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Grown-up coeliac children: the effects of only a few years on a gluten-free diet in childhood.

AIM: To evaluate clinical and psychological status of adults with childhood diagnosis of coeliac disease who were re-exposed to gluten after only a few years and now on a gluten-containing diet, compared with adults with recent diagnosis of coeliac disease, and adults who remained on gluten-free diet after childhood diagnosis. METHODS: A total of 195 adults with a biopsy suggestive of coeliac disease in childhood, who either had adhered to a gluten-free diet for at least 1 year after diagnosis and now are either on gluten-free diet (n = 110) or on gluten-containing diet (n = 85), and adults with newly diagnosed coeliac disease (n = 165) underwent a medical check-up. RESULTS: Body mass index and main laboratory indices were statistically different among groups (lowest in never on gluten-free diet, highest in gluten-free diet). The lowest average levels of bone mineral density were found among never on gluten-free diet patients. Prevalence of autoimmune disorders was increased in never on gluten-free diet when compared with the transient gluten-free diet and gluten-free diet groups. Histology revealed villous subatrophy in all patients of never on gluten-free diet group, in 39 of 110 patients of gluten-free diet and in 84 of 85 of transient gluten-free diet groups. Herpetiform dermatitis was found in three patients of gluten-free diet, three of transient gluten-free diet and three of never on gluten-free diet. Dental enamel defects were found in 15 patients of transient gluten-free diet, 43 of never on gluten-free diet and in zero of the gluten-free diet group. Pregnancy outcome was not significantly different between the two groups, but neonatal weight was lower and breast feeding was shorter in the never on gluten-free diet group. Sexual habits, alcohol intake and cigarette smoking were significantly different in the never on gluten-free diet group when compared with the other two groups. CONCLUSION: Gluten withdrawal in childhood partly protects coeliac adults from clinical and behavioural effects of gluten sensitivity.

Adolescent↗

Optimal wet corn gluten and protein levels in steam-flaked corn-based finishing diets for steer calves.

A feeding trial evaluated the hypothesis that wet corn gluten feed would improve growth performance of cattle fed steam-flaked corn-based finishing diets and supply required degradable intake protein (DIP). The trial used 360 steer calves (initial BW = 288 +/- 11 kg) housed in 36 pens for 166 d in an incomplete 4 x 3 factorial arrangement of treatments. Pens of steers were assigned to treatments according to a completely randomized design (four replicates per treatment combination). Treatments were wet corn gluten feed (0, 20, 30, or 40% of dietary DM) and CP (13.0, 13.7, or 14.4% of dietary DM) via supplemental urea as DIP. The 0% wet corn gluten feed treatment included only the 13.7% CP diet, and the 40% wet corn gluten feed treatment included only the 13.7 and 14.4% CP diets. Final dietary DIP concentration was 9.0% for 0% wet corn gluten feed; 8.7, 9.5, and 10.2% for 20% wet corn gluten feed; 9.0, 9.7, and 10.3% DIP for 30% wet corn gluten feed; and 10.0 and 10.6% for 40% wet corn gluten feed. Hot carcass weight, ADG, DMI, and G:F responded quadratically (P < or = 0.05) to wet corn gluten feed. The 20, 30, and 40% wet corn gluten feed treatments increased ADG by 7, 6, and 3% and increased DMI by 4, 5, and 5%, respectively, relative to the 0% wet corn gluten feed treatment. Feed efficiency was 102, 101, and 98% of the 0% wet corn gluten feed treatment for 20, 30, and 40% wet corn gluten feed, respectively. Hot carcass weight, ADG, and G:F increased linearly (P < or = 0.05) in response to increased DIP. Nonlinear analysis for DIP over the combined 20 and 30% wet corn gluten feed treatments indicated a DIP requirement of 9.6% of DM for ADG and 9.2% of DM for G:F, corresponding to 14.6 and 14.3% CP for 20% wet corn gluten feed and 14.8 and 14.5% CP for 30% wet corn gluten feed, respectively. Fat thickness, marbling, LM area, and USDA yield grade were not affected (P = 0.12 to 0.99) by wet corn gluten feed or CP. These results show that the inclusion rate of wet corn gluten feed for maximizing ADG and G:F in steam-flaked corn-based finishing diets is approximately 20% of DM. The DIP requirement determined in this trial averaged 9.4% of DM.

