Whole Cow's Milk but Not Lactose Can Induce Symptoms in Patients with Self-Reported Milk Intolerance: Evidence of Cow's Milk Sensitivity in Adults.

BACKGROUND: Lactose intolerance is the most frequent food intolerance, but many subjects with self-reported milk intolerance (SRMI) are asymptomatic at lactose hydrogen breath test (LHBT). The aim of this study was to evaluate the frequency of lactose intolerance in SRMI patients and their clinical characteristics. METHODS: In a retrospective study, the clinical records of 314 SRMI patients (259 females, mean age: 39.1 ± 13.5 years) were reviewed; 102 patients with irritable bowel syndrome (IBS) served as controls. In a prospective study, 42 SRMI patients, negatives at the LHBT, underwent a double-blind, placebo-controlled (DBPC) whole cow's milk challenge. RESULTS: In the retrospective study, only 178 patients (56%) were lactose maldigesters and intolerant at LHBT; 68% of the subjects with SRMI were suffering from IBS; 74% reported dyspepsia (p = 0.0001 vs. IBS controls); and weight loss was recorded in 62 SRMI patients (20%) (p = 0.01 vs. IBS controls). Duodenal histology showed intra-epithelial lymphocytosis in about 60% of cases. In the prospective study, 36 patients (86%) experienced symptoms during the DBPC cow's milk challenge, and only 4 patients (9%) reacted to placebo (p = 0.0001). CONCLUSIONS: A percentage of SRMI patients were not suffering from lactose intolerance. DBPC revealed that SRMI patients had clinical reactions when exposed to whole cow's milk.

WHOLE-meal ancient wheat-based diet: Effect on metabolic parameters and microbiota.

BACKGROUND & AIMS: Ancient wheat varieties are considered to be healthier than modern ones, but the data are not univocal. We investigated changes in hematochemical parameters and evaluated microbiota data before and after a set period on a diet containing a whole-meal ancient wheat mix. PATIENTS AND METHODS: 29 cloistered nuns were recruited. The study comprised two consecutive 30-day periods; during the first one (T1), the nuns received wheat-based foods produced with refined "modern" flour ("Simeto"); during the second one (T2) received wheat-based foods produced with an unrefined flour mix composed of "ancient" cultivars. At entry to the study (T0) and at the end of T1 and T2 hematochemical parameters and fecal microbiota and metabolome were evaluated. RESULTS: At the end of T2, there was a significant reduction in serum iron, ferritin, creatinine, sodium, potassium, magnesium, total cholesterol, LDL- and HDL-cholesterol and folic acid. Furthermore, increased the abundance of cultivable enterococci, lactic acid bacteria and total anaerobes. The ability of the gut microbiome to metabolize carbohydrates increased after the period of diet containing ancient grain products. Several volatile organic compounds increased after the one month on the diet enriched with ancient grain products. CONCLUSIONS: Our data showed the beneficial effects deriving from a diet including ancient whole-meal/unrefined wheat flours.

Gynecological Disorders in Patients with Non-celiac Wheat Sensitivity.

BACKGROUND: Non-celiac wheat sensitivity (NCWS) most frequently presents clinically with irritable bowel syndrome (IBS)-like symptoms, although many extra-intestinal manifestations have also been attributed to it. No studies to date have evaluated the presence and frequency of gynecological symptoms in NCWS. AIM: To evaluate the frequency of gynecological disorders in patients with NCWS. PATIENTS AND METHODS: Sixty-eight women with NCWS were included in the study. A questionnaire investigating gynecological symptoms and recurrent cystitis was administered, and patients reporting symptoms were then examined by specialists. Three control groups were selected: 52 patients with IBS not related to NCWS, 56 patients with celiac disease (CD), and 71 healthy controls. RESULTS: 59% of the patients with NCWS showed gynecological symptoms, a higher frequency than in healthy controls (P = 0.04), IBS controls (P = 0.01) and CD controls (P = 0.02). Menstrual cycle alterations were more frequent in patients with NCWS than in healthy controls (26.5% vs 11.3%; P = 0.03); the patients with NCWS suffered from recurrent vaginitis (16%) and dyspareunia (6%) significantly more frequently than healthy controls. Twenty-nine percent of patients with NCWS reported recurrent cystitis, a finding higher than in the control groups (vs healthy P = 0.0001, vs IBS P = 0.001, vs CD controls P = 0.04). Microbiological examinations were negative in most of the patients with NCWS and recurrent vaginitis or cystitis. During the 1-year follow-up, 46% of patients with menstrual disorders and 36% with recurrent vaginitis reported resolution of symptoms on a wheat-free diet. CONCLUSIONS: Patients with NCWS showed a significantly higher frequency of gynecological symptoms and recurrent cystitis than patients with IBS.

