Utilizing Telemedicine Applications in Celiac Disease and Other Gluten-Free-Diet-Dependent Conditions: Insights from the COVID-19 Pandemic.

BACKGROUND: Globally, approximately 1.4% of people have celiac disease (CD), induced by gluten sensitivity. If left untreated, it causes small intestinal inflammation and villous atrophy, which can result in failure to thrive, anemia, osteoporosis, malabsorption, and even malignancy. The only treatment option available is a gluten-free diet (GFD). Few studies have looked at the role and perception of telehealth in relation to CD and selective nutrition both before and after the COVID-19 pandemic. AIM: Our goal was to screen and investigate the research conducted both before and after the COVID-19 pandemic concerning the utilization of telehealth applications and solutions in CD and other GFD-dependent circumstances. METHODS: We employed a narrative review approach to explore articles that were published in scholarly journals or organizations between the years 2000 and 2024. Only English-language publications were included. PubMed and Google Scholar searches were mainly conducted using the following keywords: telemedicine, telehealth, telecare, eHealth, m-health, COVID-19, SARS-CoV-2, celiac disease, and gluten-free diet (GFD). Manual searches of the references in the acquired literature were also carried out, along with the authors' own personal contributions of their knowledge and proficiency in this field. RESULTS: Only a few studies conducted prior to the COVID-19 outbreak examined the viewpoints and experiences of adult patients with CD with relation to in-person clinic visits, as well as other options such as telehealth. The majority of patients believed that phone consultations were appropriate and beneficial. Video conferencing and telemedicine became more popular during the COVID-19 pandemic, demonstrating the effectiveness of using these technologies for CD on a global basis. In recent years, urine assays for gluten identification have become accessible for use at home. These tests could be helpful for CD monitoring with telemedicine assistance. CONCLUSIONS: The extended knowledge gathered from the COVID-19 pandemic is expected to complement pre-COVID-19 data supporting the usefulness of telemedicine even after the emergent pandemic, encouraging its wider adoption in standard clinical practice. The monitoring and follow-up of CD patients and other GFD-dependent conditions can greatly benefit from telemedicine.

Peasant vs. Industrial durum wheat pasta: Impact of each processing step on protein solubility and digestibility.

Some people with Non-Coeliac Gluten (or Wheat) Sensitivity (NCGS) declare that they can consume peasant pasta without the usual inconvenience they experience after eating industrial pasta. The main differences between peasant and industrial pasta lie in the varieties used (old vs. modern), and the production chain (grain milling, semolina hydration and mixing, extrusion or lamination, drying and packaging). Yet, the varieties, the material and the method used by the peasants and by the industrial sector to make pasta differ at each stage. The impact of each of these stages was analyzed on protein quantity and quality from semolina to cooked pasta. Grown in the same conditions, the old variety (cv. Bidi 17) used by farmers contained much more protein than the modern variety (cv. Anvergur) recommended by industry and its pasta was better-digested in-vitro. Focusing on cooked pasta, milling had a great impact on not easily soluble proteins (DTE-soluble proteins): pasta made from stone-milled grains (peasant method) had less DTE-soluble proteins than pasta made from roller-milled grains (industrial method) and a higher amount of in-vitro digested proteins. The mixing and extrusion step mainly affected the easily soluble proteins (SDS-soluble proteins). The amount of such proteins was greater for farmer cooked pasta (non-monitored extrusion) than for industrial ones (monitored extrusion). Concerning the drying step, the proportion of SDS-soluble proteins was higher for the pasta dried at low temperature (peasant method), compared to high temperature (industrial method). Thus, the observation that peasant cooked pasta would be more digestible than industrial pasta seems to be due mainly to variety (61%), to a lesser extent to grinding on a stone-mill (22%) and extrusion on non-monitored conditions (16%) and finally a little (1%) to drying at low temperature and therefore longer.

Home-Based Double-Blind, Placebo-Controlled Challenges for Diagnosis of Delayed Gluten/Milk Hypersensitivity in Children.

