Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet

BACKGROUND The gluten-free diet(GFD)has limitations,and there is intense research in the development of adjuvant therapies.AIM To examine the effects of orally administered Aspergillus niger prolyl endopeptidase protease(AN-PEP)on inadvertent gluten exposure and symptom prevention in adult celiac disease(CeD)patients following their usual GFD.METHODS This was an exploratory,double-blind,randomized,placebo-controlled trial that enrolled CeD patients on a long-term GFD.After a 4-wk run-in period,patients were randomized to 4 wk of two AN-PEP capsules(GliadinX;AVI Research,LLC,United States)at each of three meals per day or placebo.Outcome endpoints were:(1)Average weekly stool gluten immunogenic peptides(GIP)between the run-in and end of treatments and between AN-PEP and placebo;(2)celiac symptom index(CSI);(3)CeD-specific serology;and(4)quality of life.Stool samples were collected for GIP testing by ELISA every Tuesday and Friday during run-ins and treatments.RESULTS Forty patients were randomized for the intention-to-treat analysis,and three were excluded from the per-protocol assessment.Overall,628/640(98.1%)stool samples were collected.GIP was undetectable(<0.08μg/g)in 65.6%of samples,and no differences between treatment arms were detected.Only 0.5%of samples had GIP concentrations sufficiently high(>0.32μg/g)to potentially cause mucosal damage.Median GIP concentration in the AN-PEP arm was 44.7%lower than in the run-in period.One-third of patients exhibiting GIP>0.08μg/g during run-in had lower or undetectable GIP after AN-PEP treatment.Compared with the run-in period,the proportion of symptomatic patients(CSI>38)in the AN-PEP arm was significantly lower(P<0.03).AN-PEP did not result in changes in specific serologies.CONCLUSION This exploratory study conducted in a real-life setting revealed high adherence to the GFD.The AN-PEP treatment did not significantly reduce the overall GIP stool concentration.However,given the observation of a significantly lower prevalence of patients with severe symptoms in the AN-PEP arm,further clinical research is warranted.

A novel AgNPs/MOF substrate-based SERS sensor for high-sensitive on-site detection of wheat gluten

Gluten,known as the major allergen in wheat,has gained increasing concerns in industrialized countries,resulting in an urgent need for accurate,high-sensitive,and on-site detection of wheat gluten in complex food systems.Herein,we proposed a silver nanoparticles(AgNPs)/metal-organic framework(MOF)substrate-based surface-enhanced Raman scattering(SERS)sensor for the high-sensitive on-site detection of wheat gluten.The detection occurred on the newly in-situ synthesized AgNPs/MOF-modified SERS substrate,providing an enhancement factor(EF)of 1.89×10^(5).Benefitting from the signal amplification function of AgNPs/MOF and the superiority of SERS,this sensor represented high sensitivity performance and a wide detection range from 1×10^(-15)mol/L to 2×10^(-6)mol/L with a detection limit of 1.16×10^(-16)mol/L,which allowed monitoring the trace of wheat gluten in complex food system without matrix interference.This reliable sandwich SERS sensor may provide a promising platform for high-sensitive,accurate,and on-site detection of allergens in the field of food safety.

Agro-Morphology Evaluation and Gluten Content Estimation of Wheat (Triticum aestivum L.) in the Western Highland of Cameroon