Autoimmunity Features in Patients With Non-Celiac Wheat Sensitivity.

INTRODUCTION: Nonceliac wheat sensitivity (NCWS) is characterized by intestinal and extraintestinal manifestations consequent to wheat ingestion in subjects without celiac disease and wheat allergy. Few studies investigated the relationship between NCWS and autoimmunity. The aim of this study is to evaluate the frequency of autoimmune diseases (ADs) and autoantibodies in patients with NCWS. METHODS: Ninety-one patients (13 men and 78 women; mean age of 40.9 years) with NCWS, recruited in a single center, were included. Seventy-six healthy blood donors (HBD) and 55 patients with a diagnosis of irritable bowel syndrome (IBS) unrelated to NCWS served as controls. Autoantibodies levels were measured. Human leukocyte antigen haplotypes were determined, and duodenal histology performed in all patients carrying the DQ2/DQ8 haplotypes. Participants completed a questionnaire, and their medical records were reviewed to identify those with ADs. RESULTS: Twenty-three patients with NCWS (25.3%) presented with ADs; autoimmune thyroiditis (16 patients, 17.6%) was the most frequent. The frequency of ADs was higher in patients with NCWS than in HBD (P = 0.002) and in patients with IBS (P = 0.05). In the NCWS group, antinuclear antibodies tested positive in 71.4% vs HBD 19.7%, and vs patients with IBS 21.8% (P < 0.0001 for both). The frequency of extractable nuclear antigen antibody (ENA) positivity was significantly higher in patients with NCWS (21.9%) than in HBD (0%) and patients with IBS (3.6%) (P = 0.0001 and P = 0.004, respectively). Among the patients with NCWS, 9.9% tested positive for antithyroglobulin, 16.5% for antithyroid peroxidase, and 14.3% for antiparietal cell antibodies; frequencies were not statistically different from controls. The presence of ADs was related to older age at NCWS diagnosis, female sex, duodenal lymphocytosis, and eosinophil infiltration. DISCUSSION: One in 4 patients with NCWS suffered from AD, and serum antinuclear antibodies were positive in a very high percentage of cases. These data led us to consider NCWS to be associated to ADs.

TNF-α, IL-17, and IL-22 production in the rectal mucosa of nonceliac wheat sensitivity patients: role of adaptive immunity.

In recent years, a new gluten- or wheat-related disease has emerged, a condition labeled "nonceliac gluten sensitivity" (NCGS) or "nonceliac wheat sensitivity" (NCWS). NCWS pathogenesis is still uncertain and attributed to very different mechanisms. We aimed to study the different T-lymphocyte subsets in the rectal mucosa of NCWS patients to demonstrate the possible contribution of adaptative immune response. Twelve patients (11 women, 1 man, age range 23-61 yr, median 32 yr) with a definitive diagnosis of NCWS were recruited at random for the present study. They underwent rectal endoscopy with multiple mucosal biopsies at the end of a double-blind placebo-controlled (DBPC) wheat challenge when they reported the reappearance of the symptoms. As controls we included 11 "healthy patients", sex- and age-matched with the patients who underwent colonoscopy evaluation for rectal bleeding due to hemorrhoids. Cells freshly obtained from rectal tissue were stained to detect anti-CD45, anti-CD3, anti-CD4, and anti-CD8. Furthermore, intracellular staining was performed with anti-tumor necrosis factor (TNF)-α, anti-interleukin (IL)-17, and anti-IL-22. Production of TNF-α by CD45+, CD3+, CD4+, and CD8+ cells, as well as of IL-17 by CD4+ cells, was higher in the rectal tissue of NCWS patients than in controls. On the contrary, IL-22 production by CD8+ cells was lower in NCWS patients than in the controls. In NCWS patients diagnosed by DBPC wheat challenge, there is a complex immunological activation, with a significant role for the adaptive response.NEW & NOTEWORTHY Nonceliac wheat sensitivity (NCWS) is a syndrome characterized by symptoms triggered by gluten intake. The pathogenesis is still uncertain. Studies have shown a role for innate immunity. We demonstrated that production of TNF-α by CD45+, CD3+, CD4+, and CD8+ cells and of IL-17 by CD4+ cells is higher in the rectal tissue of NCWS patients than in controls. We clearly demonstrated that in patients with NCWS there is a significant role for the adaptive response.

