Prevalence of Wheat/Gluten-Related Disorders and Gluten-Free Diet in Paraguay: An Online Survey-Based Study.

Gluten-related disorders (GRDs) are increasing around the world, but their magnitude and relevance remain unknown in most Latin American countries. Thus, an online survey was conducted to estimate the prevalence of GRDs as well as adherence to a gluten-free diet (GFD) in Paraguayan adult population. There were 1058 individuals surveyed using a validated questionnaire (response rate of 93.9%). The self-reported prevalence rates were as follows (95% CI): gluten sensitivity (GS), 10.30% (8.53-12.29); non-celiac GS (NCGS), 5.19% (3.94-6.71); physician-diagnosed celiac disease (PD-CD), 3.11% (2.15-4.35); wheat allergy (WA), 2.07% (1.30-3.13); and adherence to GFD, 15.69% (13.55-18.02). Excluding CD, more women than men met the criteria for GRDs, adverse food reactions, and GFD (p < 0.05). Eight respondents reported the coexistence of NCGS with PD-CD and/or WA. Most cases on a GFD indicated medical/dietitian advice for following the diet (68.07%). Non-self-reported GS individuals indicated weight control (46.4%) and the notion that the GFD is healthier (20.2%) as the main motivations for following the diet. GRDs are not uncommon in Paraguayan adult population. It seems that there is awareness about GRDs and the GFD, but training about the diagnosis of GRDs is desirable because of the informed overlapping diagnoses of CD or WA with NCGS. Future studies involving face-to-face interviews are necessary.

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.

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.

Effect of Gluten-Free Diet on Gut Microbiota Composition in Patients with Celiac Disease and Non-Celiac Gluten/Wheat Sensitivity.

Celiac disease (CD) and non-celiac gluten/wheat sensitivity (NCG/WS) are the two most frequent conditions belonging to gluten-related disorders (GRDs). Both these diseases are triggered and worsened by gluten proteins ingestion, although other components, such as amylase/trypsin inhibitors (ATI) and fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs), seem to be involved in the NCG/WS onset. Therefore, the only effective treatment to date is the long-life adherence to a strictly gluten-free diet. Recently, increasing attention has been paid to the intestinal barrier, a dynamic system comprising various components, which regulate the delicate crosstalk between metabolic, motor, neuroendocrine and immunological functions. Among the elements characterizing the intestinal barrier, the microbiota plays a key role, modulating the gut integrity maintenance, the immune response and the inflammation process, linked to the CD and NCG/WS outbreak. This narrative review addresses the most recent findings on the gut microbiota modulation induced by the gluten-free diet (GFD) in healthy, CD and NCG/WS patients.

Noncoeliac wheat sensitivity and diet.

PURPOSE OF REVIEW: Noncoeliac gluten sensitivity (NCGS) can be suspected after exclusion of coeliac disease and wheat allergy. However, poorly understood pathogenesis of the NCGS, lack of gold standard for diagnosis and agreement in the definition for the NCGS condition, open the space for future investigation. This review aims to give an overview on the diagnosis and effective diet composition in the treatment of NCGS symptoms. RECENT FINDINGS: It appears that a diet low in fermentable oligo, di, and monosaccharides and polyols (FODMAPs) and gluten-free diet play a prominent role in the strategy of NCGS management. Considering available evidence with respect to diagnostic tools, it is challenging to prepare a standard guideline for NCGS diagnosis and treatment with clear cut-offs for symptom reduction/improvement that could directly be translated into test results. Nutritional support, including the use of pre/probiotics, has to be tailored to the individual situation of NCGS patients. SUMMARY: The exclusion of such components of wheat as amylase/trypsin inhibitors, wheat-germ agglutinins, or free of FODMAPs diet can reduce clinical symptoms of NCGS. The further investigation on microbiota changes may strengthen the knowledge in this area, where the major challenge is to develop biomarkers for NCGS investigation.

Clinical and in vitro cross-reactivity of cereal grains in children with IgE-mediated wheat allergy.