BACKGROUND: Delayed hypersensitivity to gluten and milk protein is frequently reported but may be difficult to diagnose. OBJECTIVE: We aimed to explore if a method of home-based double-blind placebo-controlled food challenges (H-FC) can identify and reduce unnecessary elimination diets in children. METHODS: We included 73 of 92 children aged 1 to 17 years referred to a tertiary allergy clinic from 2011 to 2021 due to self-reported, delayed symptoms to gluten or milk. The children were randomized to H-FC, receiving gluten/milk protein or placebo for 5 to 7 days in a double-blind crossover manner, separated by 3 washout weeks. Patients/parents recorded symptoms using standardized forms. Two crossover periods were used from 2011 to 2016 and 3 periods from 2017 to 2021. A positive challenge required significantly more symptoms during the active period versus the placebo period. After the challenge, reintroduction of milk/gluten was assessed by a follow-up interview. The primary outcome was the proportion of children with a positive challenge. RESULTS: The children, with a mean age of 11 years, had followed a strict gluten-free or milk-protein-free diet for a median duration of 24 months (range: 3-180 months). A positive challenge was observed in 18 of 73 children (25%), more often using 2 (35%) compared with 3 challenge periods (12%). At follow-up, 44 of 55 (80%) children with a negative challenge had successfully reintroduced milk/gluten. CONCLUSIONS: H-FC may be an effective method in avoiding unnecessary elimination diets in children. Only 25% of the challenges were positive, and 80% of the children with negative challenges succeeded in reintroducing the food. Three challenge periods may be necessary to reduce false-positive outcomes.

A method to investigate sterilization processes and the bacterial inactivation resolved in time and space.

In this study, a Computational Fluid Dynamics (CFD) model was developed to predict all relevant phenomena occurring during a moist heat sterilization process at a high level of temporal and spatial resolution. The developed CFD model was used to simulate the distribution of, e.g., pressure, temperature and residual air within a large-scale industrial steam autoclave (multiphase flow models) which was not published until now. Moreover, the thermodynamic behavior and distribution of fluids and temperatures inside the sterilization load was simulated which were verified with measurements. Based on the obtained sterilization temperature profiles in connection with the sterilization environment (e.g., NCGs, natural convection), the bacterial inactivation could be simulated. A complete moist heat sterilization process was simulated, including all relevant phenomena inside an autoclave chamber and a Peritoneal Dialysis Bag System (PDBS), which represents a complex sterilization item. To verify the simulation results, simulated pressures and temperatures were compared with measurement data for both the autoclave chamber and the PDBS. The results show that the simulated and measured values were in excellent accordance. By using the novel CFD model, the distribution of steam and residual air inside the autoclave chamber, as well as the natural convection inside the sterilization load, could be precisely predicted. To predict the inactivation of Geobacillus stearothermophilus inside different moist heat environments, the CFD model was extended with bacterial inactivation kinetics based on measurement data. The simulation results clearly indicate that our developed CFD model can be used to predict the inactivation kinetics of bacteria, depending on the sterilization temperature profile of the sterilization process as well as the moist heat sterilization environment, and to resolve the kinetics in time and space. Therefore, the developed CFD model represents a powerful tool that might be used in the future to predict, e.g., ″worst case″ locations for any given autoclave and sterilization load or any other relevant process parameter, enabling the operator to develop an effective sterilization process.

Gluten Sensitivity Underlying Resistant "Laryngopharyngeal Reflux" Symptoms and Signs.