Body Mass Index and Associated Clinical Variables in Patients with Non-Celiac Wheat Sensitivity.

BACKGROUND: Non-Celiac Wheat Sensitivity (NCWS) is still a largely undefined condition, due to the lack of a diagnostic marker. Few data are available about the nutritional characteristics of NCWS patients at diagnosis. AIMS: To evaluate the proportion of NCWS patients who were underweight, normal weight, overweight, or obese at diagnosis, and to search for possible correlations between their Body Mass Index (BMI) and other NCWS-related disease characteristics. PATIENTS AND METHODS: The clinical charts of 145 NCWS patients (125 F, 20 M, mean age 37.1 ± 11.4 years), diagnosed between January 2012 and March 2018, were reviewed. As a comparison, 84 celiac disease (CD) patients (73 F, 11 M, mean age 39.8 ± 13.9 years) were evaluated. All NCWS diagnoses were based on a double-blind placebo-controlled wheat challenge (DBPCWC) method. RESULTS: BMI distribution was similar in the NCWS (6.2% underweight and 15.2% obese subjects) and CD patients (6% underweight and 7.1% obese subjects). Underweight NCWS subjects were significantly younger and had a shorter clinical history than the overweight or obese ones. Unlike the other NCWS patients, none of them had a DQ2 and/or DQ8 haplotype. Overweight and obese NCWS patients were more frequently suffering from associated autoimmune diseases than the other BMI categories (P = 0.05). Compared to the CD controls, NCWS patients showed a higher frequency of Irritable Bowel Syndrome (IBS)-like (P = 0.01) and extraintestinal symptoms (P = 0.03) and a longer clinical history (P = 0.04), whereas weight loss was more frequent in CD (P = 0.02). CONCLUSIONS: NCWS patients showed a BMI distribution similar to CD patients. However, NCWS was found to be a heterogenous condition that regards BMI, and clinical characteristics differed between the underweight and overweight/obese patients.

Abdominal Ultrasound Does Not Reveal Significant Alterations in Patients With Nonceliac Wheat Sensitivity.

GOALS: The goal of this study was (A) to evaluate abdominal ultrasound signs in nonceliac wheat sensitivity (NCWS) patients for features useful in diagnosis and (B) to compare these aspects with those of celiac patients to assess whether ultrasound can be useful in the differential diagnosis between NCWS and celiac disease (CD). BACKGROUND: NCWS diagnosis is difficult as no biomarkers of this condition have as yet been identified. In CD ultrasound aspects have been identified that have a good diagnostic accuracy. STUDY: We prospectively recruited 45 NCWS patients (11 males, 34 females; mean age 35.7 y). Three control groups were included: (A) 99 age-matched CD patients; (B) 18 patients with seronegative CD; (C) 50 patients with irritable bowel syndrome (IBS) who did not improve on a wheat-free diet. NCWS diagnosis was confirmed on the basis of an elimination diet and double-blind placebo-controlled (DBPC) challenge. Ultrasound sign investigation included: dilatation of the small bowel loops, thickening of the small bowel wall, hyperperistalsis, enlarged mesenteric lymph nodes, ascites, hyposplenism, altered diameter of the portal vein. RESULTS: NCWS patients showed a low frequency of pathologic ultrasound findings. Dilated or thickened loops appeared more often in CD patients than in NCWS patients (88.8% vs. 20%; P<0.0001). These US signs were significantly more frequent in seronegative CD than in NCWS patients (both P<0.0001), whereas no difference was found between NCWS patients and IBS controls. CONCLUSIONS: In NCWS patients' ultrasound does not show a characteristic pattern which could be helpful for diagnosis. However, US can be useful to differentiate between NCWS and CD patients and especially those with seronegative CD. (ClinicalTrials.gov NCT03017274).

