Parylene Double-Layer Coated Screen-Printed Carbon Electrode for Label-Free and Reagentless Capacitive Aptasensing of Gliadin.

Celiac patients are required to strictly adhere to a gluten-free diet because even trace amounts of gluten can damage their small intestine and leading to serious complications. Despite increased awareness, gluten can still be present in products due to cross-contamination or hidden ingredients, making regular monitoring essential. With the goal of guaranteeing food safety for consuming labeled gluten-free products, a capacitive aptasensor was constructed to target gliadin, the main allergic gluten protein for celiac disease. The success of capacitive aptasensing was primarily realized by coating a Parylene double-layer (1000 nm Parylene C at the bottom with 400 nm Parylene AM on top) on the electrode surface to ensure both high insulation quality and abundant reactive amino functionalities. Under the optimal concentration of aptamer (5 µM) used for immobilization, a strong linear relationship exists between the amount of gliadin (0.01-1.0 mg/mL) and the corresponding ΔC response (total capacitance decrease during a 20 min monitoring period after sample introduction), with an R2 of 0.9843. The detection limit is 0.007 mg/mL (S/N > 5), equivalent to 0.014 mg/mL (14 ppm) of gluten content. Spike recovery tests identified this system is free from interferences in corn and cassava flour matrices. The analytical results of 24 commercial wheat flour samples correlated well with a gliadin ELISA assay (R2 = 0.9754). The proposed label-free and reagentless capacitive aptasensor offers advantages of simplicity, cost-effectiveness, ease of production, and speediness, making it a promising tool for verifying products labeled as gluten-free (gluten content <20 ppm).

The link between gluten intake and the risk of cancers.

Gluten is a complex mixture of hundreds of related proteins, with the two major groups being gliadin and glutenin. Gliadin primarily affects the viscosity of dough, while glutenin contributes to its strength. Nowadays, there is evidence suggesting an increase in gluten exposure due to advancements in cereal technology. Consumption of gluten can lead to development of gluten-related disorders (GRDs) in susceptible individuals. Some GRDs have been strongly associated with an increased risk of developing certain types of cancer. Colorectal cancer and lymphoma are among the most commonly reported malignancies associated with GRDs. Dietary factors, including gluten intake, have been recognized as significant modifiable risk factors for the development of digestive system cancers. The present study aimed to collect current information on the effect of gluten on the incidence of cancer in the general population and among GRDs patients. Protein-Protein Interaction (PPI) Network analysis of common genes between celiac disease (CD) and cancer was also conducted.

Glutenin from the Ancient Wheat Progenitor Is Intrinsically Allergenic as It Can Clinically Sensitize Mice for Systemic Anaphylaxis by Activating Th2 Immune Pathway.

Wheat allergy is a major type of food allergy with the potential for life-threatening anaphylactic reactions. Common wheat, Triticum aestivum (hexaploid, AABBDD genome), was developed using tetraploid wheat (AABB genome) and the ancient diploid wheat progenitor (DD genome)-Aegilops tauschii. The potential allergenicity of gluten from ancient diploid wheat is unknown. In this study, using a novel adjuvant-free gluten allergy mouse model, we tested the hypothesis that the glutenin extract from this ancient wheat progenitor will be intrinsically allergenic in this model. The ancient wheat was grown, and wheat berries were used to extract the glutenin for testing. A plant protein-free colony of Balb/c mice was established and used in this study. The intrinsic allergic sensitization potential of the glutenin was determined by measuring IgE response upon transdermal exposure without the use of an adjuvant. Clinical sensitization for eliciting systemic anaphylaxis (SA) was determined by quantifying the hypothermic shock response (HSR) and the mucosal mast cell response (MMCR) upon intraperitoneal injection. Glutenin extract elicited a robust and specific IgE response. Life-threatening SA associated and a significant MMCR were induced by the glutenin challenge. Furthermore, proteomic analysis of the spleen tissue revealed evidence of in vivo Th2 pathway activation. In addition, using a recently published fold-change analysis method, several immune markers positively and negatively associated with SA were identified. These results demonstrate for the first time that the glutenin from the ancient wheat progenitor is intrinsically allergenic, as it has the capacity to elicit clinical sensitization for anaphylaxis via activation of the Th2 pathway in vivo in mice.

