SciCombinator

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Concept: Wheat gluten

169

Non-celiac gluten sensitivity is a syndrome characterized by gastrointestinal and extra-intestinal symptoms occurring in a few hours/days after gluten and/or other wheat protein ingestion and rapidly improving after exclusion of potential dietary triggers. There are no established laboratory markers for non-celiac gluten sensitivity, although a high prevalence of first generation anti-gliadin antibodies of IgG class has been reported in this condition. This study was designed to characterize the effect of the gluten-free diet on anti-gliadin antibodies of IgG class in patients with non-celiac gluten sensitivity.

Concepts: Immune system, Wheat, Coeliac disease, Gluten, Gluten-free diet, Dermatitis herpetiformis, Rice, Wheat gluten

117

Gluten-free diet (GFD) is the only management for coeliac disease (CD). Available methods to assess GFD compliance are insufficiently sensitive to detect occasional dietary transgressions that may cause gut mucosal damage. We aimed to develop a method to determine gluten intake and monitor GFD compliance in patients with CD and to evaluate its correlation with mucosal damage.

Concepts: Death, Wheat, Coeliac disease, Gluten, Gluten-free diet, Dermatitis herpetiformis, Wheat gluten, Gliadin

30

Adherence to a gluten-free diet (GFD) for non-coeliac athletes (NCA) has become increasingly popular despite a paucity of supportive medical or ergogenic evidence. This study aimed to quantify the demographics of NCA and determine associated experiences, perceptions and sources of information related a GFD. Athletes (n=910, female=528, no gender selected=5) completed a 17-question online survey. Forty-one percent of NCA respondents, including 18-world and/or Olympic medalists, follow a GFD 50%-100% of the time (GFD>50): only 13% for treatment of reported medical conditions with 57% self-diagnosing their gluten sensitivity. The GFD>50 group characteristics included predominantly endurance sport athletes (70.0%) at the recreationally competitive level (32.3%), between 31-40 years of age (29.1%). Those who follow a GFD>50 reported experiencing, abdominal/gastrointestinal (GI) symptoms alone (16.7%) or in conjunction with two (30.7%) or three (35.7%) additional symptoms (e.g. fatigue) believed to be triggered by gluten. Eighty-four percent of GFD>50 indicted symptom improvement with gluten-removal. Symptom-based and non-symptom-based self-diagnosed gluten-sensitivity (56.7%) was the primary reason for adopting a GFD. Leading sources of GFD information were: online (28.7%), trainer/coach (26.2%) and other athletes (17.4%). Although 5-10% of the general population is estimated to benefit clinically from a GFD a higher prevalence of GFD adherence was found in NCA (41.2%). Prescription of a GFD amongst many athletes does not result from evidence-based practice suggesting that adoption of a GFD in the majority of cases was not based on medical rationale and may be driven by perception that gluten removal provides health benefits and an ergogenic edge in NCA.

Concepts: Disease, Symptom, Wheat, Coeliac disease, Gluten, Gluten-free diet, Dermatitis herpetiformis, Wheat gluten

21

Non-celiac gluten sensitivity (NCGS) is characterized by the onset of symptoms after eating gluten-containing food. We aimed to single out NCGS subjects among subjects with functional gastrointestinal symptoms. Patients were enrolled in a multicenter double-blind placebo-controlled trial with crossover. Symptoms and quality of life were evaluated by means of 10-cm VAS and SF36. Iron parameters, transaminases and C reactive protein (CRP) were evaluated. After a three-week-long gluten-free diet (GFD), responsive patients were randomly assigned to gluten intake (5.6 g/day) or placebo for seven days, followed by crossover. The primary endpoint was the worsening of symptoms (VAS increase ≥3 cm) during gluten ingestion compared to placebo. One hundred and forty patients were enrolled and 134 (17 males, mean age 39.1 ± 11.7 years, BMI 22.4 ± 3.8) completed the first period. A total of 101 subjects (10 males, mean age 39.3 ± 11.0 years, BMI 22.3 ± 4.0) reported a symptomatic improvement (VAS score 2.3 ± 1.2 vs. 6.5 ± 2.2 before and after GFD, p = 0.001). 98 patients underwent the gluten challenge and 28 (all females, mean age 38.9 ± 12.7 years, BMI 22.0 ± 2.9) reported a symptomatic relapse and deterioration of quality of life. No parameters were found to be statistically associated with positivity to the challenge. However, 14 patients responded to the placebo ingestion. Taking into account this finding, about 14% of patients responding to gluten withdrawal showed a symptomatic relapse during the gluten challenge. This group is suspected to have NCGS.