Duodenal and Rectal Mucosa Inflammation in Patients With Non-celiac Wheat Sensitivity.

BACKGROUND & AIMS: Studies of non-celiac gluten or wheat sensitivity (NCGWS) have increased but there are no biomarkers of this disorder. We aimed to evaluate histologic features of colon and rectal tissues from patients with NCGWS. METHODS: We performed a prospective study of 78 patients (66 female; mean age, 36.4 years) diagnosed with NCGWS by double-blind wheat challenge at 2 tertiary care centers in Italy, from January 2015 through September 2016. Data were also collected from 55 patients wither either celiac disease or self-reported NCGWS but negative results from the wheat-challenge test (non-NCGWS controls). Duodenal and rectal biopsies were collected and analyzed by immunohistochemistry to quantify intra-epithelial CD3+ T cells, lamina propria CD45+ cells, CD4+ and CD8+ T cells, mast cells, and eosinophils and to determine the presence and size of lymphoid nodules in patients with NCGWS vs patients with celiac disease or non-NCGWS controls. RESULTS: Duodenal tissues from patients with NCGWS had significantly higher numbers of intra-epithelial CD3+ T cells, lamina propria CD45+ cells, and eosinophils than duodenal tissues from non-NCGWS controls. Duodenal tissues from patients with NCGWS and dyspepsia had a higher number of lamina propria eosinophils than patients with NCGWS without upper digestive tract symptoms. Rectal mucosa from patients with NCGWS had a larger number of enlarged lymphoid follicles, intra-epithelial CD3+ T cells, lamina propria CD45+ cells, and eosinophils than rectal mucosa from non-NCGWS controls. Duodenal and rectal mucosal tissues from patients with celiac disease had more immunocytes (CD45+ cells, CD3+ cells, and eosinophils) than tissues from patients with NCGWS or non-NCGWS controls. CONCLUSIONS: We identified markers of inflammation, including increased numbers of eosinophils, in duodenal and rectal mucosa from patients with NCGWS. NCGWS might therefore involve inflammation of the entire intestinal tract. Eosinophils could serve as a biomarker for NCGWS and be involved in its pathogenesis. Clinicaltrials.gov: NCT01762579.

Self-Reported Non-Celiac Wheat Sensitivity in High School Students: Demographic and Clinical Characteristics.

BACKGROUND: Non-Celiac Wheat Sensitivity (NCWS) has recently been included among the gluten-related disorders. As no biomarkers of this disease exist, its frequency has been estimated based on self-reported symptoms, but to date no data are available about self-reported NCWS in teenagers. AIM: To explore the prevalence of self-reported NCWS in a group of high school students and to study their demographic and clinical characteristics. METHODS: The study was performed between April 2015 and January 2016 in two high schools of a coastal town in the south of Sicily (Italy). A total of 555 students (mean age 17 years, 191 male, 364 female) completed a modified validated questionnaire for self-reported NCWS. The subjects who self-reported NCWS were then compared with all the others. RESULTS: Seven individuals (1.26%) had an established diagnosis of CD. The prevalence of self-reported NCWS was 12.2%, and 2.9% were following a gluten-free diet (GFD). Only 15 out of 68 (23%) NCWS self-reporters had consulted a doctor for this problem and only nine (14%) had undergone serological tests for celiac disease. The NCWS self-reporters very often had IBS symptoms (44%). CONCLUSIONS: Self-reported NCWS was found to be common in teenagers, with a frequency of 12.2%; the frequency of GFD use was 2.9%, which was much higher than the percentage of known CD in the same population (1.26%). A greater awareness of the possible implications on the part of the subjects involved, and a more thorough medical approach to the study of self-reported wheat-induced symptoms are required.

Persistence of Nonceliac Wheat Sensitivity, Based on Long-term Follow-up.

We investigated how many patients with a diagnosis of nonceliac wheat sensitivity (NCWS) still experienced wheat sensitivity after a median follow-up time of 99 months. We collected data from 200 participants from a previous study of NCWS, performed between July and December 2016 in Italy; 148 of these individuals were still on a strict wheat-free diet. In total, 175 patients (88%) improved (had fewer symptoms) after a diagnosis of NCWS; 145 of 148 patients who adhered strictly to a gluten-free diet (98%) had reduced symptoms, compared with 30 of 52 patients who did not adhere to a gluten-free diet (58%) (P < .0001). Of the 22 patients who repeated the double-blind, placebo-controlled challenge, 20 reacted to wheat. We conclude that NCWS is a persistent condition. Clinicaltrials.gov registration number: NCT02823522.