INTRODUCTION AND OBJECTIVES: Wheat and cereal grains have a broad range of cross-reactivity, but the clinical relevance of this cross-reactivity is uncertain. This study aimed to evaluate clinical and in vitro cross-reactivity with barley, oat, and Job's tears among wheat-allergic patients. MATERIALS AND METHODS: Patients aged 5 to 15 years with IgE-mediated wheat allergy were enrolled. Skin prick test (SPT) and specific IgE (sIgE) to wheat, barley, and oat, and SPT to Job's tears were performed. Oral food challenge (OFC) was conducted if the SPT was ≤5 mm in size and there was no history of anaphylaxis to each grain. Profiles of sIgE bound allergens of wheat, barley, and oat, and inhibition ELISA of IgE binding to barley and oat with wheat were performed. RESULTS: Ten patients with a median age of 8 years were enrolled. Nine of those patients had a history of wheat anaphylaxis. The median SPT size and sIgE level to wheat was 7.3 mm and 146.5 kUA/l, respectively. The cross-reactivity rate for barley, oat, and Job's tears was 60.0%, 33.3%, and 20.0%, respectively. Significantly larger SPT size and higher sIgE level were observed in patients with positive cross-reactivity to barley and oat when compared to patients without cross-reactivity. Barley and oat extracts inhibited 59% and 16% of sIgE bound to wheat gliadins and glutenins, respectively. CONCLUSION: The cross-reactivity rate was quite low for oat and Job's tears compared to that of barley; therefore, avoidance of all cereal grains may be unnecessary in patients with severe wheat allergy.

Incidence and prevalence of self-reported non-coeliac wheat sensitivity and gluten avoidance in Australia.

OBJECTIVES: To determine the incidence of self-reported non-coeliac wheat sensitivity (SR-NCWS) and factors associated with its onset and resolution; to describe the prevalence of factors associated with gluten avoidance. DESIGN: Longitudinal cohort study; analysis of responses to self-administered validated questionnaires (Digestive Health and Wellbeing surveys, 2015 and 2018). SETTING, PARTICIPANTS: Subset of an adult population sample randomly selected in 2015 from the electoral rolls for the Newcastle and Gosford regions of New South Wales. MAIN OUTCOME MEASURES: Prevalence of SR-NCWS (2015, 2018) and incidence and resolution of SR-NCWS, each by demographic and medical factors; prevalence of gluten avoidance and reasons for gluten avoidance (2018). RESULTS: 1322 of 2185 eligible participants completed the 2018 survey (response rate, 60.5%). The prevalence of SR-NCWS was similar in 2015 (13.8%; 95% CI, 12.0-15.8%) and 2018 (13.9%; 95% CI, 12.1-15.9%); 69 of 1301 respondents (5.3%) reported developing new onset (incident) SR-NCWS between 2015 and 2018 (incidence, 1.8% per year). Incident SR-NCWS was significantly associated with a diagnosis of functional dyspepsia, and negatively associated with being male or older. Gluten avoidance was reported in 2018 by 24.2% of respondents (20.5% partial, 3.8% complete avoidance); general health was the most frequent reason for avoidance (168 of 316 avoiders, 53%). All 13 participants with coeliac disease, 56 of 138 with irritable bowel syndrome (41%), and 69 of 237 with functional dyspepsia (29%) avoided dietary gluten. CONCLUSIONS: The prevalence of SR-NCWS was similar in 2015 and 2018. Baseline (2015) and incident SR-NCWS (2018) were each associated with functional gastrointestinal disorders. The number of people avoiding dietary gluten exceeds that of people with coeliac disease or SR-NCWS, and general health considerations and abdominal symptoms are the most frequently reported reasons for avoidance.

Going Against the Grains: Gluten-Free Diets in Patients Without Celiac Disease-Worthwhile or Not?

While the gluten-free diet (GFD) is the only known effective therapy for celiac disease, in recent years it has become increasingly popular in the USA and worldwide, with many believing it to be more "healthful" and others claiming that it has beneficial effects for health conditions, many extraintestinal, other than celiac disease. This review examines the evidence for use of the GFD in patients without celiac disease who self-report intestinal and/or extraintestinal symptoms (non-celiac gluten sensitivity), as well as for enhancement of athletic performance and treatment of autism, rheumatoid arthritis, and psychiatric disorders. Overall, the evidence for use of GFDs in conditions other than celiac disease is poor. Though non-celiac gluten sensitivity may ultimately emerge as a biomarker-defined condition, a large proportion of patients with apparent non-celiac gluten sensitivity have, after careful investigation, an alternative diagnosis. In light of this, and coupled with the potential physical and psychological harms associated with the avoidance of gluten, initiating a GFD should not be encouraged for people who have these other conditions or are seeking physical/athletic enhancement.

The overlap of irritable bowel syndrome and noncoeliac gluten sensitivity.