INTRODUCTION: Laryngopharyngeal reflux (LPR) is one of the most common conditions encountered in otolaryngology. Gluten sensitivity may mimic the signs and symptoms of LPR or act as an aggravating cofactor with LPR. Gluten sensitivity and food intolerance also have been implicated as conditions that may be associated specifically with LPR symptoms and signs resistant to traditional medical treatment. Medical management of LPR may be insufficient to control symptoms and laryngeal signs of reflux, constituting resistant LPR. Eliminating gluten from the diet could provide symptomatic relief to patients with gluten sensitivity and LPR that is not controlled adequately by current regimens. The purpose of our study was to investigate the relationship between gluten sensitivity and LPR. We aimed to evaluate reflux finding score (RFS) improvement following elimination of gluten from the diet in patients with resistant LPR who had positive blood tests associated with gluten sensitivity. Symptom improvement was also assessed following dietary gluten elimination. Lastly, we aimed to identify predictors for a positive response to a gluten-free diet. METHODS: Adult patients who underwent gluten sensitivity testing for treatment-resistant LPR symptoms and/or signs were included. Patients with ≥1 positive test were advised to begin a therapeutic trial of a gluten-free diet. Subjects who chose not to trial a gluten-free diet or tested negative for gluten sensitivity markers served as controls. RFS was the primary outcome measure. RESULTS: One hundred ninety-seven patients were included; 81 trialed a gluten-free diet. Subjects who trialed the gluten-free diet were significantly more likely to demonstrate objective improvement in RFS (77.14% vs 43.88%), and report subjective improvement (55.41% vs 25.77%) than those who did not. RFS had decreased significantly from baseline at 1-3, 3-6, 6-12, and >12-month interval follow-up examinations in subjects who trialed a gluten-free diet. Comparison between subjects who trialed the gluten-free diet, tested positive for a gluten sensitivity marker but did not trial the gluten-free diet, and subjects who were negative for all gluten sensitivity markers revealed that a gluten-free diet was associated with a significantly greater percent improvement in RFS compared to controls at 1-3, 6-12, and >12-months. CONCLUSION: Gluten sensitivity can mimic or aggravate LPR. A gluten-free diet should be considered for patients with resistant LPR, especially if blood test abnormalities that suggest gluten sensitivity are identified. The diet should be maintained for a minimum of three months to demonstrate objective improvement using RFS.

New Insights and Evidence on "Food Intolerances": Non-Celiac Gluten Sensitivity and Nickel Allergic Contact Mucositis.

The clinical examination of patients often includes the observation of the existence of a close relationship between the ingestion of certain foods and the appearance of various symptoms. Until now, the occurrence of these events has been loosely defined as food intolerance. Instead, these conditions should be more properly defined as adverse food reactions (AFRs), which can consist of the presentation of a wide variety of symptoms which are commonly identified as irritable bowel syndrome (IBS). In addition, systemic manifestations such as neurological, dermatological, joint, and respiratory disorders may also occur in affected patients. Although the etiology and pathogenesis of some of them are already known, others, such as non-celiac gluten sensitivity and adverse reactions to nickel-containing foods, are not yet fully defined. The study aimed to evaluate the relationship between the ingestion of some foods and the appearance of some symptoms and clinical improvements and detectable immunohistochemical alterations after a specific exclusion diet. One hundred and six consecutive patients suffering from meteorism, dyspepsia, and nausea following the ingestion of foods containing gluten or nickel were subjected to the GSRS questionnaire which was modified according to the "Salerno experts' criteria". All patients underwent detection of IgA antibodies to tissue transglutaminase, oral mucosal patch tests with gluten and nickel (OMPT), and EGDS, including biopsies. Our data show that GSRS and OMPT, the use of APERIO CS2 software, and the endothelial marker CD34 could be suggested as useful tools in the diagnostic procedure of these new pathologies. Larger, multi-center clinical trials could be helpful in defining these emerging clinical problems.

Improving parametric load release for steam sterilization.

BACKGROUND: Current standards and procedures for parametric load release are based on technologies from the 1960s, are consensus based and are often not supported by scientific evidence. In the literature, however, methods are reported which can fairly easily be implemented and improve current parametric load release for steam sterilization. AIM: To implement an improved parametric load release procedure, exceeding the current standards and methods for monitoring steam sterilization processes. Implementation of the procedure should be feasible for all interested end-users. METHOD: The steam sterilization criteria specified in the literature were used to define a set of steam sterilization conditions. A search for commercially available devices and methods which can assess these conditions parametrically was performed. After selecting a method, a field study was carried out. FINDINGS: Two devices were identified which could be used to improve parametric load release after a steam sterilization process. A comparison showed that a permanently installed device which - independent from the sterilizer - measures the temperature, the steam composition in the chamber and the time for every steam sterilization process, offers the most advantages. The selected method has been implemented and tested on 51 steam sterilizers. CONCLUSION: The selected method makes steam sterilization safer, more sustainable, and more cost effective. It can be implemented by all interested end-users.

The conformation of glutenin polymers in wheat grain: some genetic and environmental factors associated with this important characteristic.