Agriculture is amongst the major occupations in Cameroon where over 70% of citizens are involved and it contributes enormously to the economy of the country. Wheat is one of the most consumed cereals in Cameroon with very high importation rate. However, the adoption of wheat production in the cropping system could have the potential to pull farmers out of poverty. It is essential in human foods and animal feeds. This study aims to investigate on the adaptability of wheat varieties based on growth traits and yield as well as to estimate the gluten content in each of the tested variety in the North-West region. Eight wheat varieties (five from CIMMYT, two from IRAD and one local variety) were evaluated in a factorial design with two types of fertilization (organic and inorganic), in two site (Santa and UBa farm) and five environments. Agro-morphological data were collected and were subjected to the analysis of variance using R software. The gluten content related to the baking quality of wheat flour was estimated per tested variety. Highly significant differences were observed among varieties, sites, environment and fertilization for all parameters estimated. The general mean of all the traits evaluated was significantly higher when using organic fertilizer than inorganic, meaning that the application of organic fertilizer provides better performance of wheat growth. The elevated number of tillers found in Santa could inform on the high level of soil fertility for wheat production in that area. Environment 1 was found to be the best follow by environment 3 and 5. IRAD I gave the highest yield followed by Alexander Wonder and IRAD II. 11SATYND and 29SAWYT were promising introduced varieties in term of grain weight when using organic fertilization. Wet and dry gluten yield varied from 3.8 (ALEXANDER Wonder) to 5.5 (IRAD I) and from 3.7 (IRAD II) to 7.9 (IRAD I) respectively. All the introduced wheat varieties expressed low wet and dry gluten yield as compare to the check Amigo. IRAD I was the best variety to be produced for industrial purposes taken into account the high level of gluten content. IRAD I, 42ESWYTB and IRAD II were found to have their moisture content percentage of flour below that of the check (Amigo) and therefore could be recommended for manufactured foods.

Beyond the gluten-free diet:Innovations in celiac disease therapeutics

Celiac disease(CD)is an autoimmune disorder exacerbated by the ingestion of gluten in genetically susceptible individuals,leading to intestinal inflammation and damage.This chronic disease affects approximately 1%of the world’s po-pulation and is a growing health challenge due to its increasing prevalence.The development of CD is a complex interaction between genetic predispositions and environmental factors,especially gluten,culminating in a dysregulated immune response.The only effective treatment at present is a strict,lifelong gluten-free diet.However,adherence to this diet is challenging and often incomplete,so research into alternative therapies has intensified.Recent advances in under-standing the molecular and immunological aspects of CD have spearheaded the development of novel pharmacologic strategies that should provide more effec-tive and manageable treatment options.This review examines the latest inno-vations in CD therapies.The focus is on drugs in advanced clinical phases and targeting specific signaling pathways critical to the disease pathogenesis.We dis-cuss both quantitative strategies such as enzymatic degradation of gluten,and qualitative approaches including immunomodulation and induction of gluten tolerance.Innovative treatments currently under investigation include transglu-taminase inhibitors,which prevent the modification of gluten peptides,and nano-particle-based therapies to recalibrate the immune response.These new therapies not only promise to improve patient outcomes but are also expected to improve quality of life by reducing the burden of dietary restrictions.The integration of these new therapies could revolutionize the treatment of CD and shift the para-digm from strict dietary restrictions to a more flexible and patient-friendly thera-peutic approach.This review provides a comprehensive overview of the future prospects of CD treatment and emphasizes the importance of continued research and multidisciplinary collab-oration to integrate these advances into standard clinical practice.

Autoantibodies related to ataxia and other central nervous system manifestations of gluten enteropathy

Gluten ataxia and other central nervous system disorders could be linked to gluten enteropathy and related autoantibodies.In this narrative review,we focus on the various neuro-logical manifestations in patients with gluten sensitivity/celiac disease,immunological and autoimmune mechanisms of ataxia in connection to gluten sensitivity and the autoantibodies that could be used as a biomarker for diagnosing and following.We focused on the anti-gliadin antibodies,antibodies to different isoforms of tissue transglutaminase(TG)(anti-TG2,3,and 6 antibodies),anti-glycine receptor antibodies,anti-glutamine acid decarboxylase antibodies,anti-deamidated gliadin peptides antibodies,etc.Most studies found a higher prevalence of these antibodies in patients with gluten sensitivity and neurological dysfunction,presented as different neurological disorders.We also discuss the role of a gluten-free diet on the clinical improvement of patients and also on imaging of these disorders.