PURPOSE OF REVIEW: There has been significant interest in gluten over the last decade, with an increase in interest of gluten-related disorders outside coeliac disease. Particularly, there has been a focus on the role of gluten in noncoeliac gluten sensitivity (NCGS) and irritable bowel syndrome (IBS). There is significant overlap between both of these conditions, with the aim of this review to explore their complex relationship. RECENT FINDINGS: Gluten has been demonstrated to generate symptoms in individuals with NCGS. However, there appears to be an increasing role for gluten in symptom generation in patients with IBS also. Other components of wheat, other than gluten, are now also thought to be contributing factors in symptom generation. SUMMARY: There appears to be significant overlap between IBS and NCGS. It is likely that a subset of patients presenting with IBS actually have NCGS. In addition, it is likely that individuals with IBS may also have symptoms triggered by gluten. With the pathophysiology of both conditions not fully understood, as well as increasing knowledge of wheat components in symptom generation, further research is required to help distinguish between both.

Who Should Be Gluten-Free? A Review for the General Practitioner.

Historically, a gluten-free diet was recommended only for those with celiac disease or IgE-mediated wheat allergy. With changes in food allergy labeling in the United States and the publication of several best-selling books, gluten-related disorders have come to the forefront of popular culture. As a result, there has been a dramatic increase in the number of gluten-free diet followers, many for nontraditional reasons. As "going gluten-free" has become mainstream, it is imperative that health care providers acquire the knowledge to identify true gluten-related disorders to effectively counsel their patients and minimize potential complications from following such a restrictive diet.

Long term effects of gluten-free diet in non-celiac wheat sensitivity.

BACKGROUND & AIMS: Information about the clinical outcome of patients with non-celiac wheat sensitivity (NCWS) treated with gluten-free diet (GFD) derive from studies assessing the symptom response in the first few weeks of treatment. We aimed to evaluate the clinical response to the GFD and the quality of life (QoL) of NCWS patients in the long term. METHODS: Forty-four NCWS (diagnosed according to the Salerno criteria) participated in the study. Participants rated their symptoms according to a 0-10 scale patients and filled in a QoL questionnaire (CDQ) before the beginning of the GFD and during a follow-up evaluation performed after at least one year. To assess the reliability of the questionnaire we also included a control group of 43 matched patients with celiac disease (CD). RESULTS: Upon diagnosis, NCWS patients had a high prevalence of intestinal and extraintestinal symptoms. Also, most symptoms were described as severe and the QoL questionnaire showed high scores. On follow-up, both prevalence and severity of the most common symptoms were significantly reduced. However, persistent intestinal and extraintestinal symptoms of mild severity were found in 65.9 and 72.7% of NCWS patients. In comparison, in the CD group, the prevalence was lower (32.6 and 23.2% respectively) and consistent with previous studies. The analyses of the determinant of QoL showed that, upon diagnosis, NCWS patients had higher scores in the CDQ "gastrointestinal symptoms" (p < 0.001), "emotional aspects" (p < 0.001) and "social problems" (p < 0.001) subclasses compared to CD patients. After the GFD, NCWS and CD patients shared similar scores in all of the subclasses. CONCLUSIONS: A significant proportion of NCWS patients still complains of intestinal and extraintestinal symptoms, even if significantly attenuated by the GFD, even years after the diagnosis. A comprehensive nutritional evaluation of these patients is required to further improve their symptoms and their QoL.

Breve revisión sobre controversias en la sensibilidad al gluten / trigo no celíaca. Respuestas prácticas a preguntas frecuentes / No disponible

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Non-celiac gluten sensitivity: where are we now?

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Marco socioantropológico de la enfermedad celíaca y sensibilidad al gluten; presente y futuro / No disponible

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Movement Disorders Related to Gluten Sensitivity: A Systematic Review.

Gluten related disorders (GRD) represent a wide spectrum of clinical manifestations that are triggered by the ingestion of gluten. Coeliac disease (CD) or gluten sensitive enteropathy is the most widely recognised, but extra-intestinal manifestations have also been increasingly identified and reported. Such manifestations may exist in the absence of enteropathy. Gluten sensitivity (GS) is another term that has been used to include all GRD, including those where there is serological positivity for GS related antibodies in the absence of an enteropathy. Gluten ataxia (GA) is the commonest extraintestinal neurological manifestation and it has been the subject of many publications. Other movement disorders (MDs) have also been reported in the context of GS. The aim of this review was to assess the current available medical literature concerning MDs and GS with and without enteropathy. A systematic search was performed while using PubMed database. A total of 48 articles met the inclusion criteria and were included in the present review. This review highlights that the phenomenology of gluten related MDs is broader than GA and demonstrates that gluten-free diet (GFD) is beneficial in a great percentage of such cases.

