Table 2.
Studies assessing the role of gluten in patients with IBS and/or non-celiac gluten (or wheat) sensitivity.
| Study (Year) Country | Design, Population (n) | Interventions | Main Findings |
|---|---|---|---|
| Dale et al. (2018) Norway [89] | RDBPC, cross-over trial NCGS patients on a GFD (n = 20) | GFD vs. GCD, 4 challenges (2 gluten, 2 placebo) 4 days per intervention, 3 days washout. (muffins with gluten 11 g/day vs. gluten-free muffins) | No significant differences in symptom severity between gluten and placebo challenges. High symptom scores during all challenges. |
| Skodje et al. (2018) Norway [88] | RDBPC, cross-over trial self-reported NCGS patients on GFD >6 months (n = 59) | GFD (placebo) vs. GCD (5.7 g/day) vs. Fructans (2.1 g/day), 1 week per intervention, 1 week washout. (concealed muesli bars). | Significant differences in GI symptoms between all interventions. Fructans: overall GI symptoms and bloating significantly higher than gluten. |
| Picarelli et al. (2016) Italy [90] |
RDBPC trial, NCGS patients (n = 26) | GFD vs. GCD, 1 day. (croissant with 10 g of gluten vs. gluten-free croissant) | No significant difference in overall symptom severity between gluten and placebo challenge. |
| Aziz et al. (2016) UK [91] |
Open label, IBS-D patients (n = 41) | GFD, 6 weeks (information and advice GFD by dietician) | Decrease of symptoms in >70% of patients, significant after 2 weeks, similar results in HLA-DQ positive and negative |
| Elli et al. (2016) Italy [92] |
RDBPC, cross-over trial, IBS patients with NCGS (n = 98) | GFD vs. GCD, 1 week per intervention, 1 week washout (gastro-soluble capsules with 5.6 g/day gluten powder or placebo). Run-in period of 3 weeks GFD. | 14% of patients that responded to gluten withdrawal had symptomatic relapse during gluten challenge. |
| Shahbazkhani et al. (2015) Iran [93] |
DB RCT, IBS patients (n = 148) | GFD vs. GCD, 6 weeks (packages with 52 g/day gluten powder, or rice starch as placebo). Run-in period of 6 weeks. | Significant improvement in overall symptom severity GFD (83.8%) vs. GCD (25.7%). |
| Di Sabatino et al. (2015) Italy [94] |
RDBPC, cross-over trial, suspected NCGS patients (n = 61) | GFD vs. GCD, 1 week per intervention, 1 week washout. (gastro-soluble capsules with 4.4 g/day gluten vs. rice starch) | Significant increase in overall symptom severity during gluten compared to placebo. Abdominal bloating, pain and (extra)-intestinal symptoms significantly more severe during gluten-period. |
| Peters et al. (2014) Australia [95] | RDBPC, cross-over trial NCGS patients (n = 22) | Gluten (16 g/day) vs. Whey (16 g/day) vs. Placebo, 3 days per intervention, at least 3 days washout. (provided meals with 16 g/day whey protein vs. placebo) | No significant differences in GI symptoms between interventions. Significant more feelings of depression due to short-term exposure to gluten. |
| Vazquez-Roque et al. (2013) USA [96] |
RCT, IBS-D patients (n = 45) | GFD vs. GCD, 4 weeks (standardized meals provided by metabolic kitchen, with or without gluten) | Significant increase in stool frequency GCD vs. GFD. Greater difference in HLA-DQ positive patients. |
| Biesiekierski et al. (2013) Australia [86] |
(1) RDBPC, cross-over trial, IBS patients with NCGS (n = 40) (2) Rechallenge, IBS patients with NCGS (n = 22) |
(1) High gluten (16 g/day) vs. Low gluten (2 g/day) vs. Whey (16 g/day), 1 week per intervention. (2) Gluten (16 g/day) vs. Whey (16 g/day) vs. Placebo (no additional protein), 3 days. Run-in period of 2 weeks, GFD and low FODMAP diet |
Symptom improvement in all patients during run-in period (low FODMAP, gluten-free). Symptom deterioration in all groups, no specific gluten dose response. |
| Carroccio et al. (2012) Italy [97] |
RDBPC, cross-over trial, suspected NCGS patients (n = 920) | Wheat (20 g/day) vs. Xylose (placebo), 2 weeks per intervention, at least 1 week washout. (gastro-soluble capsules). Elimination diet of 4 weeks prior to challenge. | Symptom improvement of at least 30% in wheat-free period (Salerno experts’ criteria): NCGS diagnosis was confirmed in 30% (n = 276) of subjects. |
| Biesiekierski et al. (2011) Australia [98] |
RCT, IBS patients (n = 39) | GFD vs. GCD, 6 weeks (Muffin and bread with or without gluten, 16 g/day) | GCD baseline vs. 1 week: significant increase in overall symptom severity, as well as bloating, abdominal pain, tiredness, dissatisfaction with stool. GCD vs. GFD, 6 weeks: significant increase in severity of abdominal pain, tiredness and dissatisfaction with stool. |
Abbreviations: DB: double-blind; FODMAPs: fermentable, oligo-, di-, monosaccharides and polyols; GCD: gluten-containing diet; GFD: gluten-free diet; GI: gastrointestinal; HLA-DQ: human leukocyte antigen-DQ; IBS: irritable bowel syndrome; IBS-D: irritable bowel syndrome with predominant diarrhea; NCGS: non-celiac gluten (or wheat) sensitivity; RCT: randomized, controlled trial; RDBPC: randomized, double-blind, placebo-controlled.