Validation of Molecular Detection Methods for Gluten Allergens in Infant Formula

[Objectives]To verify the specificity,sensitivity,precision and negative-positive deviation of the foodproof gluten component de-tection kit for the detection of gluten allergens in milk powder matrix,and to establish a real-time fluorescent PCR legal method for the detec-tion of gluten allergens in milk powder.[Methods]The specificity,sensitivity,precision and negative-positive deviation of the detection method of foodproof gluten component detection kit(PCR-probe method)were verified by artificially adding different concentrations of wheat bran and extracting sample DNA by kit method,and applied to sample detection.[Results] The specific detection results of two kinds of milk powder with wheat bran and buckwheat added showed that the foodproof gluten component detection kit(PCR-probe method)had good speci-ficity for wheat gluten.The results of artificially added wheat bran positive samples showed that the false positive rate and false negative rate of the kit in the milk powder matrix were O,and the sensitivity and precision were high.[Conclusions]The kit is simple to operate and has high accuracy,which is suitable for the detection of gluten allergen components in milk powder.

Study and Formulation of Composite Flours Based on Gluten Flour and Local Cereal Flours: Fonio, Millet and Sorghum

This study makes it possible to establish baking flours of nutritional quality and technologically acceptable following the increase in their rheological parameters due to the insertion of gluten flour. The composite flours were obtained using the Philips mixer type (model HR2811). The nutritional qualities of the formulated flours were determined by the Kjeldahl, AOAC 985-29, UV-VIS spectrophotometry (DR 5000;HACH and LANGE, France) and Soxhlet gravimetric methods. The compounds obtained are respectively: Protein, carbohydrate, lipid, micronutrient and vitamin contents. Monitoring the analysis of functional properties (water and oil absorption capacity) as well as baking value.

Optimization of Hydrolysis Conditions for Corn Gluten Meal

[Objective] To investigate the optimal enzyme for the hydrolysis of corn gluten meal and the optimal hydrolysis conditions for the enzyme. [Method] Nine kinds of enzymes were used to hydrolyze the corn gluten meal, using the formaldehyde titration method for the determination of hydrolysis degree, and orthogonal test was used to determine the optimal hydrolysis conditions for double enzymes hydrol- ysis of corn gluten meal. [Result] The optimal pretreatment condition for corn gluten meal is heating at 121 ~C for 30 min. The double enzyme hydrolysis for the pro- treated corn gluten meal using 2709 alkaline protease and flavourzyme showed that the degree of hydrolysis could reach 32.4% with enzyme addition amount of 4%, hy- drolysis time of 4 h at 45℃ and pH=7.0. [Conclusion] This study laid the foundation for the study on the preparation of bioactive peptides such as oligopeptide with high F value and antihypertensive peptides, further improving the corn intensive process- ing industrial chain.

Diagnosis of gluten related disorders: Celiac disease, wheat allergy and non-celiac gluten sensitivity

Cereal crops and cereal consumption have had a vital role in Mankind's history. In the recent years gluten ingestion has been linked with a range of clinical disorders. Gluten-related disorders have gradually emerged as an epidemiologically relevant phenomenon with an estimated global prevalence around 5%. Celiac disease, wheat allergy and non-celiac gluten sensitivity represent different gluten-related disorders. Similar clinical manifestations can be observed in these disorders, yet there are peculiar pathogenetic pathways involved in their development. Celiac disease and wheat allergy have been extensively studied, while non-celiac gluten sensitivity is a relatively novel clinical entity, believed to be closely related to other gastrointestinal functional syndromes. The diagnosis of celiac disease and wheat allergy is based on a combination of findings from the patient's clinical history and specific tests, including serology and duodenal biopsies in case of celiac disease, or laboratory and functional assays for wheat allergy. On the other hand, non-celiac gluten sensitivity is still mainly a diagnosis of exclusion, in the absence of clear-cut diagnostic criteria. A multimodal pragmatic approach combining findings from the clinical history, symptoms, serological and histological tests is required in order to reach an accurate diagnosis. A thorough knowledge of the differences and overlap in clinical presentation among gluten-related disorders, and between them and other gastrointestinal disorders, will help clinicians in the process of differential diagnosis.

