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Concept: Gluten-free diet

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Gluten exclusion (protein complex present in many cereals) has been proposed as an option for the prevention of diseases other than coeliac disease. However, the effects of gluten-free diets on obesity and its mechanisms of action have not been studied. Thus, our objective was to assess whether gluten exclusion can prevent adipose tissue expansion and its consequences. C57BL/6 mice were fed a high-fat diet containing 4.5% gluten (Control) or no gluten (GF). Body weight and adiposity gains, leukocyte rolling and adhesion, macrophage infiltration and cytokine production in adipose tissue were assessed. Blood lipid profiles, glycaemia, insulin resistance and adipokines were measured. Expression of the PPAR-α and γ, lipoprotein lipase (LPL), hormone sensitive lipase (HSL), carnitine palmitoyl acyltransferase-1 (CPT-1), insulin receptor, GLUT-4 and adipokines were assessed in epidydimal fat. Gluten-free animals showed a reduction in body weight gain and adiposity, without changes in food intake or lipid excretion. These results were associated with up-regulation of PPAR-α, LPL, HSL and CPT-1, which are related to lipolysis and fatty acid oxidation. There was an improvement in glucose homeostasis and pro-inflammatory profile-related overexpression of PPAR-γ. Moreover, intravital microscopy showed a lower number of adhered cells in the adipose tissue microvasculature. The overexpression of PPAR-γ is related to the increase of adiponectin and GLUT-4. Our data support the beneficial effects of gluten-free diets in reducing adiposity gain, inflammation and insulin resistance. The data suggests that diet gluten exclusion should be tested as a new dietary approach to prevent the development of obesity and metabolic disorders.

Concepts: Protein, Metabolism, Nutrition, Obesity, Fat, Insulin resistance, Adipose tissue, Gluten-free diet

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A gluten-free diet (GFD) is the most commonly adopted special diet worldwide. It is an effective treatment for coeliac disease and is also often followed by individuals to alleviate gastrointestinal complaints. It is known there is an important link between diet and the gut microbiome, but it is largely unknown how a switch to a GFD affects the human gut microbiome.

Concepts: Gut flora, Wheat, Gastroenterology, Coeliac disease, Gluten, Gluten-free diet, Dermatitis herpetiformis, Diets

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Celiac disease is a multisystem immune based disorder that is triggered by the ingestion of gluten in genetically susceptible individuals. The prevalence of celiac disease has risen in recent decades and is currently about 1% in most Western populations. The reason for this rise is unknown, although environmental factors related to the hygiene hypothesis are suspected. The pathophysiology of celiac disease involves both the innate and adaptive immune response to dietary gluten. Clinical features are diverse and include gastrointestinal symptoms, metabolic bone disease, infertility, and many other manifestations. Although a gluten-free diet is effective in most patients, this diet can be burdensome and can limit quality of life; consequently, non-dietary therapies are at various stages of development. This review also covers non-celiac gluten sensitivity. The pathophysiology of this clinical phenotype is poorly understood, but it is a cause of increasing interest in gluten-free diets in the general population.

Concepts: Immune system, Nutrition, Death, Wheat, Coeliac disease, Gluten, Gluten-free diet, Dermatitis herpetiformis

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Fibromyalgia (FM) syndrome is a disabling clinical condition of unknown cause, and only symptomatic treatment with limited benefit is available. Gluten sensitivity that does not fulfill the diagnostic criteria for celiac disease (CD) is increasingly recognized as a frequent and treatable condition with a wide spectrum of manifestations that overlap with the manifestations of FM, including chronic musculoskeletal pain, asthenia, and irritable bowel syndrome. The aim of this report was to describe 20 selected patients with FM without CD who improved when placed on a gluten-free diet. An anti-transglutaminase assay, duodenal biopsy, and HLA typing were performed in all cases. CD was ruled out by negative anti-transglutaminase assay results and absence of villous atrophy in the duodenal biopsy. All patients had intraepithelial lymphocytosis without villous atrophy. Clinical response was defined as achieving at least one of the following scenarios: remission of FM pain criteria, return to work, return to normal life, or the discontinuation of opioids. The mean follow-up period was 16 months (range 5-31). This observation supports the hypothesis that non-celiac gluten sensitivity may be an underlying cause of FM syndrome.

Concepts: Medical terms, Wheat, Constipation, Irritable bowel syndrome, Coeliac disease, Gluten, Gluten-free diet, Dermatitis herpetiformis

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The literature suggests a lack of consensus on the use of terms related to coeliac disease (CD) and gluten.

