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Coeliac disease is a common autoimmune disorder that affects nearly 1% of the general population. Current diagnostic strategies involve active case finding, serological tests, and endoscopy with biopsies. However, many patients with coeliac disease remain undiagnosed due to a wide gap between clinical guidelines and real-world practice in the diagnosis of adult coeliac disease. This highlights the need for increased education, training, and targeted quality-improvement interventions to optimise the diagnosis of coeliac disease. [ABSTRACT FROM AUTHOR]

Background: In mammals, amino acid metabolism has evolved to control immune responses. Tryptophan (Trp) is the rarest essential amino acid found in food and its metabolism has evolved to be a primary regulatory node in the control of immune responses. Celiac disease (CeD) is a developed immunological condition caused by gluten intolerance and is linked to chronic small intestine enteropathy in genetically predisposed individuals. Dendritic cells (DCs), serving as the bridge between innate and adaptive immunities, can influence immunological responses in CeD through phenotypic alterations. Objective: This review aims to highlight the connection between Trp metabolism and tolerogenic DCs, and the significance of this interaction in the pathogenesis of CeD. Results: It is been recognized that various DC subtypes contribute to the pathogenesis of CeD. Tolerogenic DCs, in particular, are instrumental in inducing immune tolerance, leading to T‐reg differentiation that helps maintain intestinal immune tolerance against inflammatory responses in CeD patients and those with other autoimmune disorders. T‐regs, a subset of T‐cells, play a crucial role in maintaining intestinal immunological homeostasis by regulating the activities of other immune cells. Notably, Trp metabolism, essential for T‐reg function, facilitates T‐reg differentiation through microbiota‐mediated degradation and the kynurenine pathway. Conclusion: Therefore, alterations in Trp metabolism could potentially influence the immune response in CeD, affecting both the development of the disease and the persistence of symptoms despite adherence to a gluten‐free diet. [ABSTRACT FROM AUTHOR]

Abstract Background In mammals, amino acid metabolism has evolved to control immune responses. Tryptophan (Trp) is the rarest essential amino acid found in food and its metabolism has evolved to be a primary regulatory node in the control of immune responses. Celiac disease (CeD) is a developed immunological condition caused by gluten intolerance and is linked to chronic small intestine enteropathy in genetically predisposed individuals. Dendritic cells (DCs), serving as the bridge between innate and adaptive immunities, can influence immunological responses in CeD through phenotypic alterations. Objective This review aims to highlight the connection between Trp metabolism and tolerogenic DCs, and the significance of this interaction in the pathogenesis of CeD. Results It is been recognized that various DC subtypes contribute to the pathogenesis of CeD. Tolerogenic DCs, in particular, are instrumental in inducing immune tolerance, leading to T‐reg differentiation that helps maintain intestinal immune tolerance against inflammatory responses in CeD patients and those with other autoimmune disorders. T‐regs, a subset of T‐cells, play a crucial role in maintaining intestinal immunological homeostasis by regulating the activities of other immune cells. Notably, Trp metabolism, essential for T‐reg function, facilitates T‐reg differentiation through microbiota‐mediated degradation and the kynurenine pathway. Conclusion Therefore, alterations in Trp metabolism could potentially influence the immune response in CeD, affecting both the development of the disease and the persistence of symptoms despite adherence to a gluten‐free diet.

Central to the diversity of wheat products was the origin of hexaploid bread wheat, which added the D-genome of Aegilops tauschii to tetraploid wheat giving rise to superior dough properties in leavened breads. The polyploidization, however, imposed a genetic bottleneck, with only limited diversity introduced in the wheat D-subgenome. To understand genetic variants for quality, we sequenced 273 accessions spanning the known diversity of Ae. tauschii. We discovered 45 haplotypes in Glu-D1, a major determinant of quality, relative to the two predominant haplotypes in wheat. The wheat allele 2 + 12 was found in Ae. tauschii Lineage 2, the donor of the wheat D-subgenome. Conversely, the superior quality wheat allele 5 + 10 allele originated in Lineage 3, a recently characterized lineage of Ae. tauschii, showing a unique origin of this important allele. These two wheat alleles were also quite similar relative to the total observed molecular diversity in Ae. tauschii at Glu-D1. Ae. tauschii is thus a reservoir for unique Glu-D1 alleles and provides the genomic resource to begin utilizing new alleles for end-use quality improvement in wheat breeding programs.