Celiac Disease, Gluten-Free Diet and Metabolic Dysfunction-Associated Steatotic Liver Disease.

Celiac disease (CD) is a chronic autoimmune disorder triggered by the ingestion of gluten-containing food by genetically predisposed individuals. Hence, treatment of CD consists of permanent avoidance of wheat, rye, barley, and other gluten-containing foods. Lifelong adherence to a gluten-free diet (GFD) improves the symptoms of CD, but recent evidence suggests it is also associated with a higher risk for hepatic steatosis and the coexistence or emergence of other cardiometabolic risk factors. Moreover, a higher risk for liver steatosis is also reported by some authors as a potential extraintestinal complication of the CD itself. Recent nomenclature changes designate the association between hepatic steatosis and at least one of five cardiometabolic risk factors as metabolic dysfunction-associated steatotic liver disease (MASLD). An extended network of potentially causative factors underlying the association between MAFLD and CD, before and after dietary therapy is implemented, was recently described. The individualized treatment of these patients is less supported by evidence, with most of the current recommendations relying on empiric clinical judgment. This review focuses on the causative associations between CD and hepatic injury, either as an extraintestinal manifestation of CD or a side effect of GFD, also referring to potential therapeutic strategies for these individuals.

Clinical presentation of celiac disease in adult patients: current real-life experience.

BACKGROUND AND AIMS: The clinical presentation of celiac disease (CD) has changed over time with more patients presenting with non-classical symptoms, extra-intestinal manifestations (EIM) or no symptoms. We aimed to investigate the main symptoms/signs leading to the diagnosis of CD in adult patients. As secondary end-point, we evaluated the outcome of gastrointestinal (GI) symptoms following gluten-free diet (GFD). METHODS: All consecutive CD adult patients referring to our University Hospital from September 2022 to February 2024 were included. Clinical data were retrospectively evaluated. RESULTS: 134 patients, 104 females/30 males, median age at diagnosis 35 years, were included. 79 patients reported GI symptoms (i.e., diarrhea, abdominal bloating, dyspepsia) as the main symptom leading to CD diagnosis. In 40 patients, the leading symptom/sign was an EIM (i.e., iron deficiency anemia, infertility/miscarriages, dermatitis, osteoporosis, elevated transaminase levels). Fifteen patients were asymptomatic, being diagnosed because of a positive family history or concomitant autoimmune hypothyroidism. Of the 79 patients reporting GI symptoms, 20 did not experience complete resolution with the GFD. Among the 17 patients who reported a strict adherence to GFD (vs 1 patient with low-adherence, 2 non-compliant), lactose intolerance and irritable bowel syndrome overlap were diagnosed in 2 and 15 patients, respectively. CONCLUSION: GI manifestations remain the main symptoms at presentation of CD, however clinicians should be aware of the EIM of CD and the association with other autoimmune disorders. In non-responsive CD patients, an overlap with functional disorders might be considered.

Aspergillus niger prolyl endopeptidase in celiac disease.

We comment here on the article by Stefanolo et al entitled "Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet", published in the World Journal of Gastroenterology. Celiac disease is a well-recognized systemic autoimmune disorder. In genetically susceptible people, the most evident damage is located in the small intestine, and is caused and worsened by the ingestion of gluten. For that reason, celiac patients adopt a gluten-free diet (GFD), but it has some limitations, and it does not prevent re-exposure to gluten. Research aims to develop adjuvant therapies, and one of the most studied alternatives is supplementation with Aspergillus niger prolyl endopeptidase protease (AN-PEP), which is able to degrade gluten in the stomach, reducing its concentration in the small intestine. The study found a high adherence to the GFD, but did not address AN-PEP as a gluten immunogenic peptide reducer, as it was only tested in patients following a GFD and not in gluten-exposing conditions. This study opens up new research perspectives in this area and shows that further study is needed to clarify the points that are still in doubt.

Decreasing incidence of celiac disease in Southern Sweden.