In a previous study we used asymmetric-flow field-flow fractionation to determine the polymer mass (Mw), gyration radius (Rw) and the polydispersity index of glutenin polymers (GPs) in wheat (Triticum aestivum). Here, using the same multi-location trials (4 years, 11 locations, and 192 cultivars), we report the factors that are associated with the conformation (Conf) of the polymers, which is the slope of Log(Rw) versus a function of Log(Mw). We found that Conf varied between 0.285 and 0.740, it had low broad-sense heritability (H2=16.8), and it was significantly influenced by the temperature occurring over the last month of grain filling. Higher temperatures were found to increase Rw and the compactness and sphericity of GPs. Alleles for both high- and low-molecular-weight glutenin subunits had a significant influence on the Conf value. Assuming a Gaussian distribution for Mw, the number of polymers present in wheat grains was computed for different kernel weights and protein concentrations, and it was found to exceed 1012 GPs per grain. Using atomic force microscopy and cryo-TEM, images of GPs were obtained for the first time. Under higher average temperature, GPs became larger and more spherical and consequently less prone to rapid hydrolysis. We propose some orientations that could be aimed at potentially reducing the impact of numerous GPs on people suffering from non-celiac gluten sensitivity.

Digestion of protein and toxic gluten peptides in wheat bread, pasta and cereal and the effect of a supplemental enzyme mix.

There has been an increasing interest in the relationship between wheat digestibility and potential toxicity to the host. However, there is a lack of understanding about temporal profile of digestion of wheat proteins from different food matrices under physiologically relevant conditions. In this study, digestion of three wheat-based foods (bread, pasta and cereal) was conducted based on the INFOGEST semi-dynamic protocol in the absence and presence of a commercial supplemental enzyme preparation (a Glutalytic® based supplement, which will be marketed as Elevase®). Protein hydrolysis (OPA- ortho-phthalaldehyde - assay), molecular weight distribution (SEC-HPLC) and potential toxicity (R5 antibody-based competitive ELISA), were assessed. Our results demonstrated that under normal conditions, the complexity of the food influenced the temporal profile of protein hydrolysis and gluten breakdown throughout simulated gastric and intestinal digestion. However, treatment with the enzyme supplement significantly and acutely increased protein hydrolysis and gluten degradation in the gastric stage, and this enhanced digestion was maintained into the intestinal environment. These findings highlight the limitations of temporal gastric proteolysis and gluten degradation under normal conditions to different food types. They also show that supplemental enzyme mixes can effectively accelerate the breakdown of protein and hydrolysis of toxic gliadin fractions from the early stages of gastric digestion, thereby reducing intestinal exposure and potentially limiting the sensitization of the host.

Non-Celiac Gluten Sensitivity and Protective Role of Dietary Polyphenols.

Pathogenetically characterized by the absence of celiac disease and wheat allergy, non-celiac gluten sensitivity (NCGS) is a clinical entity triggered by the consumption of gluten-containing foods that relieved by a gluten-free diet. Since it is very difficult to maintain a complete gluten-free diet, there is a high interest in discovering alternative strategies aimed at reducing gluten concentration or mitigating its toxic effects. Plant-based dietary models are usually rich in bioactive compounds, such as polyphenols, recognized to prevent, delay, or even reverse chronic diseases, including intestinal disorders. However, research on the role of polyphenols in mitigating the toxicity of gluten-containing foods is currently limited. We address the metabolic fate of dietary polyphenols, both as free and bound macromolecule-linked forms, with particular reference to the gastrointestinal compartment, where the concentration of polyphenols can reach high levels. We analyze the potential targets of polyphenols including the gluten peptide bioavailability, the dysfunction of the intestinal epithelial barrier, intestinal immune response, oxidative stress and inflammation, and dysbiosis. Overall, this review provides an updated overview of the effects of polyphenols as possible dietary strategies to counteract the toxic effects of gluten, potentially resulting in the improved quality of life of patients with gluten-related disorders.

Monolayer PC3: A promising material for environmentally toxic nitrogen-containing multi gases.