Background: Foods containing gluten and casein are widely consumed by children with autism spectrum disorder (ASD). Indeed, they are among their favorite foods. These foods contain carbohydrates, the primary substrate causing caries. Dental caries is one of the oral manifestations in children with ASD due to an imbalance in the demineralization and remineralization of tooth enamel. This study aimed to determine the relationship between food containing gluten and casein and the incidence of dental caries in children with ASD at the Biruku Indonesia Foundation (Bandung City, Java, Indonesia). Methods: This quantitative study used an analytical observational design with a cross-sectional approach. The research sample consisted of 17 subjects selected using the total sampling technique. Data were obtained after the Food Frequency Questionnaire (FFQ) and intraoral examination (DMFT/dmft score) were completed by the children’s parents. Correlation analysis was performed using Spearman’s rank test. Results: A total of 11 children, 64.7% had a low frequency of consuming food containing gluten and casein, whereas 6 children (35.3%) had a high frequency with a high dmft index (6.2) and a low DMFT index (1.5). Correlation analysis showed a negative correlation or inverse relationship between the two variables. Moreover, a significant relationship was found between consuming food containing gluten and casein and the dmft score (P value = 0.0498) and DMFT score (P value = 0.0383). Conclusion: Consuming food containing gluten and casein has a negative correlation or inverse relationship with dental caries in ASD children.

Background: Gluten-free foods often contain food additives to improve palatability, but the long-term effects on the human gastrointestinal tract are not well known. Aims: This study aimed to quantify frequency of food additive exposure in children with and without celiac disease (CD). Methods: Children with and without CD were enrolled and demographic data and three-day diet records were obtained. Foods were classified as gluten-free products (GFP) and "processed food", and were evaluated for presence of select food additives: polysorbate 80, carboxymethylcellulose, xanthan gum, guar gum, soy lecithin, titanium dioxide, carrageenan, maltodextrin, and aluminosilicates. The frequency of exposure was described. Results: Twenty-eight participants were included in final analysis. Children with CD had a higher number of daily exposures to xanthan gum (5.3 ± 3.1 vs 2.3 ± 2.4; p = 0.009), but similar exposures to the other additives. GFP contributed 29% of total calories in the GF diet. Both groups had similar intake of processed foods. Comparing GFP and gluten-containing processed foods, 68% vs. 25% contained at least one food additive of interest (p < 0.0001); in the celiac group, those with higher consumption of GFP tended to have a higher frequency of exposure to food additives (p = 0.09). Conclusion: A gluten-free diet and consumption of GFP may contribute to differences in food additive intake; quantifying food additive exposures and their effect on humans requires further study. [ABSTRACT FROM AUTHOR]

Background: Foods containing gluten and casein are widely consumed by children with autism spectrum disorder (ASD). Indeed, they are among their favorite foods. These foods contain carbohydrates, the primary substrate causing caries. Dental caries is one of the oral manifestations in children with ASD due to an imbalance in the demineralization and remineralization of tooth enamel. This study aimed to determine the relationship between food containing gluten and casein and the incidence of dental caries in children with ASD at the Biruku Indonesia Foundation (Bandung City, Java, Indonesia). Methods: This quantitative study used an analytical observational design with a cross-sectional approach. The research sample consisted of 17 subjects selected using the total sampling technique. Data were obtained after the Food Frequency Questionnaire (FFQ) and intraoral examination (DMFT/dmft score) were completed by the children's parents. Correlation analysis was performed using Spearman's rank test. Results: A total of 11 children, 64.7% had a low frequency of consuming food containing gluten and casein, whereas 6 children (35.3%) had a high frequency with a high dmft index (6.2) and a low DMFT index (1.5). Correlation analysis showed a negative correlation or inverse relationship between the two variables. Moreover, a significant relationship was found between consuming food containing gluten and casein and the dmft score (P value = 0.0498) and DMFT score (P value = 0.0383). Conclusion: Consuming food containing gluten and casein has a negative correlation or inverse relationship with dental caries in ASD children. [ABSTRACT FROM AUTHOR]

