Table 3.

Main characteristics of the studies regarding gluten intake or use of a gluten free diet in FGIDs.

Study	Type of Study	Population	Aim	Results
Wahnschaffe et al. [79], 2007	Prospective interventional study	An amount of 145 IBS adult patients. 102 healthy controls	To evaluate the symptoms’ response to a GFD in IBS patients.	An amount of 41 IBS patients showed a significant decrease in stool frequency and GI symptom score, which in 49% of the patients improved within the normal range.
Biesiekierski et al. [21], 2011	Double-blind randomized placebo-controlled trial	An amount of 34 IBS adult patients, who ruled out CD.	Determine whether gluten ingestion could induce symptoms in non-celiac individuals affected by IBS	The majority (68%) of the patients who received gluten had higher severity scores over the entire study period and much greater changes in overall symptoms compared to the placebo group.
Vazquez-Roque et al. [80], 2013	Single-centre randomized controlled trial.	An amount of 45 IBS adult patients.	Evaluation of the impact of a four-week GFD randomly administered in IBS patients according to HLA haplotype.	Significant increase in stool frequency and small bowel permeability in the GCD group, especially in HLA-DQ2/8 positive subjects. No beneficial diet effect was observed on gastric emptying, colonic transit, and stool form.
Aziz et al. [76], 2016	Prospective interventional study.	An amount of 41 patients with IBS-D (20 HLA-DQ2/8 positive and 21 HLA-DQ2/8 negative).	Evaluation of the effects of a six-week GFD in patients with IBS-D, according toHLA haplotype.	Reduction of IBS Symptom Severity Score by 50 points in 29 patients (71%). The mean total IBS Symptom Severity Score decreased from 286 to 131 points after six weeks of diet (p < 0.001); the reduction was similar in each HLA-DQ group.
Zanwar et al. [78], 2016	Double-blind randomized placebo-controlled trial.	An amount of 60 IBS adult patients who ruled out CD and wheat allergy.	Evaluation of the effects of GFD in IBS patients. Subsequent gluten rechallenges after four weeks of washout in patients who positively responded.	In the first phase, overall symptom VAS score improved for 36% of patients after GFD. After four weeks of food rechallenge, patients in the gluten group presented worsening of symptoms, with higher weekly median overall symptom VAS, in contrast to those in the placebo group (p < 0.05) Patients who followed a gluten contained diet showed higher rates in terms of bloating, abdominal pain, and tiredness.
Elli et al. [74], 2016	Multi-centre randomized double-blind placebo-controlled study.	An amount of 140 FGIDs patients	Evaluation of the impact of GFD on FGIDs. Patients who positively responded to a strict three-week GFD underwent a placebo controlled double-blind gluten challenge with crossover	Up to 75% of the patients positively responded to the three-week GFD, showing an improvement of general wellbeing. After the placebo-controlled gluten challenge, 14% of these responder patients had an exacerbation of the symptoms, suggesting a NCGS diagnosis and a possible placebo effect of GFD
Barmeyer et al. [77], 2016	Prospective interventional study.	An amount of 35 IBS patients	Evaluation of the impact of a four-month GFD on IBS symptoms according to HLA haplotype.	An amount of 12 patients (34%) had significant symptoms and wellbeing improvement, showing no association with HLA-DQ2/8 expression.
Du et al. [73], 2017	Case-control study.	An amount of 101 newly diagnosed FD patients and 31 asymptomatic controls	Evaluation of the impact of gluten assumption on FD	The assumption of foods rich in gluten was higher in frequency (p = 0.047) and quantity (p = 0.01) in FD patients compared to controls. Early satiety (p = 0.03) and worsening of GI symptoms were associated with increased gluten consumption.
Shahbazkhani et al. [75], 2020	Randomized double-blind placebo controlled trial.	An amount of 77 patients with refractory FD.	Evaluating the effect of GFD in refractory dyspeptic patients. Patients who responded to the GFD underwent a double-blind placebo-controlled gluten challenge.	An amount of 35% of the patients positively responded to the GFD in terms of clinical improvement. An amount of 6.4% of the patients could be labelled as affected by NCGS, as they manifested symptoms after blind gluten ingestion.