Effect of Gluten on Pasting Properties of Wheat Starch

The effect of gluten on pasting properties of wheat starch was studied to provide a scientific basis for the application of gluten in food production and quality improvement in wheat breeding. The pasting properties of blends were analyzed using PH 1391 wheat starch mixed with five different additions of three kinds of gluten （strong-, medium-, and weak-gluten） and the structures of network were observed with microscope. The significant downtrends of peak viscosity, trough viscosity, final viscosity, area of viscosity, setback, and peak time were observed with the increase in the addition of gluten. In general, the average value of them decreased respectively by 3.6, 4.8, 3.4, 3.8, 4.0, and 1.18% of those corresponding indexes of pure starch for every 2% increase in gluten. The decreasing rate of the indexes mentioned above exceeded more than 2% except peak time, but there were no significant influence of gluten addition on breakdown, pasting temperature and pasting time. The inter layer composed of gluten was not observed when the addition of gluten was 10%, as the compound formed of gluten inlaid in the paste of starch, but obvious inter layer was detected when the addition of gluten was 18%. There was significant or remarkable difference among the effects of three different kinds of gluten on the peak viscosity, trough viscosity, area of viscosity, setback, and peak time, but it had no significant difference among the effects of different glutens on pasting temperature and pasting time. The descending order of the effect of different glutens on peak viscosity, trough viscosity, and area of viscosity was strong-, medium-, and weak-gluten, but the order of them for setback was opposite. Both addition and types of gluten significantly affected peak viscosity, trough viscosity, area of viscosity, setback, and peak time, but there were no significant effects of it on peak time and peak temperature.

Extra-intestinal manifestations of non-celiac gluten sensitivity: an expanding paradigm

Non celiac gluten sensitivity(NCGS) is a syndrome characterized by a cohort of symptoms related to the ingestion of gluten-containing food in subjects who are not affected by celiac disease(CD) or wheat allergy. The possibility of systemic manifestations in this condition has been suggested by some reports. In most cases they are characterized by vague symptoms such as ‘foggy mind', headache, fatigue, joint and muscle pain, leg or arm numbness even if more specific complaints have been described. NCGS has an immune-related background. Indeed there is a strong evidence that a selective activation of innate immunity may be the trigger for NCGS inflammatory response. The most commonly autoimmune disorders associated to NCGS are Hashimoto thyroiditis, dermatitis herpetiformis, psoriasis and rheumatologic diseases. The predominance of Hashimoto thyroiditis represents an interesting finding, since it has been indirectly confirmed by an Italian study, showing that autoimmune thyroid disease is a risk factor for the evolution towards NCGS in a group of patients with minimal duodenal inflammation. On these bases, an autoimmune stigma in NCGS is strongly supported; it could be a characteristic feature that could help the diagnosis and be simultaneously managed. A possible neurological involvement has been underlined by NCGS association with gluten ataxia, gluten neuropathy and gluten encephalopathy. NCGS patients may show even psychiatric diseases such as depression, anxiety and psychosis. Finally, a link with functional disorders(irritable bowel syndrome and fibromyalgia) is a topic under discussion. In conclusion, the novelty of this matter has generated an expansion of literature data with the unavoidable consequence that some reports are often based on low levels of evidence. Therefore, only studies performed on large samples with the inclusion of control groups will be able to clearly establish whether the large information from the literature regarding extra-intestinal NCGS manifestations could be supported by evidence-based agreements.

Effect of Dietary Supplementation with Hydrolyzed Wheat Gluten on Growth Performance, Cell Immunity and Serum Biochemical Indices of Weaned Piglets (Sus scrofa)

To investigate the effects of dietary supplementation with hydrolyzed wheat gluten （HWG） on growth performance, cell immunity and serum biochemical indices of weaned piglets, 160 crossed （Large White×andrace） and weaned piglets were randomly divided into 4 treatments with 4 replicates of 10 piglets each. The piglets in each treatment were fed an experimental diet containing either 0 g kg-1 HWG （control group）, 30 g kg-1 HWG （3% HWG group）, 50 g kg-1 HWG （5% HWG group）, or 2.5 g kg-1 glycyl-L-glutamine （0.25% Gly-Gln group）. The results showed that the diarrhea rates in 3% HWG and 5% HWG groups were significantly lower than in control group from d 1 to 14 （P〈0.05）, while the average daily gain （ADG） in each of two groups was increased （P〉0.05）. When compared with control group, dietary supplementation with 3% HWG increased the ratio of CD4＋：CD8＋ and the ratio of serum albumin and globulin concentrations （A：G） on d 14 and 28, as well as the proliferation of T- and B-lymphocytes （P〉0.05） on d 28. In addition, on d 14 and 28, the A：G ratio in 5% HWG group was significantly higher than in control group （P〈0.05）, while the ratio of CD4＋：CD8＋ increased slightly （P〉0.05）. Interestingly, 0.25% Gly-Gln group had higher proportion of CD3＋ （P〉0.05） and CD4＋ （P〈0.05） on d 14 than control group, but growth performances of 0.25% Gly-Gln group were negatively affected at all experiment stages. These results suggested that HWG might improve the growth performance of piglets by strengthening cell immunity and decreasing the occurrence of diarrhea during the prophase after weaning.