Animal Feed↗

Serum prolactin levels after administration of the alimentary opioid peptide gluten exorphin B4 in male rats.

Gluten Exorphins are opioid peptides identified in enzymatic digests of gluten. The effects of Gluten Exorphins are still largely unknown. It has been shown that Gluten Exorphin B5 (Tyr-Gly-Gly-Trp-Leu) stimulates Prolactin secretion in male rats. In this study, we have evaluated the Prolactin response to Gluten Exorphin B4, another exorphin whose structure (Tyr-Gly-Gly-Trp) is identical to that of the NH(2)-terminal sequence of Gluten Exorphin B5. To this aim, five groups of male rats were given the following intravenous treatments: vehicle, Gluten Exorphin B5 3 mg kg-1 body weight, Gluten Exorphin B4 at the doses of 3, 6 and 9 mg kg-1 body weight. At the dose of 3 mg kg-1 body weight, Gluten Exorphin B5 induced a significant increase in Prolactin levels. Gluten Exorphin B4 could not modify Prolactin secretion, even when administered at doses three times higher than those effective for Gluten Exorphin B5. The present study: (1) indicates that Gluten Exorphin B4 does not modify Prolactin secretion in male rats; (2) confirms the ability of Gluten Exorphin B5 to exert a stimulatory action on Prolactin release; (3) suggests that the presence of the carboxy-terminal leucine in Gluten Exorphin B5 is essential for its action on Prolactin secretion.

Amino Acid Sequence↗

Elimination of dietary gluten does not reduce titers of type 1 diabetes-associated autoantibodies in high-risk subjects.

OBJECTIVE: Removal of the dietary wheat protein gluten protects against autoimmune diabetes in animal models. Furthermore, elimination of dietary gluten reduces the frequency of type 1 diabetes in patients with celiac disease. Herein we test the hypothesis that gluten is the driving antigen for type 1 diabetes-associated islet autoimmunity. RESEARCH DESIGN AND METHODS: Seven autoantibody-positive, first-degree relatives of patients with type 1 diabetes were placed on a gluten-free diet for 12 months followed by gluten reexposure for 12 months. Gliadin antibodies as well as the diabetes-related antibodies insulin autoantibody (IAA), GAD antibody (GADA), and tyrosin phosphatase IA2 antibody (IA-2A) were measured every 3 months; oral glucose tolerance tests were performed every 6 months. Changes in autoantibody titers were compared with those observed in a matched historical cohort. RESULTS: A reduction in IgG gliadin antibody titers was observed during the gluten-free period, but titers of diabetes-associated autoantibodies changed independently of gluten exposure. Type 1 diabetes-associated islet autoantibody levels at the end of the gluten-free diet period were not significantly different from those before commencement of the diet (P = 0.2) or at the end of the gluten reexposure period (P = 0.4). Changes in individual subjects were identified, but no differences were noted between the gluten-free and the gluten re-exposure periods, and the changes were similar to those observed in the historical control cohort (P = 1.0). Major titer reductions (>50%) in the gluten-free period were observed in only one subject for all antibodies. Type 1 diabetes developed in this subject and in a second subject during the gluten reexposure period. CONCLUSIONS: The findings do not support the hypothesis that gluten is a driving antigen in type 1 diabetes.

Animals↗

Effects of gluten enriched diet on the small intestinal mucosa of normal mice and mice with graft versus host reaction.