BACKGROUND: The incidence of celiac disease (CD) has increased rapidly in the late 20th and early 21st centuries, but there are recent reports of rates levelling off in countries with a high prevalence. The aim of this study was to investigate current trends in CD in southern Sweden. PATIENTS AND METHODS: Children and adults diagnosed with CD by biopsy or serology in the region of Skåne, southern Sweden, from 2010-2022 were included. The home address was identified through registers to analyze temporal and geographical trends. RESULTS: A total of 3218 CD-patients were identified (52.2% children), the vast majority detected in clinical care but a few children by screening studies. The age-standardized incidence rate was 18.6 cases/105. The incidence decreased at a rate of -0.75 cases/105 (95% CI -1.14 to -0.35, p 0.002). The incidence among girls under 18 years almost halved throughout the study period, decreasing by -2.94 cases/105 (95% CI -4.59 to -1.29, p 0.002), while there only were small changes among men. The most common age of onset was 3-9 years. CD incidence varied by place of living and was more common in small towns than urban or rural areas. CONCLUSIONS: The incidence of CD in southern Sweden is decreasing, primarily in children and women who traditionally have had the highest risk of CD. CD was diagnosed most frequently in children 3-9 years old. There were regional variations in incidence. CD was most common in small towns, pointing to the importance of environmental factors in CD etiology.

Andean Crops Germination: Changes in the Nutritional Profile, Physical and Sensory Characteristics. A Review.

Andean crops such as quinoa, amaranth, cañihua, beans, maize, and tarwi have gained interest in recent years for being gluten-free and their high nutritional values; they have high protein content with a well-balanced essential amino acids profile, minerals, vitamins, dietary fiber, and antioxidant compounds. During the germination bioprocess, the seed metabolism is reactivated resulting in the catabolism and degradation of macronutrients and some anti-nutritional compounds. Therefore, germination is frequently used to improve nutritional quality, protein digestibility, and availability of certain minerals and vitamins; furthermore, in specific cases, biosynthesis of new bioactive compounds could occur through the activation of secondary metabolic pathways. These changes could alter the technological and sensory properties, such as the hardness, consistency and viscosity of the formulations prepared with them. In addition, the flavor profile may undergo improvement or alteration, a critical factor to consider when integrating sprouted grains into food formulations. This review summarizes recent research on the nutritional, technological, functional, and sensory changes occur during the germination of Andean grains and analyze their potential applications in various food products.

Foetal gluten immunogenic peptides during pregnancy: a new determinant on the coeliac exposome.

BACKGROUND: The increasing incidence of coeliac disease is leading to a growing interest in active search for associated factors, even the intrauterine and early life. The exposome approach to disease encompasses a life course perspective from conception onwards has recently been highlighted. Knowledge of early exposure to gluten immunogenic peptides (GIP) in utero could challenge the chronology of early prenatal tolerance or inflammation, rather than after the infant's solid diet after birth. METHODS: We developed an accurate and specific immunoassay to detect GIP in amniotic fluid (AF) and studied their accumulates, excretion dynamics and foetal exposure resulting from AF swallowing. One hundred twenty-five pregnant women with different gluten diets and gestational ages were recruited. RESULTS: GIP were detectable in AF from at least the 16th gestational week in gluten-consuming women. Although no significant differences in GIP levels were observed during gestation, amniotic GIP late pregnancy was not altered by maternal fasting, suggesting closed-loop entailing foetal swallowing of GIP-containing AF and subsequent excretion via the foetal kidneys. CONCLUSIONS: The study shows evidence, for the first time, of the foetal exposure to gluten immunogenic peptides and establishes a positive correlation with maternal gluten intake. The results obtained point to a novel physiological concept as they describe a plausible closed-loop circuit entailing foetal swallowing of GIP contained in AF and its subsequent excretion through the foetal kidneys. The study adds important new information to understanding the coeliac exposome.

Eating disorders, body image dissatisfaction and their association with gluten-free diet adherence among patients with celiac disease.