Clinical and diagnostic aspects of gluten related disorders

Gluten is one of the most abundant and widely distributed components of food in many areas. It can be included in wheat, barley, rye, and grains such as oats, barley, spelt, kamut, and triticale. Gluten-containinggrains are widely consumed; in particular, wheat is one of the world's primary sources of food, providing up to 50% of the caloric intake in both industrialized and developing countries. Until two decades ago, celiac disease(CD) and other gluten-related disorders were believed to be exceedingly rare outside of Europe and were relatively ignored by health professionals and the global media. In recent years, however, the discovery of important diagnostic and pathogenic milestones led CD from obscurity to global prominence. In addition, interestingly, people feeding themselves with glutenfree products greatly outnumber patients affected by CD, fuelling a global consumption of gluten-free foods with approximately $2.5 billion in United States sales each year. The acknowledgment of other medical conditions related to gluten that has arisen as health problems, providing a wide spectrum of gluten-related disorders. In February 2011, a new nomenclature for gluten-related disorders was created at a consensus conference in London. In this review, we analyse innovations in the field of research that emerged after the creation of the new classification, with particular attention to the new European Society for Paediatric Gastroenterology, Hepatology and Nutrition guidelines for CD and the most recent research about non-celiac gluten sensitivity.

Conditional and unconditional QTLs mapping of gluten strength in common wheat (Triticum aestivum L.)

Dissecting the genetic relationships among gluten-related traits is important for high quality wheat breeding. Quantita- tive trait loci （QTLs） analysis for gluten strength, as measured by sedimentation volume （SV） and gluten index （GI）, was performed using the QTLNetwork 2.0 software. Recombinant inbred lines （RILs） derived from the winter wheat varieties Shannong 01-35xGaocheng 9411 were used for the study. A total of seven additive QTLs for gluten strength were identi- fied using an unconditional analysis. QGi1D-13 and QSv1D-14 were detected through unconditional and conditional QTLs mapping, which explained 9.15-45.08% of the phenotypic variation. QTLs only identified under conditional QTL mapping were located in three marker intervals： WPT-3743-GLU-D1 （1D）, WPT-7001-WMC258 （1B）, and WPT-8682-WPT-5562 （1B）. Six pairs of epistatic QTLs distributed nine chromosomes were identified. Of these, two main effect QTLs （QGi1D-13 and QSvlD-14） and 12 pairs of epistatic QTLs were involved in interactions with the environment. The results indicated that chromosomes 1B and 1D are important for the improvement of gluten strength in common wheat. The combination of conditional and unconditional QTLs mapping could be useful for a better understanding of the interdependence of different traits at the QTL molecular level.

Consumption of gluten with gluten-degrading enzyme by celiac patients: A pilot-study