This study looked at the effect of extra dietary gluten on the intestinal architecture of both normal mice and those with an ongoing mucosal delayed hypersensitivity reaction. BDF1 normal mice and mice in which a graft v host reaction (GvHR) had been induced, both weaned on gluten free diet, were allocated for three weeks to three different dietary regimens: gluten free, 'normal' (3.6% gluten), and gluten enriched (15.8% gluten). In normal mice receiving the gluten containing diet, shorter villi, deeper crypts, and higher crypt cell production rate were noted when compared with those receiving gluten free diet: these changes were more pronounced in those receiving the gluten enriched diet. GvHR mice showed shorter villi and an increase in both crypt length and crypt cell production rate when compared with normal mice, but the presence of gluten in their diet did not produce additional damage. Both in normal and in GvHR mice receiving gluten containing diet there were no signs of systemic (cell mediated or humoral) or mucosal immune reactions (raised intraepithelial lymphocyte counts or enhanced epithelial Ia expression) to gliadin. In conclusion, increasing the dietary gluten content produces significant changes in the mucosal architecture of normal mice; mice with GvHR enteropathy do not show additional damage resulting from dietary gluten.

Animals↗

Wheat starch, gliadin, and the gluten-free diet.

Individuals with celiac disease generally are advised to follow a lifelong gluten-free diet and avoid consumption of the prolamins gliadin (wheat), secalin (rye), and hordein (barley). Although the designation of the diet as glutenfree may imply that the diet contains zero gluten, this is not necessarily true. In some countries (eg, United States, Canada), the gluten-free diet is completely devoid of gluten and is based on foods such as rice and corn that are naturally gluten free. In others (eg, Scandinavia, United Kingdom), the gluten-free diet may include foods such as wheat starch that have been rendered gluten free but nonetheless contain small amounts of toxic prolamins. The discrepancy in the use of foods rendered gluten free exists because the amount of toxic prolamins that individuals with celiac disease may consume without damaging the mucosa of the small intestine is unknown. Minimal research has been conducted on the toxicity of foods rendered gluten free, and there are no definitive data about whether the small amount of prolamin found in these products is safe to consume. Nonetheless, the Codex Alimentarius Standard for gluten-free foods allows a certain amount of prolamin in foods designated gluten free, and these products have been used in many countries for several decades. Well-designed, scientifically sound studies are needed to help determine the amount of toxic prolamins, if any, that may be safely consumed by individuals with celiac disease. Until this research is conducted, dietitians in the United States should continue to advise their patients against the use of wheat starch and other foods rendered gluten free.

Celiac Disease↗

Impact of protein size distribution on gluten thermal reactivity and functional properties.

Wheat gluten structure was modified in different ways: Disulfide bonds were reduced by sulfitolysis, or protein chains were enzymatically hydrolyzed at three different degrees of proteolysis. A kinetic study of the thermal reactivity of the modified glutens showed that gluten aggregation kinetic was slowed in consequence to the shift of gluten size distribution toward smaller proteins. In contrary to sulfitolysis, proteolysis also affected the gluten reactivity potential because of the formation of numerous nonreactive species. Moreover, the thermally induced browning reaction was greatly enhanced by proteolysis, which increased the amount of free amine residues, substrates of the Maillard reaction. On the contrary, a whitening effect was observed for reduced gluten with bisulfite. Proteolysis was also found to decrease plasticized gluten viscosity, to increase gluten-based materials water solubility, and to enhance gluten adhesiveness properties but to reduce its mechanical performance. Sulfitolysis was considered as a possible way of extending gluten processability by extrusion or injection molding, whereas proteolysis was found to confer enhanced gluten stickiness that suggests new potential end uses of gluten in the pressure sensitive adhesives domain.

Chemical Phenomena↗

The daily gluten intake in relatives of patients with coeliac disease compared with that of the general Dutch population.