Carbon and its analogous nanomaterials are beneficial for toxic gas sensors since they are used to increase the electrochemically active surface region and improve the transmission of electrons. The present article addresses a detailed investigation on the potential of the monolayer PC3 compound as a possible sensor material for environmentally toxic nitrogen-containing gases (NCGs), namely NH3, NO, and NO2. The entire work is carried out under the frameworks of density functional theory, ab-initio molecular dynamics simulations, and non-equilibrium Green's function approaches. The monolayer-gas interactions are studied with the van der Waals dispersion correction. The stability of pristine monolayer PC3 is confirmed through dynamical, mechanical, and thermal analyses. The mobility and relaxation time of 2D PC3 sensor material with NCGs are obtained in the range of 101-104 cm2 V-1 s-1 and 101-103 fs for armchair and zigzag directions, respectively. Out of six possible adsorption sites for toxic gases on the PC3 surface, the most prominent site is identified with the highest adsorption energy for all the NCGs. Considering the most stable configuration site of the NCGs, we have obtained relevant electronic properties by utilizing the band unfolding technique. The considerable adsorption energies are obtained for NO and NO2 compared to NH3. Although physisorption is observed for all the NCGs on the PC3 surface, NO2 is found to convert into NO and O at 5.05 ps (at 300 K) under molecular dynamics simulation. The maximum charge transfer (0.31e) and work function (5.17 eV) are observed for the NO2 gas molecule in the series. Along with the considerable adsorption energies for NO and NO2 gas molecules, their shorter recovery time (0.071 s and 0.037 s, respectively) from the PC3 surface also identifies 2D PC3 as a promising sensor material for those environmentally toxic gases. The experimental viability and actual implications for PC3 monolayer as NCGs sensor material are also confirmed by examining the humidity effect and transport properties with modeled sensor devices. The transport properties (I-V characteristics) reflect the significant sensitivity of PC3 monolayer toward NO and NO2 molecules. These results certainly confirm PC3 monolayer as a promising sensor material for NO and NO2 NCG molecules.

Development of an instrument to measure perceived gentrification for health research: Perceptions about changes in environments and residents (PACER).

Despite a myriad of potential pathways linking neighborhood change and gentrification to health, existing quantitative measures failed to capture individual-level, self-reported perceptions of these processes. We developed the Perceptions About Change in Environment and Residents (PACER) survey to measure the gentrification-related neighborhood change experienced by individuals relevant to health. We employed a multi-stage process to develop PACER including a scoping review, question refinement, content validity, and cognitive interviews. Content validity and cognitive interviews were assessed within the National Neighborhood Indicators Partnership (NNIP) and for residents of different tenure in both gentrifying and non-gentrifying neighborhoods to ensure PACER considers the complex nature of neighborhood change for different people within different urban contexts. We piloted the instrument to a sample from the resident panel BeHeardPhilly to assess acceptability and data quality. Finally, we assessed internal consistency, dimensionality, and criterion-related validity using Principal Components Analysis (PCA), descriptive statistics, and correlation coefficients. Testing showed good internal consistency for PACER questions, as well as for each of four resulting factors (Feelings, Built Environment, Social Environment, and Affordability). Correlations between factors and other context measures demonstrated strong criterion-related validity. PACER offers an unprecedented tool for measuring and understanding resident perceptions about gentrification-related neighborhood change relevant to health. Rigorously tested and tailored for health, PACER holds utility for application across different settings to examine changes from events that may impact and shift neighborhoods.

Non-Celiac Gluten Sensitivity: An Update.

Non-celiac gluten sensitivity (NCGS) is a clinical entity characterized by the absence of celiac disease and wheat allergy in patients that trigger reproducible symptomatic responses to gluten-containing foods consumption. Due to the lack of sensitive and reproducible biomarkers for NCGS diagnosis, placebo-controlled gluten challenges must be carried out for its diagnosis. The gluten challenges can be either double- or single-blind, for research or clinical practice purposes, respectively. For improving our understanding about the magnitude and relevance of NCGS in different populations, epidemiological studies based on self-report have been carried out. However, the gluten challenge-based prevalence of NCGS remains to be estimated. Since NCGS was recently recognized as a clinical entity, more studies are needed to delve into NCGS pathogenesis, for instance, the molecular interactions between the suspected cereal grain components that trigger NCGS, such as fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs) and amylase and trypsin inhibitors, and the immune system remains to be elucidated. Although still under debate, NCGS patients can be susceptible to only one or more than one of the NCGS triggers. The treatment of NCGS involves the dietary restriction of the suspected triggers of the disease, but there is controversial data about the effectiveness of different dietary interventions such as the gluten-free diet and low-FODMAP diet. Certainly, our understanding of NCGS is improving quickly due to the constant availability of new scientific information on this topic. Thus, the aim of the present narrative review is to present an up-to-date overview on NCGS from epidemiology to current therapy.

An algorithm for differentiating food antigen-related gastrointestinal symptoms.