Purpose: A strategy to reduce starch digestibility is to limit its accessibility to α-amylase by preserving the integrity of cells where starch is encapsulated. Coarse flour is rich in intact cells and can be used for this purpose. However, making bread with coarse flour negatively affects crumb cohesiveness, which may increase the gastric disintegration rate, and enhance starch accessibility. Therefore, this study aimed to assess the combined effect of coarse semolina and its 20% gluten substitution in bread in healthy volunteers on glycemic and insulinemic responses, oral processing and bolus characteristics., Methods: Apparently, healthy volunteers (n = 16) randomly consumed bread made with coarse semolina and 20% gluten substitution (80CS&#95;20G), its counterpart with fine semolina (80FS&#95;20G), and bread with fine semolina and 5% gluten (95FS&#95;5G). The glycemic and insulinemic responses were measured over 2 h after bread consumption. Mastication behaviour, bolus properties and reducing sugar were also evaluated., Results: No differences in glycemic responses and mastication were observed among the samples. 80CS&#95;20G and 80FS&#95;20G exhibited similar textural properties but 80CS&#95;20G released less reducing sugars and elicited a lower insulin response at 30 min than 80FS&#95;20G, probably due to intact cells that limit starch accessibility. Also, 95FS&#95;5G released lower reducing sugars and had lower insulin peak than 80FS&#95;20G. The compact structure of 95FS&#95;5G may have delayed starch hydrolysis by restricting α-amylase accessibility., Conclusion: Combining gluten and coarse semolina resulted in bread with a lower release of reducing sugars, a reduced insulinemic peak and textural properties similar to the counterpart with fine semolina., Clinical Trial Registration Number: The trial is registered at ClinicalTrials.gov: NCT06152874., Competing Interests: Declarations Ethical approval The study was approved by the Institutional Review Board of the Department of Agricultural, Food, Environmental and Animal Sciences of the University of Udine (protocol number: 0003800 on July 18th 2023). Informed consent to participate All participants signed the informed consent according to the Helsinki Declaration on human rights. Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

This paper examines the role of dietary peptides gluten and casein in modulating brain function in individuals with autism spectrum disorder (ASD) from a biochemical perspective. Neurotransmitter systems and neural networks are crucial for brain function, and alterations at the biochemical level can contribute to the characteristic symptoms and behaviors of ASD. The paper explores how dietary peptides influence neurotransmitter systems and neural networks, highlighting their potential as interventions to improve brain function in ASD. The evidence suggests that dietary peptides can impact neurotransmitter synthesis, release, and receptor interactions, disrupting the balance of neurotransmitter systems and affecting neural network function. The findings underscore the potential of dietary interventions in modulating brain function in ASD and call for further research to elucidate the underlying mechanisms and optimize clinical practice. Considering individual dietary sensitivities and preferences, personalized dietary approaches may be necessary for optimal outcomes. Dietary interventions' timing, duration, and integration with other evidence-based treatments are crucial considerations. Safety considerations and regular monitoring are important to ensure the implementation of dietary interventions safely and effectively., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Objectives: The main treatment for celiac disease is a gluten-free diet. Gluten infection occurs in 55%-32% of these patients, which can cause symptoms in these patients. Many patients with celiac disease are dissatisfied with a gluten-free diet and are interested in a non-dietary alternative treatment. Methods: In this study, probiotic samples of local dairy (milk, yogurt, and cheese) from Iran were collected in sterile conditions and after enzymatic extraction using a lysis buffer and a sonication method for enzyme activity of prolyl endopeptidase and aminopeptidase N were evaluated. Results: The highest absorption rate for Z-Gly-Pro-4-nitroanilide substrate that performs the evaluation of prolyl endopeptidase enzyme, respectively, for strains C10-1 (L. pentosus), B6-1 (L. fermentum), C5-2 (L.paracasei), Y5 (L.paracasei) and C11-1 (L. pentosus) and in relation to Leu-p-NA which assesses aminopeptidase N The highest uptake was observed for strains K1 (L. helveticus), B8-2 (L. plantarum), Y5 (L.paracasei), P2-3 and P35 (L. plantarum), respectively. All of the above strains showed significantly different uptake than the negative control containing buffer and substrate (P