BACKGROUND: Considering the higher prevalence of psychological problems in patients with Celiac disease (CD), the current study aims to assess the prevalence of eating disorders (EDs) and body image disturbance in patients with CD and examine the possible correlation between EDs, body image dissatisfaction and distortion, and gluten-free diet (GFD) adherence in these patients. METHODS: In this cross-sectional study, 217 patients with CD (18-55 years old) were recruited randomly from the CD registry database. EDs and body image issues were assessed using the 26-item Eating Attitude Test (EAT-26) and Stunkard Figure Rating Scale (FRS), respectively. Adherence to GFD was evaluated by the Celiac Dietary Adherence Test (CDAT) questionnaire. RESULTS: The prevalence of EDs was 43.5%. Furthermore, the prevalence of body dissatisfaction and distortion was 65.9% and 41.1%, respectively. The logistic regression demonstrated a significant negative association between adherence to the GFD and EDs (OR = 2.09, 95% CI: 1.11-3.91, P = 0.022). However, there was no significant association between following GFD and body image dissatisfaction (OR = 1.70, CI: 0.92-3.17, P = 0.090), and distortion (OR = 0.65, CI: 0.36-1.18, P = 0.163). CONCLUSION: Considering the high prevalence of EDs in patients with CD and owing to the inverse association between EDs and GFD adherence, nutritionists should consider the psychological barriers in adhering to a GFD when consulting patients with CD.

Genome-wide association study reveals marker-trait associations for major agronomic traits in proso millet (Panicum miliaceum L.).

MAIN CONCLUSION: The pilot-scale genome-wide association study in the US proso millet identified twenty marker-trait associations for five morpho-agronomic traits identifying genomic regions for future studies (e.g. molecular breeding and map-based cloning). Proso millet (Panicum miliaceum L.) is an ancient grain recognized for its excellent water-use efficiency and short growing season. It is an indispensable part of the winter wheat-based dryland cropping system in the High Plains of the USA. Its grains are endowed with high nutritional and health-promoting properties, making it increasingly popular in the global market for healthy grains. There is a dearth of genomic resources in proso millet for developing molecular tools to complement conventional breeding for developing high-yielding varieties. Genome-wide association study (GWAS) is a widely used method to dissect the genetics of complex traits. In this pilot study of the first-ever GWAS in the US proso millet, 71 globally diverse genotypes of 109 the US proso millet core collection were evaluated for five major morpho-agronomic traits at two locations in western Nebraska, and GWAS was conducted to identify single nucleotide polymorphisms (SNPs) associated with these traits. Analysis of variance showed that there was a significant difference among the genotypes, and all five traits were also found to be highly correlated with each other. Sequence reads from genotyping-by-sequencing (GBS) were used to identify 11,147 high-quality bi-allelic SNPs. Population structure analysis with those SNPs showed stratification within the core collection. The GWAS identified twenty marker-trait associations (MTAs) for the five traits. Twenty-nine putative candidate genes associated with the five traits were also identified. These genomic regions can be used to develop genetic markers for marker-assisted selection in proso millet breeding.

Celiac Disease and Autoimmune Diseases in a Pediatric Population in Morocco: A Cross-Sectional Study.

INTRODUCTION: Celiac disease (CD) is defined as an autoimmune disease (AD) caused by gluten ingestion in genetically sensitive individuals. Several publications have demonstrated the increased risk of AD in patients with CD, both adults and children, which requires systematic research. Our study aimed to determine the prevalence of AD in 60 patients diagnosed with CD and to highlight risk factors that may contribute to the emergence of AD. MATERIALS AND METHODS: We collected medical data from all CD patients under 16 years of age who also had AD. Our study was conducted in the Gastroenterology-Hepatology and Pediatric Nutrition Unit of the Pediatrics Department of the Mohamed VI Hospital and University Center in Oujda, Morocco, during a seven-year period between January 2017 and January 2024. RESULTS: We studied 60 patients with CD in our study. Eight patients (13%) had an associated AD. Their average age was eight years, with extremes varying between two and 15 years. AD was diagnosed before CD in six cases (75%), in parallel with CD in one patient (12.5%), while in only one case, it was diagnosed after CD (12.5%). All our patients had a single AD associated with CD. These ADs were mainly type 1 diabetes in seven cases and autoimmune thyroiditis in only one case. All our patients followed a gluten-free diet in addition to specific treatment for associated AD. Nevertheless, despite regular medical follow-up and targeted dietary advice for the management of CD and associated AD, three patients encountered difficulties in following the recommended diet. CONCLUSION: Younger patients with CD have an increased risk of hypothyroidism and insulin-dependent diabetes. These data necessitate improved surveillance to discover these illnesses as early as possible in order to optimize management and reduce related consequences.

Whole-genome sequencing and characterization of human fecal isolate Lacticaseibacillus casei LC130 from NORDBIOTIC collection.