BACKGROUND: It has been suggested that the amount of gluten intake in populations offers an explanation for differences in the epidemiology of coeliac disease. Investigations into first-degree relatives of coeliac disease patients have often shown that relatives exhibit intermediate features of coeliac disease, possibly due to a low gluten intake. AIMS: The aim of this study was to investigate the pattern of gluten consumption in the general Dutch population for different age and sex groups and for different product groups, and to investigate the daily gluten intake of first-degree relatives of coeliac disease patients. METHODS: Questionnaires concerning the gluten intake of 55 first-degree relatives of coeliac disease patients were analysed. To determine the gluten intake of the general Dutch population, the results of a mass investigation were used. The amount of gluten in the gluten-rich products was estimated by multiplying the amount of vegetable proteins by 0.8. RESULTS: The median daily gluten intake of the relatives was 12.9 g (range: 3.8-31.3). The mean daily gluten intake of the study population in the Netherlands was 1 3.1 g. CONCLUSION: The gluten intake of first-degree relatives of coeliac disease patients was the same as that of the general population. Thus, a low gluten intake apparently does not explain the aspecific presentation and prevalence of coeliac disease in first-degree relatives of coeliac disease patients.

Adolescent↗

Dietary treatment of gluten ataxia.

BACKGROUND: Gluten ataxia is an immune mediated disease, part of the spectrum of gluten sensitivity, and accounts for up to 40% of cases of idiopathic sporadic ataxia. No systematic study of the effect of gluten-free diet on gluten ataxia has ever been undertaken. OBJECTIVE: To study the effect of gluten-free diet on patients presenting with ataxia caused by gluten sensitivity. METHODS: 43 patients with gluten ataxia were studied. All were offered a gluten-free diet and monitored every six months. All patients underwent a battery of tests to assess their ataxia at baseline and after one year on diet. Twenty six patients (treatment group) adhered to the gluten-free diet and had evidence of elimination of antigliadin antibodies by one year. Fourteen patients refused the diet (control group). Three patients had persistently raised antigliadin antibodies despite adherence to the diet and were therefore excluded from the analysis. RESULTS: After one year there was improvement in ataxia reflected in all of the ataxia tests in the treatment group. This was significant when compared with the control group. The diet associated improvement was apparent irrespective of the presence of an enteropathy. CONCLUSIONS: Gluten ataxia responds to a strict gluten-free diet even in the absence of an enteropathy. The diagnosis of gluten ataxia is vital as it is one of the very few treatable causes of sporadic ataxia.

Adult↗

Gluten sensitivity of small intestinal mucosa in vitro: quantitative assessment of histologic change.

In view of the importance to the patient of demonstrating mucosal sensitivity to gluten we have quantitated morphologic change during organ culture of small bowel mucosa by measuring enterocyte height. In 27 normal controls the mean preculture enterocyte height was 28.3 micrometer +/- 1.8 (+/- 1 SD), decreasing to 25.6 micrometer +/- 1.9 and 26.1 micrometer +/- 2.0 after 24 h culture in the absence and presence of gluten, respectively. Both these decreases were significant (p < 0.001), but there was no difference between culture with or without gluten. In 9 abnormal controls, the mean preculture enterocyte height was 27.0 micrometer +/- 2.7, decreasing significantly (p < 0.05) to 24.5 micrometer +/- 1.1 after 24 h culture without gluten, and to 25.4 micrometer +/- 2.3 with gluten (NS). In 17 untreated celiac patients, the mean preculture enterocyte height was 19.6 micrometer +/- 1.9 increasing significantly to 23.8 micrometer +/- 2.0 (p < 0.001) after 24 h culture without gluten but decreasing to 18.7 micrometer +/- 3.1 after 24 h culture with gluten (NS). There was a significant difference between culture with or without gluten (p < 0.001). In 21 treated celiac patients, the mean preculture enterocyte height was 28.1 micrometer +/- 1.9 decreasing to 25.4 micrometer +/- 2.0 and 24.2 +/- 1.9 in the absence and presence of gluten, respectively. Both these decreases were significant (p < 0.001), but more importantly there was a significant decrease (p < 0.001) after culture with gluten compared with culture without gluten. These data indicate that it is possible to quantify morphologic change during organ culture and to demonstrate gluten-sensitivity not only in untreated, but also in treated celiac mucosa. These studies have important implications as regards the diagnosis and further investigation of the etiology of celiac disease.

