGS+. However, this percentage became only 19.2% using a different method (mean ∆-VAS score plus two standard deviations). Conclusions. FODMAP intolerance could hide the response to a challenge test with gluten for the identification of NCGS in IBS patients. A low FODMAP-GFD followed by gluten/placebo challenge is able to identify patients with NCGS better. ClinicalTrials.gov registration number NCT04017585.

Keywords: FODMAP; gluten challenge; gluten-free diet.

Conflict of interest statement

The authors report no conflict of interest.

Figures

Figure 1
Figure 1
A detailed description of the three phases of the study.
Figure 2
Figure 2
Flow diagram describing the process from assessment for eligibility through the completion of the study. IBS, irritable bowel syndrome; FODMAP, fermentable oligosaccharides, disaccharides, monosaccharides and polyols; VAS, visual analogue scale.
Figure 3
Figure 3
Graphical representation of the VAS score changes from the beginning to the end of the study. Black continuous lines refer to the phases with low FODMAP-GFD and red and blue continuous lines correspond to the gluten and rice challenge, respectively. The ends of each dotted line represent the mean of the VAS values obtained at the beginning and the end of each phase of the study.
Figure 4
Figure 4
Distribution of patients according to their VAS score while on gluten and placebo. Patients closer to the diagonal dashed line had a similar response to gluten and placebo. The two patients located in the lower right square but not included in the ellipse experienced a mild degree of the overall response. Patients included in the ellipse had a significant increase in VAS score ≥5.0 cm after gluten challenge (for the calculation of this value refer to the “Materials and Methods” section). The risk of symptom worsening after gluten assumption was increased by five times (95% CI 0.63 to 39.91) compared to placebo, although such a difference did not reach statistical significance. The absolute risk difference was 15% (95% CI − 1% to 32%).

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