Concepts: Wheat, Randomness, C-reactive protein, Coeliac disease, Gluten, Gluten-free diet, Dermatitis herpetiformis, Wheat gluten

11

Treatment of coeliac disease requires a strict gluten-free (GF) diet, however, a high proportion of patients do not adhere to a GF diet. The study explores the practical challenges of a GF diet and dietary adherence in Caucasian and South Asian adults with coeliac disease. Patients with biopsy- and serology-proven coeliac disease were recruited from a hospital database. Participants completed a postal survey (n = 375), including a validated questionnaire designed to measure GF dietary adherence. Half of Caucasians (53%) and South Asians (53%) were adhering to a GF diet. The quarter of patients (n = 97) not receiving GF foods on prescription had a lower GF dietary adherence score compared with those receiving GF foods on prescription (12.5 versus 16.0; p < 0.001). Not understanding food labelling and non-membership of Coeliac UK were also associated with lower GF dietary adherence scores. A higher proportion of South Asian patients, compared with Caucasians, reported difficulties understanding what they can eat (76% versus 5%; p < 0.001) and understanding of food labels (53% versus 4%; p < 0.001). We recommend retaining GF foods on prescription, membership of a coeliac society, and regular consultations with a dietitian to enable better understanding of food labels. Robust studies are urgently needed to evaluate the impact of reducing the amount of GF foods prescribed on adherence to a GF diet in all population groups.

Concepts: Nutrition, Wheat, Coeliac disease, Gluten, Gluten-free diet, Dermatitis herpetiformis, Rice, Wheat gluten

10

Celiac disease is an autoimmune enteropathy caused by gluten in genetically predisposed individuals. In celiac disease, adaptive and innate immune activation results in intestinal damage and a wide range of clinical manifestations. In the past, celiac disease was thought to result in signs and symptoms solely related to the gastrointestinal tract. Now, more than half of the adult population presents with extra-intestinal manifestations that can also be expected to improve on a gluten-free diet. For this reason, it is recommended that physicians have a low threshold of suspicion for celiac disease. Current knowledge of the immune pathogenesis of this autoimmune disease has served as a catalyst for the development of novel diagnostic tools and therapeutics. Over the years, highly sensitive and specific serological assays, in addition to genetic markers, have been found to target specific steps in the cascade pathway of celiac disease. Also the advent of the gluten challenge has enabled experts to design diagnostic algorithms and monitor clinical responses in clinical trials. The gluten challenge has provided substantial benefit in the advance of novel therapeutics as an adjuvant treatment to the gluten free diet. Generally, a strict gluten-free diet is highly burdensome to patients and can be limited in its efficacy. Alternative therapies-including gluten modification, modulation of intestinal permeability and immune response-could be central to the future treatment of celiac disease.

Concepts: Immune system, Wheat, Coeliac disease, Gluten, Gluten-free diet, Dermatitis herpetiformis, Rice, Wheat gluten

7

A gluten-free diet is the only means to manage coeliac disease, a permanent immune intolerance to gluten. We developed a therapeutic vaccine, Nexvax2, designed to treat coeliac disease. Nexvax2 is an adjuvant-free mix of three peptides that include immunodominant epitopes for gluten-specific CD4-positive T cells. The vaccine is intended to engage and render gluten-specific CD4-positive T cells unresponsive to further antigenic stimulation. We assessed the safety and pharmacodynamics of the vaccine in patients with coeliac disease on a gluten-free diet.