Caseins↗

Intestinal permeability in long-term follow-up of patients with celiac disease on a gluten-free diet.

Intestinal permeability is frequently abnormal in patients with celiac disease. The long-term effect of a gluten-free diet on intestinal permeability and the correlation of intestinal permeability with a gluten-free diet are not known. The objectives of this study were to determine the responses of intestinal permeability and antibody testing to gluten free diet and the degree of correlation of these measurements with gluten ingestion. In this prospective study, patients with celiac disease were divided into three groups based on length of time on a gluten-free diet: Group A, < 1 month; Group B, 1 month-1 year; Group C, > 1 year. Patients in Groups B and C were tested at baseline and at 4-12 weeks later for the following: lactulose/mannitol intestinal permeability, endomysial antibody, and 3-day food record. Permeability tests were also performed in Group A and control subjects. Intestinal permeability was elevated in newly diagnosed celiac disease and in individuals on a gluten-free diet for less than 1 year. Intestinal permeability was normal in 80% at visit 1 and 87% at visit 2 in individuals with celiac disease on a gluten-free diet for more than a year. Trace gluten ingestion was associated with increased intestinal permeability on visit 2 (P = 0.0480). The sensitivity of detecting gluten ingestion as measured by a 3-day food record was higher for permeability testing (29 and 36%) compared with endomysial antibody testing (18 and 18%) for visits 1 and 2, respectively. Intestinal permeability normalizes in the majority of individuals with celiac disease on a gluten-free diet. Gluten ingestion as measured by a 3-day food record correlates with intestinal permeability measurements. The role of permeability testing in the follow-up of patients with celiac disease warrants further investigation.

Adult↗

Intestinal permeability of Irish setter puppies challenged with a controlled oral dose of gluten.

A combined test of intestinal permeability using lactulose (L) and rhamnose (R), and absorptive function using xylose (X) and 3-O-methylglucose (G), was carried out at four, six, eight and 16 weeks of age in 22 healthy control and six gluten-sensitive Irish setter (IS) dogs fed a diet containing a controlled dose of gluten from weaning. Comparisons were made with two groups of 12 healthy control dogs of breeds other than IS, one fed the same diet as the setters and the other fed a gluten-free diet. Gluten-sensitive IS showed a rise in permeability (mean [SEM] urinary L/R) from 0.23 (0.07) at four weeks to 0.39 (0.05) at eight weeks, remaining at 0.36 (0.04) at 16 weeks. These results were significantly higher in gluten-sensitive than control IS at six, eight and 16 weeks, compatible with jejunal biopsy lesions characteristic of gluten-sensitive enteropathy demonstrated in affected dogs at 16 weeks. Urinary L/R ratios of control dogs of breeds other than IS peaked at six weeks 0.27 (0.02), and were significantly higher than those of control IS at six and eight weeks, demonstrating differences in permeability between Irish setter dogs and other breeds at this age. There were no significant differences in urinary X/G ratios at six, eight and 16 weeks of age between any of the groups of dogs challenged with gluten. Urinary L/R and X/G ratios were similar in the control dogs of breeds other than IS fed gluten-containing and gluten-free diets. These findings indicate that intestinal permeability testing of puppies during controlled oral gluten challenge provides a practical screening test for gluten sensitivity in Irish setter dogs at an early age.

Administration, Oral↗

Wheat gluten used as a clarifying agent of red wines.