OBJECTIVE: This study aims to review the relevant bibliography about non-celiac gluten sensitivity in children and to summarize the main data of pathogenesis, symptomatology and diagnostic methods currently established, useful for clarifying the pediatric physician regarding this pathology. METHODS: The databases selected were: PubMed (The National Center for Biotechnology Information), LILACS (Latin American and Caribbean Health Sciences Literature) and SciELO (Scientific Electronic Library Online). Publications that contributed to the present review in the 2016-2021 interval, in English, Portuguese or Spanish, were chosen using the terms child, pediatrics, non-celiac gluten sensitivity and gluten sensitivity. RESULTS: Non-celiac gluten sensitivity occurs in patients in whom celiac disease and wheat allergy have been ruled out. Intestinal and extra-intestinal manifestations occur after eating gluten-containing foods and disappear after they are removed from the diet. The pathophysiological basis of non-celiac gluten sensitivity is related to the bodys innate immune response triggered by gluten peptides. The placebo-controlled double blind challenge test is considered the gold standard for diagnostic investigation, despite limitations. New methods are being tested in order to correctly affirm the diagnosis of non-celiac gluten sensitivity. CONCLUSION: The diagnostic determination of non-celiac gluten sensitivity is essential in order that the pediatric patient don’t be subjected, unnecessarily, to gluten-free diets that can have a negative impact on their nutrition and development.

Purpose: Children with celiac disease (CD) are at an increased risk of low bone mineral density (BMD) owing to malabsorption of fat-soluble vitamins, inflammation, and malnutrition. This study aimed to determine the prevalence and risk factors for low BMD in Iranian children with CD. Methods: This prospective cohort study examined 149 Iranian children with CD between 2011 and 2018 at Zabol University of Medical Sciences. BMD was measured using dual-energy X-ray absorptiometry. Demographic, clinical, and laboratory data were collected from patients' medical records. Logistic regression analysis was performed to identify the factors associated with low areal BMD (BMD-Z ←2) in the lumbar spine and femoral neck. Descriptive data were analyzed using the mean, standard deviation, and relative frequency. Data were analyzed using the chi-square test, t-test, and analysis of variance. Results: Of the 149 children with CD, 27.5% had osteoporosis. The mean body mass index (BMI) Z score was -1.28±1.2. Lower BMI was associated with a higher likelihood of BMD-Z (odds ratio 2.17; p≤0.05). Conclusion: Overall, the findings of this study showed that there was no correlation among Marsh classification, presence of specific human leukocyte antigens, and low BMD in Iranian children with CD. BMI can be a predictor of bone density in children with CD and may be applied clinically in early screenings to evaluate the bone health status in these children. [ABSTRACT FROM AUTHOR]

Eosinophilic esophagitis (EoE), a food antigen-mediated disease, is effectively treated with the dietary elimination of 6 foods commonly associated with food allergies (milk, wheat, egg, soy, tree nuts/peanuts, and fish/shellfish). Because wheat shares homologous proteins (including gluten) with barley and rye and can also be processed with these grains, some clinicians have suggested that barley and rye might also trigger EoE as a result of cross-reaction and/or cross-contamination with wheat. In this article, we discuss the theoretical risks of cross-reactivity and cross-contamination among wheat, barley, and rye proteins (including gluten); assess common practices at EoE treatment centers; and provide recommendations for dietary treatment and future studies of EoE.

Celiac disease (CD) is a systemic immune-mediated disorder caused by the dietary gluten in individuals who are genetically susceptible to the disease. In fact, CD is a T cell-mediated immune disease in which gluten-derived peptides activate the lamina propria CD4+ Teff cells, and these T-cell subsets can cause the intestinal tissue damages. Also, there are additional subsets of CD4+ T cells with suppressor functions. These subsets express the master transcription factor, FOXP3, and include Tr1 cells and CD4+CD25+ regulatory T cells (Tregs), which are the main population involved in maintaining the peripheral tolerance, preventing the autoimmune diseases and limiting the chronic inflammatory diseases such as CD. The suppressive function of Tregs is important to maintain the immune homeostasis. This paper examined the features and the basic mechanisms used by Tregs to mediate the suppression in CD.

Non-celiac gluten sensitivity (NCGS) is a term that is used to describe individuals who are not affected by celiac disease or wheat allergy, yet they have intestinal and/or extra-intestinal symptoms related to gluten ingestion with improvement of their symptoms upon withdrawing gluten from their diet. Gluten-related disorder groups are manifested by symptoms of gastrointestinal tract disorders, as well as hematological dermatological endocrinological, gynecological, rheumatological and nervous system symptoms. It is believed that NCGS represents heterogeneous groups with different subgroups characterized by different etiologies, clinical histories and clinical courses. There also appears to be an overlap between NCGS and irritable bowel syndrome (IBS). There is a need for establishing strict criteria for diagnosing NCGS. The absence of validated biomarkers remains a significant limitation for research studies on NCGS. New evidence shows that a gluten-free diet may be beneficial for some patients with gastrointestinal symptoms, such as those symptoms commonly found in patients with IBS. Further studies about NCGS are needed.