Concepts: Wheat, Coeliac disease, Gluten, Gluten-free diet, Wheat allergy, Gliadin

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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

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Human and animal studies strongly suggest that dietary gluten could play a causal role in the etiopathogenesis of type 1 diabetes (T1D). However, the mechanisms have not been elucidated. Recent reports indicate that the intestinal microbiome has a major influence on the incidence of T1D. Since diet is known to shape the composition of the intestinal microbiome, we investigated using non-obese diabetic (NOD) mice whether changes in the intestinal microbiome could be attributed to the pro- and anti-diabetogenic effects of gluten-containing and gluten-free diets, respectively. NOD mice were raised on gluten-containing chows (GCC) or gluten-free chows (GFC). The incidence of diabetes was determined by monitoring blood glucose levels biweekly using a glucometer. Intestinal microbiome composition was analyzed by sequencing 16S rRNA amplicons derived from fecal samples. First of all, GCC-fed NOD mice had the expected high incidence of hyperglycemia whereas NOD mice fed with a GFC had significantly reduced incidence of hyperglycemia. Secondly, when the fecal microbiomes were compared, Bifidobacterium, Tannerella, and Barnesiella species were increased (p = 0.03, 0.02, and 0.02, respectively) in the microbiome of GCC mice, where as Akkermansia species was increased (p = 0.02) in the intestinal microbiomes of NOD mice fed GFC. Thirdly, both of the gluten-free chows that were evaluated, either egg white based (EW-GFC) or casein based (C-GFC), significantly reduced the incidence of hyperglycemia. Interestingly, the gut microbiome from EW-GFC mice was similar to C-GFC mice. Finally, adding back gluten to the gluten-free diet reversed its anti-diabetogenic effect, reduced Akkermansia species and increased Bifidobacterium, Tannerella, and Barnesiella suggesting that the presence of gluten is directly responsible for the pro-diabetogenic effects of diets and it determines the gut microflora. Our novel study thus suggests that dietary gluten could modulate the incidence of T1D by changing the gut microbiome.

Concepts: Gut flora, Nutrition, Diabetes mellitus, Diabetes mellitus type 1, Diabetes, Blood sugar, Gluten-free diet, NOD mice

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Gluten-free diets have gained popularity with the public at a rate greater than would be expected based on the prevalence of gluten-related disorders such celiac disease, nonceliac gluten sensitivity, and wheat allergy. This article reviews gluten-related disorders, indications for gluten-free diets, and the possible health benefits of gluten. Despite the health claims for gluten-free eating, no published experimental evidence supports weight-loss with a gluten-free diet or suggests that the general population would benefit from avoiding gluten.

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

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OBJECTIVES: The previous finding of an immunologic response primarily directed against transglutaminase (TG)6 in patients with gluten ataxia (GA) led us to investigate the role of TG6 antibodies in diagnosing GA. METHODS: This was a prospective cohort study. We recruited patients from the ataxia, gluten/neurology, celiac disease (CD), and movement disorder clinics based at Royal Hallamshire Hospital (Sheffield, UK) and the CD clinic, Tampere University Hospital (Tampere, Finland). The groups included patients with idiopathic sporadic ataxia, GA, and CD, and neurology and healthy controls. All were tested for TG6 antibodies. Duodenal biopsies were performed in patients with positive serology. In addition, biopsies from 15 consecutive patients with idiopathic sporadic ataxia and negative serology for gluten-related disorders were analyzed for immunoglobulin A deposits against TG. RESULTS: The prevalence of TG6 antibodies was 21 of 65 (32%) in idiopathic sporadic ataxia, 35 of 48 (73%) in GA, 16 of 50 (32%) in CD, 4 of 82 (5%) in neurology controls, and 2 of 57 (4%) in healthy controls. Forty-two percent of patients with GA had enteropathy as did 51% of patients with ataxia and TG6 antibodies. Five of 15 consecutive patients with idiopathic sporadic ataxia had immunoglobulin A deposits against TG2, 4 of which subsequently tested positive for TG6 antibodies. After 1 year of gluten-free diet, TG6 antibody titers were significantly reduced or undetectable. CONCLUSIONS: Antibodies against TG6 are gluten-dependent and appear to be a sensitive and specific marker of GA.

Concepts: Immune system, Antibody, Hospital, Wheat, Coeliac disease, Gluten-free diet, Royal Hallamshire Hospital, University of Sheffield

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BACKGROUND:: Patients with Celiac Disease (CD) have a wide variety of symptoms, from being asymptomatic to having chronic diarrhea, abdominal pain and extra-intestinal symptoms. In the oral cavity, enamel defects and recurrent aphthous stomatitis are the most common symptoms. AIM:: To assess oral health, bacterial colonization and salivary buffering capacity of patients with CD at diagnosis were compared with CD patients on gluten free diet (GFD) and healthy children. METHODS:: Three groups were prospectively investigated: newly diagnosed celiac disease, celiac disease treated with GFD and a control group. All children were examined by pediatric dentists and saliva samples were collected for bacterial and pH analysis. RESULT:: Ninety children were enrolled in the study, thirty in each group. A higher prevalence of enamel hypoplasia (66%) was found in celiac children. Plaque Index was significantly lower in the celiac treated group, which correlated with oral health behavior: teeth brushing and frequency of eating between meals. Children on GFD brushed their teeth and used fluoride significantly more often than other children in the study. No difference between groups was found in snacks consumption, Mutans Streptococci and Lactobacilli counts in saliva, as well as pH and buffer capacity, CONCLUSIONS:: A lower degree of plaque was found in celiac children on GFD. This finding could not be explained by salivary properties or bacteria, but rather by better oral hygiene. The results should raise the awareness of pediatric gastroenterologists to oral health related issues in children with CD.

Concepts: Bacteria, Wheat, Crohn's disease, Buffer solution, Coeliac disease, Gluten, Aphthous ulcer, Gluten-free diet