Food allergy in irritable bowel syndrome: The case of non-celiac wheat sensitivity

Table 1 Summary of studies on irritable bowel syndrome and atopy

Ref.	Study design	Patients	Topic	Main results
White et al[83], 1991	Case-control observational study	11 IBS patients 11 healthy controls 11 organic gut diseases patients	IBS and bronchial hyper-responsiveness	FEV1 reduction induced by methacholine in IBS patients was significantly greater than that observed in healthy subjects. FEV1 decrease in patients with organic disease was not different from that in normal subjects
Yazar et al[84], 2001	Case-control observational study	133 IBS patients 137 healthy controls	IBS and asthma	Twenty-one (15.8%) IBS patients and 2 (1.45%) patients from the control group had the diagnosis of asthma. FEV1, flow after 50% of the vital capacity has been exhaled, peak expiratory flow rate, and maximal mid-expiratory flow rate were significantly different
Jun et al[85], 2005	Case-control observational study	42 IBS patients 42 healthy controls	IBS and bronchial hyper-responsiveness	No statistical difference was found between the two groups with respect to FEV1, FVC, FVC/FEV1, and FEF(25-75)
Roussos et al[86], 2003	Case-control observational study	150 asthma patients 130 other pulmonary disease patients 120 healthy controls	IBS and asthma	IBS prevalence was significantly higher in asthmatics (62/150, 41.3%) than in subjects with other pulmonary disorders (29/130, 22.3%) and healthy controls (25/120, 20.8%). None of the asthma medications were associated with increased or decreased likelihood of IBS
Ozol et al[87], 2006	Case-control observational study	125 asthma patients 95 healthy controls	IBS and asthma	IBS was found in 29.6% and 12.7% (P < 0.005) respectively of asthma patients and healthy controls. Food allergy was reported in 7.2% and 2.1% (P > 0.05) respectively for the two groups. No significant association between asthma related parameters, IBS, and food allergy could be found
Powell et al[88], 2007	Retrospective study	7235 patients attending a general practice	IBS, asthma and allergic rhinitis	IBS was more common in patients with asthma (9.9%) and allergic rhinitis (7.9%) compared to patients with chronic diseases (4.9%, P < 0.002 and 4.9%, P < 0.05 respectively) or the remaining non-asthmatic population (5.5%, P < 0.001 and 5.5%, P < 0.02 respectively)
Cole et al[89], 2007	Nested case-control study	91237 people with asthma 24518 people without asthma	IBS and asthma	Incidence of IBS among people with asthma was 20% higher than in non-asthmatic patients; no association was found between oral steroid intake and IBS among people with asthma
Huerta et al[90], 2002	Population-based cohort study	50000 people with asthma 50000 people without asthma	IBS and asthma	IBS incidence in the asthma cohort was 2.5 per 1000 persons/years and 2.0 in the general population, with a RR of 1.3. In the asthma cohort, oral steroid users had RR of 0.5 for developing IBS, without any difference between short- and long-term users
Panicker et al[91], 2008	Case-control observational study	138 asthma patients 145 healthy controls	IBS and asthma	A large proportion (39.13%) of asthmatics had IBS compared to controls (7.93%) (P < 0.001). IBS was reported in 87% of cases using inhalers, and in 13% with additional oral theophylline (P < 0.001). As many as 66.6% cases, had IBS with relatively short duration of asthma (1-5 yr, P < 000)
Hunskar et al[92], 2012	Cohort study	817 subjects exposed to giardia 1128 subjects not exposed to giardia	Post-infection IBS and asthma	IBS was found in 47.8% of subjects with asthma compared with 45.3% in those without asthma (P = 0.662) in the giardia exposed group. For controls, corresponding percentages were 23.9% and 12.2% (P < 0.001)
Tobin et al[93], 2008	Prospective study	125 consecutive: allergy/immunology (n = 39), gastroenterology (n = 36) general medicine (n = 50)	IBS and atopic diseases	The likelihood of IBS was significantly higher in patients with seasonal allergic rhinitis (2.67 times; P = 0.03), allergic eczema (3.85 times; P = 0.001), and depression (2.56 times; P = 0.04). Patients reporting atopic symptoms (seasonal allergic rhinitis, asthma, and allergic eczema) were 3.20 times (95%; P = 0.02) more likely to fulfill IBS criteria
Jones et al[94], 2014	Retrospective study	30000 patients from primary care medical records	FGIDs and atopic diseases	In patients suffering from IBS alone, functional dyspepsia alone and multiple functional gastrointestinal disorders, there was higher asthma prevalence compared to controls (OR = 1.43, 1.41 and 1.92 respectively)
Olén et al[96], 2014	Birth cohort study	2610 children	Recurrent abdominal pain and atopic diseases in children	237 (9%) children reported abdominal pain when 12 yr old. Asthma in the first two years of life and food allergy at age 8 yr were significantly associated with abdominal pain at 12 yr (P < 0.001). There was an increased risk of abdominal pain at 12 yr in children sensitized to food allergens at 4 or 8 yr