Concepts: Immune system, Protein, Wheat, Coeliac disease, Gluten, Gluten-free diet, Dermatitis herpetiformis, Wheat gluten

6

Celiac disease (CD) is an autoimmune-mediated enteropathy triggered by dietary gluten in genetically prone individuals. The current treatment for CD is a strict lifelong gluten-free diet. However, in some CD patients following a strict gluten-free diet, the symptoms do not remit. These cases may be refractory CD or due to gluten contamination; however, the lack of response could be related to other dietary ingredients, such as maize, which is one of the most common alternatives to wheat used in the gluten-free diet. In some CD patients, as a rare event, peptides from maize prolamins could induce a celiac-like immune response by similar or alternative pathogenic mechanisms to those used by wheat gluten peptides. This is supported by several shared features between wheat and maize prolamins and by some experimental results. Given that gluten peptides induce an immune response of the intestinal mucosa both in vivo and in vitro, peptides from maize prolamins could also be tested to determine whether they also induce a cellular immune response. Hypothetically, maize prolamins could be harmful for a very limited subgroup of CD patients, especially those that are non-responsive, and if it is confirmed, they should follow, in addition to a gluten-free, a maize-free diet.

Concepts: Immune system, Humoral immunity, Wheat, Coeliac disease, Gluten, Gluten-free diet, Rice, Wheat gluten

4

Gluten-free diet (GFD) is the only treatment for celiac disease (CD). There is a general consensus that strict GFD adherence in CD patients leads to full clinical and histological remission accompanied by improvement in quality of life and reduced long-term complications. Despite the importance of monitoring the GFD, there are no clear guidelines for assessing the outcome or for exploring its adherence. Available methods are insufficiently accurate to identify occasional gluten exposure that may cause intestinal mucosal damage. Serological tests are highly sensitive and specific for diagnosis, but do not predict recovery and are not useful for follow-up. The use of serial endoscopies, it is invasive and impractical for frequent monitoring, and dietary interview can be subjective. Therefore, the detection of gluten immunogenic peptides (GIP) in feces and urine have been proposed as new non-invasive biomarkers to detect gluten intake and verify GFD compliance in CD patients. These simple immunoassays in human samples could overcome some key unresolved scientific and clinical problems in CD management. It is a significant advance that opens up new possibilities for the clinicians to evaluate the CD treatment, GFD compliance, and improvement in the quality of life of CD patients.

Concepts: Medical terms, Wheat, Coeliac disease, Gluten, Gluten-free diet, Dermatitis herpetiformis, Rice, Wheat gluten

4

Several studies have shown that a large number of patients who are fulfilling the criteria for irritable bowel syndrome (IBS) are sensitive to gluten. The aim of this study was to evaluate the effect of a gluten-free diet on gastrointestinal symptoms in patients with IBS. In this double-blind randomized, placebo-controlled trial, 148 IBS patients fulfilling the Rome III criteria were enrolled between 2011 and 2013. However, only 72 out of the 148 commenced on a gluten-free diet for up to six weeks and completed the study; clinical symptoms were recorded biweekly using a standard visual analogue scale (VAS). In the second stage after six weeks, patients whose symptoms improved to an acceptable level were randomly divided into two groups; patients either received packages containing powdered gluten (35 cases) or patients received placebo (gluten free powder) (37 cases). Overall, the symptomatic improvement was statistically different in the gluten-containing group compared with placebo group in 9 (25.7%), and 31 (83.8%) patients respectively (p < 0.001). A large number of patients labelled as irritable bowel syndrome are sensitive to gluten. Using the term of IBS can therefore be misleading and may deviate and postpone the application of an effective and well-targeted treatment strategy in gluten sensitive patients.

Concepts: Wheat, Placebo, Irritable bowel syndrome, Coeliac disease, Gluten, Gluten-free diet, Dermatitis herpetiformis, Wheat gluten