Contact Dermatitis Due to Nickel Allergy in Patients Suffering from Non-Celiac Wheat Sensitivity.

BACKGROUND:  Non-celiac wheat sensitivity (NCWS) is a new clinical entity in the world of  gluten-related diseases. Nickel, the most frequent cause of contact allergy, can be found in wheat  and results in systemic nickel allergy syndrome and mimics irritable bowel syndrome (IBS).  Objective: To evaluate the frequency of contact dermatitis due to nickel allergy in NCWS patients  diagnosed by a double-blind placebo-controlled(DBPC)challenge,and to identify  the  characteristics  of  NCWS  patients  with  nickel  allergy.  Methods: We performed  a prospective study  of 60 patients (54 females, 6 males; mean age 34.1 ± 8.1 years) diagnosed with NCWS from  December  2014 to November 2016; 80 age- and sex-matched subjects with functional gastrointestina l symptoms served as controls. Patients reporting contact dermatitis related to nickel-containing objects  underwent  nickel  patch  test  (Clinicaltrials.gov  registration number: NCT02750735). RESULTS:   Six  out  of  sixty  patients  (10%)  with  NCWS  suffered  from contact dermatitis and  nickel allergy  and  this  frequency  was  statistically  higher (p = 0.04)than observed in the control group(5%. The main clinical characteristic of  NCWS  patients with nickel allergy was a  higher frequency  of  cutaneous  symptoms  after  wheat ingestion compared to NCWS patients who did not suffer  from  nickel  allergy  (p < 0.0001. CONCLUSIONS:  Contact dermatitis and nickel allergy  are more  frequent  in  NCWS  patients than  in  subjects  with  functional gastrointestinal disorders;furthermore, these patients had a very high frequency of cutaneous manifestations after wheat  ingestion.  Nickel  allergy  should  be  evaluated  in  NCWS  patients  who  have  cutaneous  manifestations after wheat ingestion.

Predominance of Type 1 Innate Lymphoid Cells in the Rectal Mucosa of Patients With Non-Celiac Wheat Sensitivity: Reversal After a Wheat-Free Diet.

OBJECTIVES: Non-celiac wheat sensitivity (NCWS) is defined as a reaction to ingested wheat after exclusion of celiac disease and wheat allergy. As its pathogenesis is incompletely understood, we evaluated the inflammatory response in the rectal mucosa of patients with well-defined NCWS. METHODS: The prospective study included 22 patients with irritable bowel syndrome (IBS)-like clinical presentation, diagnosed with NCWS by double-blind placebo-controlled challenge. Eight IBS patients not improving on wheat-free diet were used as controls. Two weeks after oral challenge was performed with 80 grams of wheat daily, cells were isolated from rectal biopsies and thoroughly characterized by fluorescence-activated cell sorting analysis for intracellular cytokines and surface markers. RESULTS: Rectal biopsies from wheat-challenged NCWS patients showed that a significant mucosal CD45(+) infiltrate consisted of CD3(+) and CD3(-) lymphocytes, with the latter spontaneously producing more interferon (IFN)-γ than IBS controls. About 30% of IFN-γ-producing CD45(+) cells were T-bet(+), CD56(-), NKP44(-), and CD117(-), defining them as a type-1 innate lymphoid cells (ILC1). IFN-γ-producing ILC1 cells significantly decreased in 10 patients analyzed 2 weeks after they resumed a wheat-free diet. CONCLUSIONS: These data indicate that, in patients with active NCWS, IFN-γ-producing ILC1 cells infiltrate rectal mucosa and support a role for this innate lymphoid cell population in the pathogenesis of NCWS.