AIM: The aim of this clinical audit was to assess patient-reported outcomes on the effect of dietary intervention, to enhance our understanding of possible treatment options in irritable bowel syndrome (IBS). BACKGROUND: A large number of food-related gastro-intestinal disorders have been attributed to IBS for decades. METHODS: Patient-reported outcomes from the records of 149 IBS patients treated at secondary and tertiary Gastroenterology outpatients in two UK hospitals between January 2014 and July 2016 were audited. Patients all presented with symptoms fulfilling Rome III-IV criteria for IBS had negative coeliac serology and did not have other gastrointestinal (GI) conditions. A modified version of a low FODMAP diet had been recommended (gluten and lactose free diet (G/LFD)) and was implemented for 6 weeks. Outcomes and dietary adherence were recorded during outpatient's consultations. RESULTS: A total of 134 patients complied with the diet optimally. The majority had an improvement rate >70% and continued with the diet. Fifty-three percent became completely or almost asymptomatic, while 27.6% had a poor response to the diet (scoring < 30%) to G/LFD. The improvement was excellent in patients with normal BMI and good in overweight and obese and where BMI <18. Over 50% did not require any follow-up within 12 months. CONCLUSION: Although it is unclear whether symptoms are triggered by gluten, fructans or lactose, elimination of gluten and lactose proved to be an effective treatment in patients with IBS. Multidisciplinary team management and implementation of detailed nutrition therapy using the audit algorithm might prove to be both cost effective and efficacious a treatment option in IBS.

Hierarchical fabrication of hollow Co2P nanocages coated with ZnIn2S4 thin layer: Highly efficient noble-metal-free photocatalyst for hydrogen evolution.

The directional synthesis of transition metal phosphides was considered to be an effective strategy to solve the overdependence of noble metals on photocatalytic hydrogen evolution (PHE) reactions. Inspiringly, this work reported a facile method for constructing hollow Co2P nanocages (Co2P NCGs) that derived from ZIF-67 by calcining and phosphiding procedure in nitrogen atmosphere to act as non-noble metal cocatalysts. Followed with further coating thin-layered ZnIn2S4 (ZIS) on the surface of Co2P NCGs through a hydrothermal reaction, the hierarchical robust Co2P/ZnIn2S4 nanocages (Co2P/ZIS NCGs) were then delicately fabricated as efficient photocatalysts for PHE reactions. The uniquely hollow structure of Co2P NCGs largely diffused the photogenerated chargers that induced from ZIS and the closely interfacial contact significantly promoted the separation and transfer of electrons from ZIS to Co2P according to density functional theory (DFT) calculation, synergistically resulting in an efficient hydrogen generation performance. PHE results showed that an efficient H2 evolution rate of 7.93 mmol/g/h over 10% Co2P/ZIS NCGs was achieved, about 10 times higher than that of pristine ZnIn2S4. More importantly, the hierarchically hollow Co2P/ZIS NCGs exhibited ascendant PHE activity in comparison with that of 1% noble metal (Pt, Au, Ag) loaded ZnIn2S4 with superior sustainability, all indicating the efficient and stable photocatalysts of Co2P/ZIS NCGs for PHE reactions.

Beyond the HLA Genes in Gluten-Related Disorders.

Most common food grains contain gluten proteins and can cause adverse medical conditions generally known as gluten-related disorders. Celiac disease is an immune-mediated enteropathy triggered by gluten in individuals carrying a specific genetic make-up. The presence of the human leukocyte antigens (HLA)-DQ2 and HLA-DQ8 haplotypes together with gluten intake is a necessary, although not sufficient, condition, to develop celiac disease. Fine mapping of the human genome has revealed numerous genetic variants important in the development of this disease. Most of the genetic variants are small nucleotide polymorphisms located within promoters and transcriptional enhancer sequences. Their importance is underlined by an increased risk in DQ2/DQ8 carriers who also have these non-HLA alleles. In addition, several immune-mediated diseases share susceptibility loci with celiac disease, shedding light on the reasons for co-occurrence between these diseases. Finally, most of the genes potentially involved in celiac disease by fine genetic mapping of non-HLA loci were confirmed in gene expression studies. In contrast to celiac disease, very little is known about the genetic make-up of non-celiac wheat sensitivity (NCWS), a clinically defined pathology that shares symptoms and gluten dependence with the celiac disease. We recently identified differentially expressed genes and miRNAs in the intestinal mucosa of these patients. Remarkably, the differentially expressed genes were long non-coding RNAs possibly involved in the regulation of cell functions. Thus, we can speculate that important aspects of these diseases depend on alteration of regulatory genetic circuits. Furthermore, our finding suggests that innate immune response is involved in the pathogenic mechanism of NCWS. This review is intended to convey the idea that in order to fully understand celiac disease and its relationship with other gluten-related disorders, it is worth learning more about non-HLA variants.