Smith et al[97], 1985	Prospective study	29 patients with perceived food hypersensitivity	Self-reported food hypersensitivity and allergy	17 (60%) of the 26 patients were positive to skin prick tests to inhalant allergens
Lillestøl et al[98], 2010	Prospective study	71 patients with perceived food hypersensitivity	Self-reported food hypersensitivity and allergy	66 (93%) patients suffered from IBS and 43 (61%) had atopic diseases (predominantly rhinoconjunctivitis). Atopic patients had increased density of IgE-bearing cells and intestinal permeability but gastrointestinal symptoms did not differ between groups (P = 0.02). IgE-positive cells and intestinal permeability did not differ between patients who were sensitized to inhalants and those who were only sensitized to food
Berstad et al[99], 2012	Prospective study	84 patients with perceived food hypersensitivity	Self-reported food hypersensitivity, IBS, chronic fatigue and fibromyalgia	83 patient were diagnosed with IBS, 58% with severe symptoms. 85% reported symptoms suggestive of chronic fatigue and 71% fibromyalgia. These symptoms could not be explained either by IgE-mediated food allergy or by organic pathology
Lind et al[100], 2013	Case-control observational study	38 patients with self-reported food allergy 42 healthy controls	Self-reported food hypersensitivity, IBS, fatigue	FIS scores were higher in patients (median 85.0, interquartile range 36.8-105.3) than in controls (median 14.0, interquartile range 3.0-29.0, P ≤ 0.0001)
McKee et al[12], 1987	Observational study	40 IBS patients	IBS and elimination diet	Patients received an antigen-exclusion. 15% showed improvement in their IBS-symptoms. A further 12.5% reported increased well-being but this did not seem to be related to the exclusion of any particular food. The diarrhea prevalent subgroup responded the best (3/8) whereas the constipation subgroup consistently failed to improve
Heizer et al[17], 2009	Review	NA	IBS and elimination diet	25% of IBS patients reported their symptoms may be caused or exacerbated by one or more dietary components. Diet restricted in fermentable, poorly absorbed carbohydrates, including fructose, fructans, sorbitol, and other sugar alcohols seemed to be beneficial
Zar et al[101], 2005	Prospective study	25 IBS patients	IBS and elimination diet	Patient IgG4 antibodies to milk, eggs, wheat, beef, pork and lamb were measured, and were commonly elevated. Significant improvement was reported in pain severity (P < 0.001), pain frequency (P = 0.034), bloating severity (P = 0.001), satisfaction with bowel habits (P = 0.004) and effect of IBS on life in general (P = 0.008) at 3 and 6 mo of elimination diet
Atkinson et al[102], 2004	Randomized trial	150 IBS patients	IBS and elimination diet	Patients received either a diet excluding all foods to which they had raised IgG antibodies or a sham diet for 3 mo. The true diet resulted in a 10% (26% in fully compliant) greater reduction in symptom score than the sham diet
Bolin[103], 1980	Randomized trial	20 patients suffering from persistent diarrhea	IBS and DSCG	18 patients reported significant improvement in diarrhea while taking sodium cromoglycate and this did not correlate with the presence of other atopic diseases, history of food intolerance, or lactase deficiency
Paganelli L et al[104], 1990	Prospective study	14 IBS patients	IBS, elimination diet and DSCG	7 (50%) patients improved after elimination diet with (5/7) and without (2/5) DSCG
Lunardi et al[105], 1991	Double-blind cross-over trial	20 IBS patients	IBS and DSCG	18 patients completed the study; analysis of patients' diary card scores showed a statistically significant difference in favor of DSCG
Stefanini et al[106], 1992	Prospective study	101 IBS patients (diarrhea type)	IBS, atopy and DSCG	Patients were then tested for 48 commercial alimentary antigens by SPT and underwent 8 wk of oral DSCG. Symptom improvement was observed in 67% of the 74 SPT-positive patients, whereas only in 41% of the 27 SPT-negative patients
Stefanini et al[107], 1995	Multicenter trial	428 IBS patients (diarrhea type)	IBS, elimination diet and DSCG	IBS symptoms improved in 60% of patients treated with elimination diet and in 67% of those treated with DSCG. In both groups clinical results were significantly better in the patients positive to the skin prick test than in the negative ones
Leri et al[108], 1997	Randomized study	120 IBS patients (diarrhea type)	IBS, elimination diet and DSCG	66 patients had positive SPT; they were randomly treated with elimination diet (30) or with elimination diet plus DSCG. 18 (60%) of the 30 patients that had received the only exclusion diet reported symptom improvement, whereas 32 of the 36 patients (89%) who had undergone both dietary and DSCG treatments showed an improvement that was clinically and statistically significant (P = 0.01)

DSCG: Disodium cromoglycate; FCV: Forced vital capacity; FEF: Forced expiratory flow; FEV1: Forced expiratory volume in 1 s; FGIDs: Functional gastrointestinal disorders; FIS: Fatigue impact scale; IBS: Irritable bowel syndrome; RR: Relative risk; SPT: Skin prick test; NA: Not available.