Objective: The human gut microbiota is composed of many viruses, bacteria, and fungi. Escherichia coli representatives are facultative anaerobic bacteria in the colon that play a crucial role in the metabolism of lactose, vitamin synthesis, and immune system modulation. E. coli forms a biofilm on the epithelial cell surface of the intestine that can be modified by diet compounds, i.e., gluten, xylitol, lactose, and probiotics., Methods: In the present study, the impact of probiotic-derived Lactobacillus rhamnosus GG strain on non-pathogenic E. coli biofilm was examined. The mono- and multispecies biofilm was also treated with gluten, xylitol, and lactose. We used 96-well plates to obtain biofilm growth. Biofilm was stained using crystal violet. To evaluate the type of interaction in mono- and multispecies biofilm, a new formula was introduced: biofilm interaction ratio index (BIRI). To describe the impact of nutrients on biofilm formation, the biofilm formation impact ratio (BFIR) was calculated., Results: The biofilms formed by both examined species are stronger than in monocultures. All the BIRI values were above 3.0. It was found that the monospecies biofilm of L. rhamnosus is strongly inhibited by gluten (84.5%) and the monospecies biofilm of E. coli by xylitol (85.5%). The mixed biofilm is inhibited by lactose (78.8%) and gluten (90.6%)., Conclusion: The relations between bacteria in the mixed biofilm led to changes in biofilm formation by E. coli and L. rhamnosus GG. Probiotics might be helpful in rebuilding the gut microbiota after broad spectrum antibiotic therapy, but only if gluten and lactose are excluded from diet., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The study of the changes in rheological properties and components during the processing of Chinese traditional handmade hollow dried noodle (HHDN) is essential to explaining the excellent quality of HHDN. The dynamic oscillation frequency sweep, stress relaxation, and uniaxial extension characteristics of the dough after kneading, stretching, and resting were investigated at six sampling points during the processing of HHDN. The result showed that stretching led to an increase in G' and G 0 , and a significant decrease (P < 0.05) in extensibility from 131.02 mm to 57.99 mm. Confocal laser scanning microscopy (CLSM) was used to observe the microstructure of the gluten network, which was destroyed during stretching and restored during resting. Studies of changes in components showed that the stretching process resulted in a decrease in GMP content from 3.24 (g/100 g) to 3.18 (g/100 g), and the resting process resulted in β-sheets decreasing significantly (P < 0.05). The degree of starch pasting increased significantly (P < 0.05) after stretching. The results of the correlation analysis showed that components changes were highly correlated with the rheological properties during the processing of HHDN., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Gastrointestinal disorders dysregulate the biochemical environment of the gastrointestinal tract by altering pH conditions during the gastric phase of digestion or by reducing the secretion of pancreatin during the intestinal part of the process. Ingested functional food could therefore lose some of its health-promoting potential apart from its nutritional value. In this work, we aimed to manufacture bread marked by decreased gluten content, using a commercial or laboratory sourdough, that could be appropriate for patients afflicted with wheat allergy, hypertension and pancreatic malfunctions. A reference sample (no sourdough) was prepared alongside wheat and wheat-rye bread samples-produced with either commercial or laboratory sourdough ( L. plantarum BS, L. brevis 1269, L. sanfranciscensis 20663). We measured the QQQPP allergen content (ELISA) in bread extracts digested in vitro and determined how these extracted components affect the level of active angiotensin and alpha amylase (spectrophotometry). We then elucidated how these properties changed when physiological digestion conditions (pH and pancreatin activity) were disturbed to mimic gastric hyperacidity, hypochlorhydria or exocrine pancreatic insufficiency. The key finding was that every tested type of bread produced with laboratory sourdough exhibited pronounced angiotensin-converting enzyme inhibition. The effect was preserved even in dysregulated digestive conditions. The use of laboratory sourdough prevented an increase in allergenicity when pancreatin was restricted as opposed to the commercial sourdough, which surpassed the reference sample reading at 50% pancreatin. No statistically consistent link was reported when the inhibition of alpha amylase was assayed. In conclusion, functional bread manufactured with sourdough composed of L. plantarum BS, L. brevis 1269, and L. sanfranciscensis 20663 was shown to be potentially capable of contributing to the treatment against hypertension as evidenced by in vitro research. It was also moderately safer with regard to its allergenicity.