Non-Celiac Gluten Sensitivity in the Context of Functional Gastrointestinal Disorders.

Gluten-free diets are increasingly chosen in the Western world, even in the absence of a diagnosis of celiac disease. Around 10% of people worldwide self-report gluten-related complaints, including intestinal and extra-intestinal symptoms. In most cases, these subjects would be labeled as patients suffering from irritable bowel syndrome (IBS) who place themselves on a gluten-free diet even in the absence of celiac disease. In some instances, patients report a clear benefit by avoiding gluten from their diet and/or symptom worsening upon gluten reintroduction. This clinical entity has been termed non-celiac gluten sensitivity (NCGS). The symptoms referred by these patients are both intestinal and extra-intestinal, suggesting that similarly to functional gastrointestinal disorders, NCGS is a disorder of gut-brain interaction. It remains unclear if gluten is the only wheat component involved in NCGS. The mechanisms underlying symptom generation in NCGS remain to be fully clarified, although in the past few years, the research has significantly moved forward with new data linking NCGS to changes in gut motility, permeability and innate immunity. The diagnosis is largely based on the self-reported reaction to gluten by the patient, as there are no available biomarkers, and confirmatory double-blind challenge protocols are unfeasible in daily clinical practice. Some studies suggest that a small proportion of patients with IBS have an intolerance to gluten. However, the benefits of gluten-free or low-gluten diets in non-celiac disease-related conditions are limited, and the long-term consequences of this practice may include nutritional and gut microbiota unbalance. Here, we summarize the role of gluten in the clinical features, pathophysiology, and management of NCGS and disorders of gut-brain interaction.

The Two Faces of Wheat.

Wheat-based foods have been staple foods since about 10,000 years and constitute a major source of energy, dietary fiber, and micronutrients for the world population. The role of wheat in our diet, however, has recently been scrutinized by pseudoscientific books and media reports promoting the overall impression that wheat consumption makes people sick, stupid, fat, and addicted. Consequently, numerous consumers in Western countries have started to question their dietary habits related to wheat consumption and voluntarily decided to adopt a wheat-free diet without a medical diagnosis of any wheat-related disorder (WRD), such as celiac disease, wheat allergy, or non-celiac gluten sensitivity. The aim of this review is to achieve an objective judgment of the positive aspects of wheat consumption as well as adverse effects for individuals suffering from WRDs. The first part presents wheat constituents and their positive nutritional value, in particular, the consumption of products from whole-grain flours. The second part is focused on WRDs that affect predisposed individuals and can be treated with a gluten-free or -reduced diet. Based on all available scientific knowledge, wheat consumption is safe and healthy for the vast majority of people. There is no scientific evidence to support that the general population would benefit from a wheat-free diet.

Wheat (Triticum aestivum L.) Breeding from 1891 to 2010 Contributed to Increasing Yield and Glutenin Contents but Decreasing Protein and Gliadin Contents.

Epidemiologic studies suggest an increasing prevalence of celiac disease and non-celiac gluten/wheat sensitivity. With wheat proteins being the main triggers, changes in wheat protein composition are discussed as a potential cause. The goals of breeding toward increased yield and resistance might have inadvertently contributed to a higher immunostimulatory potential of modern wheat cultivars compared to old wheat cultivars. Therefore, agronomic characteristics, protein content, and gluten composition of 60 German winter wheat cultivars first registered between 1891 and 2010 grown in 3 years were analyzed. While plant height and spike density decreased over time, yield and harvest index increased. The protein and gliadin contents showed a decreasing trend, whereas glutenin contents increased, but there were no changes in albumin/globulin and gluten contents. Overall, the harvest year had a more significant effect on protein composition than the cultivar. At the protein level, we found no evidence to support an increased immunostimulatory potential of modern winter wheat.