Bovine spongiform encephalopathy caused a situation of crisis leading the public and winemakers to lose their confidence in the use of gelatin as a fining agent and to reject animal proteins in general. Therefore, we started the search for a substitute for gelatin and egg protein by comparing gluten with these fining treatments currently used. This study concerned the fining of a Burgundy red wine (Rully, Controlled Appellation). For 6 g/hL, enzymatically hydrolyzed glutens (EHG) gave better efficiencies than deamidated glutens. The efficiency of the egg proteins treatment was situated between those of the hydrolyzed glutens and deamidated glutens. For 12 and 18 g/hL, turbidities of the wine treated by five glutens were 67 to 86% less than that of the control wine. Better results were obtained with egg proteins for short kinetics particularly. Wine fining with gluten was always better than gelatin treatments. The differences between the five glutens became very small when the dose incorporated in the wine increased. The volumes of lees generated by fining with gluten are situated between the values obtained with egg proteins and gelatin. After fining, immunodetection with gluten polyclonal antibodies failed to detect residual deamidated gluten.

Deamination↗

Gluten sensitivity in patients with primary biliary cirrhosis.

OBJECTIVE: Whereas celiac disease and primary biliary cirrhosis have been reported to coexist in the same patient, the frequency of this relationship has not been clarified. Nowadays, the concept of celiac disease has been extended from that of a severe enteropathy to a broader concept of gluten-driven intestinal immunological response. In this study we assessed features of gluten sensitivity in a cohort of patients with primary biliary cirrhosis. METHODS: Ten patients with primary biliary cirrhosis were evaluated a mean of 2 yr after diagnosis. The following features of gluten sensitivity were assessed: serum antigliadin and endomysial antibodies, small bowel histology (degree of atrophy and quantitative histological parameters), the presence of the typical celiac HLA genotype (DQ2), and intraepithelial lymphocyte response in the rectal mucosa after local gluten instillation (rectal gluten challenge). RESULTS: Overall, three patients presented evidence of gluten sensitivity. All three had abnormal titers of antigliadin antibody type IgA and one was positive for endomysial antibody. Two patients had partial villous atrophy. The rectal gluten challenge showed a celiac-like response, evidenced by an increase in intraepithelial lymphocyte infiltration after gluten exposure, in the three patients. The characteristic celiac HLA genotypes (DQA1 0501 and DQB1 0201) were identified in three patients. One of them also exhibited other features of gluten sensitivity. However, despite evidence of gluten intolerance, patients had minimal or no symptoms characteristic of celiac disease. CONCLUSION: We detected features of gluten sensitivity in a high proportion of patients with primary biliary cirrhosis. Further studies should be performed to elucidate the clinical significance of this association.

Adult↗

Interactions between forage and wet corn gluten feed as sources of fiber in diets for lactating dairy cows.

Twelve early lactation Holstein cows (4 fistulated) were used in replicated 4x4 Latin squares with 4-wk periods to determine the effective neutral detergent fiber (NDF) content of wet corn gluten feed and to measure the effect of forage particle size on ruminal mat consistency and passage rate of wet corn gluten feed. Diets were 1) 23.3% NDF (17.4 percentage units of NDF from alfalfa silage), 2) diet 1 plus 11.1 additional percentage units of NDF from alfalfa silage, 3) diet 1 plus 10.7 percentage units of NDF from wet corn gluten feed, and 4) 8.6 percentage units of NDF from alfalfa silage plus 8.9 percentage units of NDF from coarsely chopped alfalfa hay and 10.7 percentage units of NDF from wet corn gluten feed. The calculated effective NDF factor for wet corn gluten feed, using change in milk fat concentration per unit change in NDF, was 0.74 compared with an assumed 1.0 for alfalfa silage. Rumination activity was measured to calculate a physically effective NDF factor for wet corn gluten feed, which was only 0.11 compared with 1.0 for alfalfa silage. Physically effective NDF also was determined for wet corn gluten feed by wet sieving; 22% of the particles were retained on the 3.35-mm screen or greater. Ruminal mat consistency increased and passage rate of wet corn gluten feed decreased with added hay. The inclusion of chopped alfalfa hay to a diet containing wet corn gluten feed increased ruminal mat consistency, rumination activity, and slowed passage rate, resulting in greater ruminal digestion of NDF from wet corn gluten feed. Depending on the response variable, the effectiveness of NDF from wet corn gluten feed varied from 0.11 to 0.74.

Animal Feed↗