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

Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorders, having a prevalence of 12%-30% in the general population. Most patients with IBS attribute their symptoms to adverse food reactions. We review the role of diet in the pathogenesis of IBS and the importance of dietary factors in the management of these patients. The MEDLINE electronic database (1966 to Jan 2015) was searched using the following keywords: "food", "diet", "food allergy", "food hypersensitivity", "food intolerance", "IBS", "epidemiology", "pathogenesis", "pathophysiology", "diagnosis", "treatment". We found 153 eligible papers; 80 were excluded because: not written in English, exclusive biochemical and experimental research, case reports, reviews, and research otherwise not relevant to our specific interest. We selected 73 papers: 43 original papers, 26 reviews and 4 letters to the editor. These papers focused on IBS pathogenesis, the association between IBS and atopy, and between IBS and food allergy, the relationship between IBS and non-celiac wheat sensitivity, the role of diet in IBS. Pending further scientific evidence, a cautious approach is advisable but the concept of food allergy should be included as a possible cause of IBS, and a dietary approach may have a place in the routine clinical management of IBS.

High Proportions of People With Nonceliac Wheat Sensitivity Have Autoimmune Disease or Antinuclear Antibodies.

BACKGROUND & AIMS: There is much interest in wheat sensitivity among people without celiac disease (CD), but little is known about any risks associated with the condition. We evaluated the prevalence of autoimmune diseases (ADs) among patients with nonceliac wheat sensitivity (NCWS), and investigated whether they carry antinuclear antibodies (ANA). METHODS: We performed a retrospective study of 131 patients diagnosed with NCWS (121 female; mean age, 29.1 years) at 2 hospitals in Italy from January 2001 through June 2011. Data were also collected from 151 patients with CD or irritable bowel syndrome (IBS) (controls). Patient medical records were reviewed to identify those with ADs. We also performed a prospective study of 42 patients (38 female; mean age, 34 years) diagnosed with NCWS from July 2011 through March 2014 at 3 hospitals in Italy. One hundred age- and sex-matched subjects with CD or IBS served as controls. Serum samples were collected from all subjects and ANA levels were measured by immunofluorescence analysis. Participants completed a questionnaire and their medical records were reviewed to identify those with ADs. RESULTS: In the retrospective analysis, similar portions of subjects with NCWS (29%) and CD (29%) developed ADs (mainly Hashimoto's thyroiditis, 29 cases), compared with a smaller proportion of subjects with IBS (4%) (P < .001). In the prospective study, 24% of subjects with NCWS, 20% of subjects with CD, and 2% of subjects with IBS developed ADs (P < .001). In the retrospective study, serum samples tested positive for ANA in 46% of subjects with NCWS (median titer, 1:80), 24% of subjects with CD (P < .001), and 2% of subjects IBS (P < .001); in the prospective study, serum samples were positive for ANA in 28% of subjects with NCWS, 7.5% of subjects with CD (P = .02), and 6% of subjects with IBS (P = .005 vs patients with NCWS). ANA positivity was associated with the presence of the HLA DQ2/DQ8 haplotypes (P < .001). CONCLUSIONS: Higher proportions of patients with NCWS or CD develop autoimmune disorders, are ANA positive, and showed DQ2/DQ8 haplotypes compared with patients with IBS.

Role of FODMAPs in Patients With Irritable Bowel Syndrome.

Irritable bowel syndrome (IBS) is a condition characterized by abdominal pain, bloating, flatus, and altered bowel habits. The role of dietary components in inducing IBS symptoms is difficult to explore. To date, foods are not considered a cause but rather symptom-triggering factors. Particular interest has been given to the so-called FODMAPs (fermentable oligo-, di-, and monosaccharides and polyols). We aimed to summarize the evidence from the most common approaches to manage suspected food intolerance in IBS, with a particular interest in the role of FODMAPs and the effects of a low FODMAP diet. We reviewed literature, consulting PubMed and Medline by using the search terms FODMAP(s), fructose, lactose, fructans, galactans, polyols (sorbitol, mannitol, maltitol, xylitol, erythritol, polydextrose, and isomalt), irritable bowel syndrome, and functional gastrointestinal symptoms. FODMAP-restricted diets have been used for a long time to manage patients with IBS. The innovation in the so-called FODMAP concept is that a global restriction should have a more consistent effect than a limited one in preventing abdominal distension. Even though all the potential low FODMAP diets provide good relief of symptoms in many patients, there is just a little relief in others. Several studies highlight the role of low FODMAP diets to improve symptoms in patients with IBS. The evidence on this dietary approach supports the hypothesis that a low FODMAP diet should be the first dietary approach. However, many points remain to be clarified, including the evaluation of possibly significant nutrition concerns.