The influence of four carbon and nitrogen substrates on the quality and flavor of a novel surimi-based product fermented with Actinomucor elegans (A. elegans) was investigated, with a focus on carbon and nitrogen catabolite repression. The results showed that the substrate significantly affected mycelial growth, enzyme activities, and the metabolites of A. elegans. Although glucose significantly promoted A. elegans growth by 116.69%, it decreased enzyme secretion by 69.79% for α-amylase and 59.80% for protease, most likely by triggering the carbon catabolite repression pathway. Starch, soy protein, and wheat gluten substantially affected the textural properties of the fermented surimi. Furthermore, wheat gluten significantly promoted the protease activity (102.70%) and increased protein degradation during surimi fermentation. The fishy odor of surimi was alleviated through fermentation, and a correlation between the volatile compounds and A. elegans metabolism was observed. These results explore fermentation substrates in filamentous fungi metabolism from a catabolite repression perspective., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

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., (© 2024. The Author(s).)

Background & Aims: Celiac disease (CD) is a chronic inflammatory disease of the small intestine induced and maintained by gluten ingestion in susceptible individuals. Current treatment consists of strict adherence to a lifelong gluten-free diet (GFD) which is considered safe and effective in the large majority of patients. However, since adherence to a GFD is difficult and has a negative impact on quality of life, an increasing interest in other treatment options has emerged. Moreover, in some individuals a GFD is not sufficiently effective, necessitating alternative treatments., Methods: By performing a systematic search, we constructed a detailed narrative review. Only treatment options considered relevant and conducted in a phase I, II or III clinical trial were included., Results: Based on the pathophysiology of CD, four major therapeutic approaches can be distinguished: firstly, by focusing on intraluminal gluten detoxification before absorption occurs, secondly, by modulating intestinal permeability and preventing paracellular uptake, thirdly, by enhancing immunological tolerance to gluten and finally, by regulating gluten auto-immunity., Conclusions: Despite significant efforts, no treatment has yet completed a phase III clinical trial. Future studies will likely focus on the use of supplemental drugs in conjunction to a GFD, with ALV003 and ZED-1227 currently being the most promising therapeutic options., Competing Interests: Conflict of interest None to declare., (Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Obesity is closely associated with non-alcoholic fatty liver disease (NAFLD), characterized by hepatic fat accumulation and hepatocyte injury. Preclinical studies have shown exacerbated weight gain associated with an obesogenic gluten-containing diet. However, whether gluten affects obesity-induced hepatic lipid accumulation still remains unclear. We hypothesized that gluten intake could affect fatty liver development in high-fat diet (HFD)-induced obese mice. Thus, we aimed to investigate the impact of gluten intake on NAFLD in HFD-induced obese mice. Male apolipoprotein E-deficient (Apoe-/-) mice were fed with a HFD containing (GD) or not (GFD) vital wheat gluten (4.5%) for 10 weeks. Blood and liver were collected for further analysis. We found that gluten exacerbated weight gain, hepatic fat deposition, and hyperglycemia without affecting the serum lipid profile. Livers of the GD group showed a larger area of fibrosis, associated with the expression of collagen and MMP9, and higher expression of apoptosis-related factors, p53, p21, and caspase-3. The expression of lipogenic factors, such as PPARγ and Acc1, was more elevated and factors related to beta-oxidation, such as PPARα and Cpt1, were lower in the GD group compared to the GFD. Further, gluten intake induced a more significant expression of Cd36, suggesting higher uptake of free fatty acids. Finally, we found lower protein expression of PGC1α followed by lower activation of AMPK. Our data show that gluten-containing high-fat diet exacerbated NAFLD by affecting lipogenesis and fatty acid oxidation in obese Apoe-/- mice through a mechanism involving lower activation of AMPK., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Intestinal permeability is a physiological property that allows necessary molecules to enter the organism. This property is regulated by tight junction proteins located between intestinal epithelial cells. However, various factors can increase intestinal permeability (IIP), including diet. Specific components in the Western diet (WD), such as monosaccharides, fat, gluten, salt, alcohol, and additives, can affect the tight junctions between enterocytes, leading to increased permeability. This review explains how these components promote IIP and outlines their potential implications for health. In addition, we describe how a reduction in WD consumption may help improve dietary treatment of diseases associated with IIP. Research has shown that some of these components can cause changes in the gut microbiota, leading to dysbiosis, which can promote greater intestinal permeability and displacement of endotoxins into the bloodstream. These endotoxins include lipopolysaccharides derived from gram-negative bacteria, and their presence has been associated with various diseases, such as autoimmune, neurological, and metabolic diseases like diabetes and cardiovascular disease. Therefore, nutrition professionals should promote the reduction of WD consumption and consider the inclusion of healthy diet components as part of the nutritional treatment for diseases associated with increased intestinal permeability.