Psychiatric Comorbidity in Children and Adults with Gluten-Related Disorders: A Narrative Review.

Gluten-related disorders are characterized by both intestinal and extraintestinal manifestations. Previous studies have suggested an association between gluten-related disorder and psychiatric comorbidities. The objective of our current review is to provide a comprehensive review of this association in children and adults. A systematic literature search using MEDLINE, Embase and PsycINFO from inception to 2018 using terms of ‘celiac disease’ or ‘gluten-sensitivity-related disorders’ combined with terms of ‘mental disorders’ was conducted. A total of 47 articles were included in our review, of which 28 studies were conducted in adults, 11 studies in children and eight studies included both children and adults. The majority of studies were conducted in celiac disease, two studies in non-celiac gluten sensitivity and none in wheat allergy. Enough evidence is currently available supporting the association of celiac disease with depression and, to a lesser extent, with eating disorders. Further investigation is warranted to evaluate the association suggested with other psychiatric disorders. In conclusion, routine surveillance of potential psychiatric manifestations in children and adults with gluten-related disorders should be carried out by the attending physician.

Non-Celiac Gluten Sensitivity: How Its Gut Immune Activation and Potential Dietary Management Differ from Celiac Disease.

Non-celiac gluten sensitivity (NCGS) is a clinical entity triggered by the ingestion of gluten-containing grains leading to intestinal and/or extraintestinal symptoms that resolve once the gluten-containing foodstuff is eliminated from the diet, and it is diagnosed when celiac disease (CD) and wheat allergy (WA) have been ruled out. The limited knowledge about the pathophysiology of NCGS and the lack of validated biomarkers are still major limitations for clinical studies, making it difficult to differentiate NCGS from other gluten-related disorders (GRD). In the absence of clear-cut diagnostic criteria, NCGS is still mainly a diagnosis of exclusion. Several studies suggest that NCGS is an immune-mediated disease that likely activates an innate immune response. Moreover, it has recently been hypothesized that in addition to gluten, other components of wheat may be responsible for the symptoms observed in individuals without CD. This review aims at discussing available evidence related to the histological and immunological features in the gut mucosa of patients with NCGS and at outlining new dietary opportunities for these patients.

Fructan, Rather Than Gluten, Induces Symptoms in Patients With Self-Reported Non-Celiac Gluten Sensitivity.

BACKGROUND & AIMS: Non-celiac gluten sensitivity is characterized by symptom improvement after gluten withdrawal in absence of celiac disease. The mechanisms of non-celiac gluten sensitivity are unclear, and there are no biomarkers for this disorder. Foods with gluten often contain fructans, a type of fermentable oligo-, di-, monosaccharides and polyols. We aimed to investigate the effect of gluten and fructans separately in individuals with self-reported gluten sensitivity. METHODS: We performed a double-blind crossover challenge of 59 individuals on a self-instituted gluten-free diet, for whom celiac disease had been excluded. The study was performed at Oslo University Hospital in Norway from October 2014 through May 2016. Participants were randomly assigned to groups placed on diets containing gluten (5.7 g), fructans (2.1 g), or placebo, concealed in muesli bars, for 7 days. Following a minimum 7-day washout period (until the symptoms induced by the previous challenge were resolved), participants crossed over into a different group, until they completed all 3 challenges (gluten, fructan, and placebo). Symptoms were measured by Gastrointestinal Symptom Rating Scale Irritable Bowel Syndrome (GSRS-IBS) version. A linear mixed model for analysis was used. RESULTS: Overall GSRS-IBS scores differed significantly during gluten, fructan, and placebo challenges; mean values were 33.1 ± 13.3, 38.6 ± 12.3, and 34.3 ± 13.9, respectively (P = .04). Mean scores for GSRS-IBS bloating were 9.3 ± 3.5, 11.6 ± 3.5, and 10.1 ± 3.7, respectively, during the gluten, fructan, and placebo challenges (P = .004). The overall GSRS-IBS score for participants consuming fructans was significantly higher than for participants consuming gluten (P = .049), as was the GSRS bloating score (P = .003). Thirteen participants had the highest overall GSRS-IBS score after consuming gluten, 24 had the highest score after consuming fructan, and 22 had the highest score after consuming placebo. There was no difference in GSRS-IBS scores between gluten and placebo groups. CONCLUSIONS: In a randomized, double-blind, placebo-controlled crossover study of individuals with self-reported non-celiac gluten sensitivity, we found fructans to induce symptoms, measured by the GSRS-IBS. Clinicaltrials.gov no: NCT02464150.