We report the complete genome sequence of Lacticaseibacillus casei LC130, isolated from a healthy human fecal sample and part of the NORDBIOTIC collection. The 2.969 Mb genome of LC130 includes genes potentially involved in lactose metabolism and the production of bacteriocins, peptidases, and polyamines, suggesting potential health benefits.

Insight into the mechanism of the aggregation behavior of wheat protein modulated by l-lysine under microwave irradiation.

This study explored the mechanism of l-lysine intervention in wheat gluten protein (WG) gel formation under a microwave (MW) field. The results showed that the MW treatment had higher ζ-potential values at the same heating rate. After adding l-lysine, the solution conductivity and dielectric loss were significantly increased. Moreover, the WG gel strength enhanced 4.40% under the MW treatment. The Fourier spectra showed that the α-helix content was decreased 13.78% with the addition of lysine. The ultraviolet absorption spectra and fluorescence spectra indicated that MW irradiation impacted the interactions between WG molecules more effectively than the water bath heating, promoting the denaturation and unfolding of the protein structure. In addition, scanning electron microscopy analysis showed that the incorporation of lysine promoted an ordered network structure formation of the protein, which enhanced the gel properties. This indicated that the zwitterion of l-lysine played a regulatory role in the aggregation of proteins in the MW field.

Evolution in coeliac disease diagnosis and management.

The traditional gut-centric view of coeliac disease is evolving as immune and genetic insights underscore the central importance of a systemic, T cell immune response to gluten in disease pathogenesis. As the field increasingly recognize the limitations of small intestinal histology as the diagnostic standard, data supporting the accuracy of an immune (serologic) diagnosis of coeliac disease - well demonstrated in children - are growing for adults. Novel biomarkers such as interleukin-2 that identify the gluten-specific T cell demonstrate high sensitivity and specificity for coeliac disease and offer the potential for a diagnostic approach that avoids the need for gluten challenge. Asymptomatic disease and manifestations outside the gut pose considerable challenges for diagnosis using a case-finding strategy and enthusiasm for population screening is growing. The gluten-free diet remains a highly restrictive treatment and there is a paucity of controlled data to inform a safe gluten intake threshold. Ongoing symptoms and enteropathy are common and require systematic evaluation. Slowly-responsive disease is prevalent in the older patient diagnosed with coeliac disease, and super-sensitivity to gluten is an emerging concept that may explain many cases of nonresponsive disease. While there is great interest in developing novel therapies for coeliac disease, no drug has yet been registered. Efficacy studies are generally assessing drugs in patients with treated coeliac disease who undergo gluten challenge or in patients with nonresponsive disease; however, substantial questions remain around specific endpoints relevant for patients, clinicians and regulatory agencies and optimal trial design. Novel immune tools are providing informative readouts for clinical trials and are now shaping their design.

Evaluation of plant-derived biomaterials for the development of tissue-engineered corneal substitutes.

Corneal blindness affects over 10 million patients worldwide. Due to the limited supply of donor corneas and frequent graft failure, bioengineered alternatives are crucial. To overcome drawbacks associated with corneal substitutes from synthetic biomaterials, fabrication from plant-derived biomaterials is a potential alternative. Herein, soy protein and glutenin in combination with different crosslinkers were evaluated for fabrication of corneal substitutes. Optical, mechanical, and biochemical properties of fabricated constructs and control rabbit corneas were evaluated in vitro. Soy protein crosslinked with peroxidase/H202 possessed transparency and mechanical properties comparable to controls, although their water content and biocompatibility were inferior. In contrast, soy protein crosslinked with tannic acid showed similar water content, tensile strength, and biocompatibility as rabbit corneas; however, these constructs displayed significantly lower transparency and higher strain to failure. Finally, glutenin cross-linked using formaldehyde showed excellent transparency, strain to failure, and biocompatibility, however; they exhibited significantly lower water content and tensile strength than controls. This study is the first to establish CIELAB color values for the rabbit cornea, allowing quantitative optical evaluation of tissue-engineered substitutes. Thus, a crosslinking strategy utilizing plant-derived proteins for fabrication of constructs with properties comparable to rabbit corneas is a promising direction for development of tissue-engineered corneal substitutes.

The flavour of wheat gluten hydrolysate after Corynebacterium Glutamicum fermentation: Effect of degrees of hydrolysis and fermentation time.