Background. The prevalence of functional bowel disorders is on the rise worldwide. Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder characterized mainly by abdominal cramps, flatulence, and abnormal bowel movements. Due to the lack of specific biomarkers and of a specific diagnostic test, IBS is diagnosed according to the Rome IV clinical criteria. The current holistic approach recommends dietary management as the initial therapy for IBS patients with mild and moderate symptoms. Objectives. This review examines the studies on the effect of various types of diets on IBS as well as on the primary dietary therapy in IBS patients. Material and methods. A literature review of published studies was conducted by searching the Medline-PubMed database using the MeSH (Medical Subject Headings) descriptor and the following keyword combinations: “irritable bowel syndrome” and “treatment” (n = 11 articles), “irritable bowel syndrome” and “diet or nutrition” (n = 26 articles), “irritable bowel syndrome” (n = 9 articles), and “gluten”, “irritable bowel syndrome” and “lactose” (n = 4 articles). Results. Contradictory results were found in many studies regarding several diets such as diet excluding gas-producing foods, diet low in lactose, gluten-free diet, diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) and the role of fiber, alcohol, caffeine, and natural remedies and their applications in different IBS subtypes. Conclusions. Short-term restriction of FODMAP may be the most effective dietary intervention for reducing IBS symptoms compared to other types of diet. [ABSTRACT FROM AUTHOR]

Analysis of gene expression in developing wheat seeds was used to identify a gene, wheat bread making (wbm), with highly differential expression (~1000 fold) in the starchy endosperm of genotypes varying in bread making quality. Several alleles differing in the 5'-upstream region (promoter) of this gene were identified, with one present only in genotypes with high levels of wbm expression. RNA-Seq analysis revealed low or no wbm expression in most genotypes but high expression (0.2-0.4% of total gene expression) in genotypes that had good bread loaf volume. The wbm gene is predicted to encode a mature protein of 48 amino acids (including four cysteine residues) not previously identified in association with wheat quality, possibly because of its small size and low frequency in the wheat gene pool. Genotypes with high wbm expression all had good bread making quality but not always good physical dough qualities. The predicted protein was sulphur rich suggesting the possibility of a contribution to bread loaf volume by supporting the crossing linking of proteins in gluten. Improved understanding of the molecular basis of differences in bread making quality may allow more rapid development of high performing genotypes with acceptable end-use properties and facilitate increased wheat production.

Celiac disease (CeD) is a systemic, immune-mediated enteropathy, which is triggered by gluten protein in genetically susceptible individuals. CeD, once thought to be an uncommon disease, is now recognized to affect approximately 40-60 million people globally. While CeD is now well reported from a few Asian countries such as India, China, Pakistan, and Middle Eastern countries; it is still believed to be uncommon in the rest of Asia. Gluten-related diseases other than CeD, like non-celiac gluten sensitivity (NCGS) are also emerging globally. CeD and NCGS may present with either intestinal or extra-intestinal symptoms, and a proportion of them have overlapping symptoms with irritable bowel syndrome. Hence, many of them are misdiagnosed as having irritable bowel syndrome in clinical practice. In this review, we discuss the emergence of CeD and other gluten-related disorders, both globally and in Asia, the overlapping manifestations between gluten-related disorders and irritable bowel syndrome, and the challenges associated with diagnosis and management of CeD in Asia. [ABSTRACT FROM AUTHOR]

Wheat dependent exercised induced anaphylaxis (WDEIA) is common in Asian adult populations especially in northern China and Korea. A classical WDEIA case is presented with detailed histories, investigations and management plans. Serum specific IgE to omega-5 gliadin is critical for the diagnosis of WDEIA. Avoidance from wheat and exercise are the keys for prevention of anaphylaxis. Omalizumab, a monoclonal antibody against IgE, is reserved for cases with recurrent anaphylaxis and active physical activity status and it is an off-label treatment.