AIM:To assesses the safety and efficacy of Aspergillus niger prolyl endoprotease(AN-PEP)to mitigate the im-munogenic effects of gluten in celiac patients.METHODS:Patients with initial diagnosis of celiac disease as confirmed by positive serology with subtotal or total villous atrophy on duodenal biopsies who adhere to a strict gluten-free diet(GFD)resulting in normalised antibodies and mucosal healing classified as Marsh 0 orⅠwere included.In a randomised double-blind placebo-controlled pilot study,patients consumed toast(approximately 7 g/d gluten)with AN-PEP for 2 wk(safety phase).After a 2-wk washout period with adherence of the usual GFD,14 patients were randomised to gluten intake with either AN-PEP or placebo for 2 wk(efficacy phase).Measurements at baseline included complaints,quality-of-life,serum antibodies,immunophenotyping of T-cells and duodenal mucosa immunohistology.Furthermore,serum and quality of life questionnaires were collected during and after the safety,washout and efficacy phase.Duodenal biopsies were collected after the safety phase and after the efficacy phase.A change in histological evaluation according to the modified Marsh classification was the primary endpoint.RESULTS:In total,16 adults were enrolled in the study.No serious adverse events occurred during the trial and no patients withdrew during the trial.The mean score for the gastrointestinal subcategory of the celiac disease quality(CDQ)was relatively high throughout the study,indicating that AN-PEP was well tolerated.In the efficacy phase,the CDQ scores of patients consuming gluten with placebo or gluten with AN-PEP did not significantly deteriorate and moreover no differences between the groups were observed.During the efficacy phase,neither the placebo nor the AN-PEP group developed significant antibody titers.The IgA-EM concentrations remained negative in both groups.Two patients were excluded from entering the efficacy phase as their mucosa showed an increase oftwo Marsh steps after the safety phase,yet with undetectable serum antibodies,while 14 patients were considered histologically stable on gluten with AN-PEP.Also after the efficacy phase,no significant deterioration was observed regarding immunohistological and flow cytometric evaluation in the group consuming placebo compared to the group receiving AN-PEP.Furthermore,IgA-tTG deposit staining increased after 2 wk of gluten compared to baseline in four out of seven patients on placebo.In the seven patients receiving AN-PEP,one patient showed increased and one showed decreased IgA-tTG deposits.CONCLUSION:AN-PEP appears to be well tolerated.However,the primary endpoint was not met due to lack of clinical deterioration upon placebo,impeding an effect of AN-PEP.

Effects of Dietary Corn Gluten Meal on Growth Performance and Protein Metabolism in Relation to IGF-I and TOR Gene Expression of Juvenile Cobia (Rachycentron canadum)

A growth experiment was conducted on cobia(Rachycentron canadum,initial weight 108.2 g ± 3.0 g) to investigate the effects of dietary corn gluten meal(CGM) levels on the fish growth,whole body composition and protein metabolism in relation to specific gene expression.Five isonitrogenous(crude protein 45%) and isoenergetic(gross energy 20 kJ g 1) practical diets were formulated by replacing 0%(the control),17.5%,35.0%,52.5%,and 70.0% of fish meal(FM) protein with CGM protein.No significant differences were observed in the survival,feed intake(FI),specific growth rate(SGR),feed efficiency(FE) and protein productive value(PPV) among fish fed diets with 0%,17.5%,35.0%,and 52.5% of CGM protein.However,these indices were significantly lower in fish fed the diet with 70.0% of CGM protein than those in fish fed the control diet(P < 0.05).The whole-body crude protein and lipid contents were significantly lower while the whole-body moisture content was significantly higher in fish fed the diet with 70.0% of CGM protein compared with the control group(P < 0.05).When 70.0% of FM protein was replaced by CGM,plasma total protein and cholesterol contents were significantly lower than those in the control group(P < 0.05).Fish fed the diet with 70.0% of CGM protein had significantly lower hepatic insulin-like growth factor I(IGF-I) expression levels than those in the control group(P < 0.05).However,no significant differences were observed in hepatic target of rapamycin(TOR),dorsal muscle IGF-I and TOR expression levels among dietary treatments.Results of the present study indicated that 52.5% of FM protein could be replaced by CGM in the diets without significant influences on the growth,feed utilization and protein metabolism of juvenile cobia.The present results might be useful for developing cost effective and sustainable cobia dietary formulations.

Gluten immunogenic peptide excretion detects dietary transgressions in treated celiac disease patients