Corynebacterium glutamicum was used to ferment wheat gluten hydrolysates (WGHs) to prepare flavour base. This study investigated the effect of hydrolysis degrees (DHs) and fermentation time on flavour of WGHs. During fermentation, the contents of amino nitrogen, total acid and small peptides increased, while the protein and pH value decreased. Succinic acid, GMP, and Glu were the prominent umami substances in fermented WGHs. The aromas of WGHs with different DHs could be distinguished by electronic nose and GC-IMS. Based on OAV of GC-MS, hexanal was the main compound in WGHs, while phenylethyl alcohol and acetoin were dominant after fermentation. WGHs with high DHs accumulated more flavour metabolites. Correlation analysis showed that small peptides (<1 kDa) could promote the formation of flavour substances, and Asp was potentially relevant flavour precursor. This study indicated that fermented WGHs with different DHs can potentially be used in different food applications based on flavour profiles.

Matrix-matched quantification of volatile organic compounds (VOCs) in gluten free flours and bakery products.

The aim of this study deals with characterize the volatile profiles of gluten free flours and bakery products. An appropriate HS-SPME/GC-MS methods for the quantification analyses was performed and corn starch solid as standards was used. 34 different samples were analysed, and 127 compounds distributed in 4 classes (alcohols, aldehydes and ketones, heterocyclic compounds, and terpenes), that make up the aroma of these gluten free, were identified. The developed method is characterized by detection limits of 0.0004 and 0.0047 mg/kg for camphor and pyrazine, respectively, and linearity of quantification standards were between 0.990 and 0.998 for a range of 3-50 mg/kg.

A Critical Appraisal of Gluten in Skin Disorders, the Evidence So Far, and Updated Recommendations.

Gluten, a polypeptide hapten, found in many cereals such as barley, wheat, rye, oats, and others, has been recently implicated in a range of cutaneous disorders ranging from chronic plaque psoriasis through psoriatic arthritis, urticaria (chronic as well as paediatric onset), and angioedema to lichen planus, vitiligo, and rosacea. The evidence for them is still not well reviewed. To generate evidence for the causal role of gluten in various dermatological disorders. The Pubmed, MedLine, and EMBASE databases were searched using the keywords "Gluten" and one of the dermatoses, namely, "Atopic Dermatitis", "Vasculitis", "Psoriasis", "Psoriatic Arthritis", "Acne", "Alopecia Areata", and "Immunobullous disorders". All articles published in English for which free full text was available were taken into consideration. The search strategy returned in a total of 1487 articles which were screened for relevance and elimination of duplicates. Ultimately, around 114 articles were deemed suitable. The data were extracted and presented in the narrative review format. A simple and cost-effective solution to many of these chronic and lifelong conditions is to restrict gluten in the diet. However, the dermatologist would do well to remember that in the vast majority of dermatological disorders including the ones listed here, gluten restriction is not warranted and can even lead to nutritional deficiencies. The evidence varied from Grade I for some disorders like psoriatic arthritis to Grade IV to most disorders like acne, vitiligo, vasculitis, and atopic dermatitis. Herein, we review the evidence for each of these conditions and make practical recommendations for gluten restriction in them.

Effects of steam explosion-modified rice bran dietary fiber on volatile flavor compounds retention and release of red date-flavored naan (ethnic specialty food of Xinjiang) during storage.

This study explored the effects of steam explosion-modified rice bran dietary fiber (S-RBDF) on red date-flavored naan quality and flavor characteristics. The results revealed that the rheological properties of the dough were improved with the incremental addition of S-RBDF (0-5%). The microstructure revealed that adding an appropriate amount of S-RBDF (1-5%) enabled more starch granules to be embedded in the dough network. Notably, the addition of 5% S-RBDF resulted in naan with an optimum specific volume and texture, which consumers preferred. Additionally, gas chromatography-mass spectrometry analysis showed that adding S-RBDF to naan contributed to the retention and sustained release of pleasant volatile compounds (e.g. red date flavor, etc.), while inhibiting the development of unpleasant volatile compounds by delaying the oxidation and decomposition of lipids and preserving the antioxidant phenolic compounds, thus contributing to flavor maintenance of naan during storage. Overall, these results provided a foundation for developing high-quality flavored naan.