Background/Aim. Primary biliary cholangitis (PBC) is an immune-mediated chronic cholestatic disease of liver, with a slow progression. The aim of our study was to determine the correlation of PBC, atrophic gastritis (AG) and gluten-sensitive enteropathy (GSE), to identify the macroscopic and histopathological modifications of gastric and duodenal mucosa which occur in PBC and to analyze the frequency of these changes compared to a control group. Methods. This study included 50 patients with PBC and 46 control subjects with the dyspeptic symptoms, without liver disease. All of the examined subjects underwent esophagogastroduodenoscopy. Macroscopic and histopathological findings of the gastric and duodenal mucosal samples were recorded and analyzed. Results. There was no statistically significant association between the PBC and AG, or between the PBC and Helicobacter pylori infection. There was a highly significant difference in the frequency of Helicobacter pylori infection and the presence of GSE in the patients in the control group compared to those with PBC. Conclusions. The patients with PBC are at a lower risk for Helicobacter pylori infectionand atrophic gastritis. Testing for GSE in the PBC patients may be beneficial, considering the higher incidence of GSE amongst these patients. GSE represents a risk factor for the presence of PBC and the patients with GSE are nearly four times more likely to have PBC.

Background & aimsThe ingestion by rats of different proteins causes large differences in the plasma ratio of tryptophan to other large neutral amino acids, which predicts brain tryptophan uptake and serotonin synthesis. We evaluated in humans whether ingesting these proteins also produces large excursions in the tryptophan ratio.MethodsFasting males (n = 6) ingested V-8 Juice containing 40 g of α-lactalbumin, gluten, zein or starch. Blood was drawn before and at 30 min intervals after ingestion for 4 h; tryptophan and other large neutral amino acids were quantitated.ResultsPre-meal plasma tryptophan was ~50 nmol/ml; the tryptophan ratio was ~0.010. α-Lactalbumin increased plasma tryptophan (3-fold) and the tryptophan ratio (50%); starch did not change either tryptophan variable, while gluten caused a modest (25%) and zein a large reduction (50%) in plasma tryptophan. Gluten and zein reduced the tryptophan ratio. The maximal difference in the tryptophan ratio occurred between α-lactalbumin and zein and was large (~3-fold).ConclusionSince the plasma tryptophan ratio predicts brain tryptophan uptake and serotonin synthesis in rats, the differences in the ratio produced in humans by these proteins may modify serotonin synthesis, and perhaps elicit serotonin-linked changes in behavior.

Metal ions have been considered as an important factor on fibrils assembly. Herein, a comprehensive analysis of specific ions effect on fibril formation and structural changes was investigated. The addition of ions (except Zn 2+ ) accelerated the aggregation kinetics of rice glutelin fibrils (RGFs) from 0.93 to 1.28-2.19 h -1 . In addition, the fibrillization rate followed the order of NH 4 + > Li + > Na + > K + > Cu 2+ > Mg 2+ > Ca 2+ > Zn 2+ . The highest yield and length of fibrils were observed with Ca 2+ , probably due to the ionic bridging effect and hydrated capacity of Ca 2+ . However, Cu 2+ reduced the fibrils yield, which was attributable to the fact that Cu 2+ disrupted β-sheet structure and inhibited the transition of monomer to fibrils. The polymorphism of fibrils was observed with different salts, and the light metals presented a superior effect on fibrils formation than heavy metals. Overall, this work will provide a further information into how to tune the structure of RGFs using various ions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The current management of metabolic dysfunction-associated steatotic liver disease (MASLD) relies on lifestyle intervention. Prior studies have shown that nutritional wheat amylase trypsin inhibitors (ATI) activate toll-like receptor 4 on intestinal myeloid cells to enhance intestinal and extra-intestinal inflammation, including the promotion of murine MASLD, insulin resistance and liver fibrosis., Aims: We aimed to assess the impact of ATI (gluten)-free diet in liver as well as metabolic parameters of biopsy-proven MASLD patients., Methods: We performed a 6-week, proof-of-concept 1:1 randomised controlled trial of an ATI-free diet. The controls followed a balanced diet recommended by the German Nutrition Society. We assessed changes in controlled attenuation parameter (CAP), body mass index (BMI) and homeostatic model assessment of insulin resistance (HOMA-IR). Patient-reported outcomes were assessed by the CLDQ-NASH questionnaire. Forty-five patients were consecutively enrolled (21 in the intervention arm and 24 in the control arm)., