Table 1.
Evidence for the Effect of Gluten-free Diet in Irritable Bowel Syndrome
| Author | Study design | Population | Intervention | Control diet | Outcome | Conclusion |
|---|---|---|---|---|---|---|
| Wahnschaffe et al, 200146 | Observational | 102 IBS-D; 41 CD; 30 controls | GFD for 6 months in 26 IBS-D | - | Stool frequency; immune markers (AGA, tTGA) in duodenal aspirate; IELs; HLA-DQ2 status (in all patients) | Improved stool frequency and decreased immune markers in duodenal aspirates of HLA-DQ2+ IBS-D patients after GFD |
| Wahnschaffe et al, 200747 | Observational | 145 IBS-D; 74 CD; 57 IBD | GFD for 6 months in 41 IBS-D | - | Stool frequency; serum immune markers (AGA, tTGA); HLA-DQ2 status | Improved stool frequency and decreased immune markers in HLA-DQ2+ IBS-D patients after GFD |
| Biesiekierski et al, 201148 | DB-randomized controlled trial | 34 IBS that improved on GFD for 6 wk; Marsh 0; 56% HLADQ2/8+ | Gluten challenge (bread/muffin) 16 g/ day for 6 wk | Gluten-free muffin/bread | GI symptoms; intestinal permeability; fecal lactoferrin | Gluten triggered gut symptoms and tiredness in 68% of IBS patients |
| Sapone et al, 201149 | Observational | 26 NCGS; 42 CD; 39 disease controls (dyspepsia) | GFD | - | GI and extra-intestinal symptoms; intestinal permeability | Gluten evoked innate immune activation in the absence of changes in mucosal barrier function |
| Carroccio et al, 201350 | DB-randomized controlled trial | 276 IBS with Marsh 0–1 and negative skin Prick IgE that improved with wheat withdrawal for 4 wk | Wheat challenge (capsules containing wheat) for 2 wk | Placebo (capsules containing xylose) for 2 wk | GI symptom changes according to VAS increase (> 20 mm) | 1/3 of IBS reacted to wheat challenge; wheat sensitive patients had eosinophil infiltration in duodenal and colonic mucosa |
| Biesiekierski et al, 201351 | DB-cross-over challenge | 22 IBS that improved on GFD for 6 wks; Marsh 0; 56% HLA-DQ2/8+ | 2-wk low-FODMAPs period, followed by high-gluten (16 g/day); 2-wk washout. Meals provided | Low-gluten (2 g/day) or (16 g whey protein/day) for 1 wk | GI symptom changes according to VAS increase (> 20 mm) | No evidence of specific or dose-dependent effects of gluten in IBS patients on previous low-FODMAPs diet |
| Vazquez-Roque et al, 201352 | Randomized controlled trial | 57 IBS-D screened; 45 IBS-D randomized (50% HLA-DQ2/8+) | 23 patients on GFD for 4 wk Meals provided | 22 patients on GCD for 4 wk | GI symptoms and transit; intestinal permeability; cytokine profile; TJ proteins | Gluten alters intestinal barrier in patients with in HLA-DQ2/8+ IBS-D patients |
| Rodrigo et al, 201453 | Observational | 97 IBS and fibromyalgia; 58 Marsh I and 39 Marsh 0 | GFD for 1 yr | - | Fibromyalgia questionnaire; health assessment questionnaire (SF36) | Symptom improvement in IBS/fibromyalgia patients after GFD |
| Di Sabatino et al, 201554 | DB-cross over challenge | 92 with suspected NCGS/NCWS responding to GFD; 61 randomized | Gluten challenge (capsules = 4.375 g/day) for 1 wk; 1-wk washout | Placebo (capsules containing rice starch) | GI and extraintestinal symptom changes according to VAS increase | Gluten evoked overall GI and extraintestinal symptom worsening in some NCGS patients |
| Zanini et al, 201555 | DB-cross-over challenge | 112 with suspected NCGS/NCWS; 53 enrolled; 35 actually challenged | Gluten containing flour for 10 days; 2-wk washout | Gluten-free flour | GSRS | Gluten challenge evoked symptom recurrence in 1/3 of NCGS/NCWS patients |
| Elli et al, 201656 | DB-cross-over challenge | 140 FGIDs; 101 responding to GFD; 98 actually enrolled and randomized | Gluten challenge (capsules = 5.6 g/day) for 1 wk | Placebo (capsules containing rice starch) | GI symptom changes according to VAS increase (> 3 cm); SF36 | Gluten challenge triggered symptom recurrence in 14% of patients with FGIDs |
IBS-D, diarrhea predominant irritable bowel syndrome; CD, celiac disease; GFD, gluten-free diet; AGA, anti-gliadin antibodies; tTGA, tissue transglutaminase antibodies; IELs, intra-epithelial lymphocytes; HLA, human leukocyte antigen; IBD, inflammatory bowel disease; DB, double blind; GI, gastrointestinal; NCGS, non-celiac gluten sensitivity; IBS, irritable bowel syndrome; IgE, immunoglobulin E; VAS, visual analogue scale; FODMAPs, fermentable oligo-, di-, and monosaccharides and polyols; GCD, gluten containing diet; TJ, tight junction; SF36, Short Form (36-item) questions health survey; NCWS, non-celiac wheat sensitivity; GSRS, gastrointestinal symptom rating scale; FGIDs, functional gastrointestinal disorders.