Risk of low bone mineral density and low body mass index in patients with non-celiac wheat-sensitivity: a prospective observation study.

BACKGROUND: Non-celiac gluten sensitivity (NCGS) or 'wheat sensitivity' (NCWS) is included in the spectrum of gluten-related disorders. No data are available on the prevalence of low bone mass density (BMD) in NCWS. Our study aims to evaluate the prevalence of low BMD in NCWS patients and search for correlations with other clinical characteristics. METHODS: This prospective observation study included 75 NCWS patients (63 women; median age 36 years) with irritable bowel syndrome (IBS)-like symptoms, 65 IBS and 50 celiac controls. Patients were recruited at two Internal Medicine Departments. Elimination diet and double-blind placebo controlled (DBPC) wheat challenge proved the NCWS diagnosis. All subjects underwent BMD assessment by Dual Energy X-Ray Absorptiometry (DXA), duodenal histology, HLA DQ typing, body mass index (BMI) evaluation and assessment for daily calcium intake. RESULTS: DBPC cow's milk proteins challenge showed that 30 of the 75 NCWS patients suffered from multiple food sensitivity. Osteopenia and osteoporosis frequency increased from IBS to NCWS and to celiac disease (CD) (P <0.0001). Thirty-five NCWS patients (46.6%) showed osteopenia or osteoporosis. Low BMD was related to low BMI and multiple food sensitivity. Values of daily dietary calcium intake in NCWS patients were significantly lower than in IBS controls. CONCLUSIONS: An elevated frequency of bone mass loss in NCWS patients was found; this was related to low BMI and was more frequent in patients with NCWS associated with other food sensitivity. A low daily intake of dietary calcium was observed in patients with NCWS.

Non-celiac gluten sensitivity: literature review.

BACKGROUND: A significant percentage of the general population report problems caused by wheat and/or gluten ingestion, even though they do not have celiac disease (CD) or wheat allergy (WA), because they test negative both for CD-specific serology and histopathology and for immunoglobulin E (IgE)-mediated assays. Most patients report both gastrointestinal and nongastrointestinal symptoms, and all report improvement of symptoms on a gluten-free diet. This clinical condition has been named non-celiac gluten sensitivity (NCGS). AIM: We attempt to define the current pathogenic, clinical, and diagnostic criteria of this "new" disease, to provide a practical view that might be useful to evaluate, diagnose, and manage NCGS patients. METHODS: We reviewed the international literature through PubMed and Medline, using the search terms "wheat (hyper)sensitivity," "wheat allergy," "wheat intolerance," "gluten (hyper)sensitivity," and "gluten intolerance," and we discuss current knowledge about NCGS. RESULTS: It has been demonstrated that patients suffering from NCGS are a heterogeneous group, composed of several subgroups, each characterized by different pathogenesis, clinical history, and, probably, clinical course. NCGS diagnosis can be reached only by excluding CD and WA. Recent evidence shows that a personal history of food allergy in infancy, coexistent atopy, positive for immunoglobulin G (IgG) antigliadin antibodies and flow cytometric basophil activation test, with wheat and duodenal and/or ileum-colon intraepithelial and lamina propria eosinophil counts, could be useful to identify NCGS patients. CONCLUSIONS: Future research should aim to identify reliable biomarkers for NCGS diagnosis and to better define the different NCGS subgroups. Key teaching points: • Most patients report both gastrointestinal and nongastrointestinal symptoms, and all agree that there is an improvement of symptoms on a gluten-free diet. • NCGS diagnosis can be reached only by excluding celiac disease and wheat allergy. • Patients suffering from NCGS are a heterogeneous group, composed of several subgroups, each characterized by different pathogenesis, clinical history, and, probably, clinical course. • A personal history of food allergy in infancy, coexistent atopy, positive IgG antigliadin antibodies (AGA) and flow cytometric basophil activation test, with wheat and duodenal and/or ileum-colon intraepithelial and lamina propria eosinophil counts, could be useful to identify NCGS patients. • Future research should aim to identify reliable biomarkers for NCGS diagnosis and to better define the different NCGS subgroup.