BACKGROUND Life-long removal of gluten from the diet is currently the only way to manage celiac disease(CeD). Until now, no objective test has proven useful to objectively detect ingested gluten in clinical practice. Recently, tests that determine consumption of gluten by assessing excretion of gluten immunogenic peptides(GIP) in stool and urine have been developed. Their utility, in comparison with conventional dietary and analytical follow-up strategies, has not been fully established.AIM To assess the performance of enzyme-linked immunosorbent assay(ELISA) and point-of-care tests(PoCTs) for GIP excretion in CeD patients on gluten-free diet(GFD).METHODS We conducted an observational, prospective, cross-sectional study in patients following a GFD for at least two years. Using the Gastrointestinal Symptom Rating Scale questionnaire, patients were classified at enrollment as asymptomatic or symptomatic. Gluten consumption was assessed twice by 3-d dietary recall and GIP excretion(by ELISA in stool and PoCTs(commercial kits for stool and urine) in two consecutive samples. These samples and dietary reports were obtained 10 day apart one from the other. Patients were encouraged to follow their usual GFD during the study period.RESULTS Forty-four patients were enrolled, of which 19(43.2%) were symptomatic despite being on a GFD. Overall, 83 sets of stool and/or urine samples were collected.Eleven out of 44 patients(25.0%) had at least one positive GIP test. The occurrence of at least one positive test was 32% in asymptomatic patients compared with 15.8% in symptomatic patients. GIP was concordant with dietary reports in 65.9% of cases(Cohen′s kappa: 0.317). PoCT detected dietary indiscretions. Both ELISA and PoCT in stool were concordant(concomitantly positive or negative) in 67 out of 74(90.5%) samples. Excretion of GIP was detected in 7(8.4%) stool and/or urine samples from patients considered to be strictly compliant with the GFD by dietary reports.CONCLUSION GIP detects dietary transgressions in patients on long-term GFD, irrespective of the presence of symptoms. PoCT for GIP detection constitutes a simple homebased method for self-assessment of dietary indiscretions.

Celiac disease: Alternatives to a gluten free diet

Celiac disease is a chronic inflammatory disorder of the small intestine caused by the ingestion of gluten or related rye and barley proteins. At present, the only available treatment is a strict gluten-exclusion diet. However, recent understanding of the molecular basis for this disorder has improved and enabled the identif ication of targets for new therapies. This article aims to critically summarize these recent studies.

Effect of the timing of gluten introduction on the development of celiac disease

Celiac disease(CD) is a permanent auto-immune enteropathy,triggered in genetically predisposed individuals by the ingestion of dietary gluten.Gluten is the alcohol-soluble protein component of the cereals wheat,rye and barley.CD is a multifactorial condition,originating from the interplay of genetic and environmental factors.The necessary environmental trigger is gluten,while the genetic predisposition has been identified in the major histocompatibility complex region on chromosome 6p21,with over 90% of CD patients expressing HLA DQ2 and the remaining celiac patients express DQ8.The fact that only about 4% of DQ2/8positive individuals exposed to gluten develop CD,has led to the recognition that other genetic and environmental factors are also necessary.In the last few years,several epidemiological studies have suggested that the timing of the introduction of gluten,as well as the pattern of breastfeeding,may play an important role in the subsequent development of CD.Here,we present and review the most recent evidences regarding the effect of timing of gluten introduction during weaning,the amount of gluten introduced and simultaneous breastfeeding,on the development of CD.

Non-celiac gluten sensitivity:Time for sifting the grain

In the last few years, a new nomenclature has been proposed for the disease induced by the ingestion of gluten, a protein present in wheat, rice, barley and oats. Besides celiac disease and wheat allergy, the most studied forms of gluten-related disorders characterized by an evident immune mechanism(autoimmune in celiac disease and Ig E-mediated in wheat allergy), a new entity has been included, apparently not driven by an aberrant immune response: the non-celiac gluten sensitivity(NCGS). NCGS is characterized by a heterogeneous clinical picture with intestinal and extraintestinal symptoms arising after gluten ingestion and rapidly improving after its withdrawal from the diet. The pathogenesis of NCGS is largely unknown, but a mixture of factors such as the stimulation of the innate immune system, the direct cytotoxic effects of gluten, and probably the synergy with other wheat molecules, are clues for the complicated puzzle. In addition, the diagnostic procedures still remain problematic due to the absence of efficient diagnostic markers; thus, diagnosis is based upon the symptomatic response to a gluten-free diet and the recurrence of symptoms after gluten reintroduction with the possibility of an important involvement of a placebo effect. The temporary withdrawal of gluten seems a reasonable therapy, but the timing of gluten reintroduction and the correct patient management approach are have not yet been determined.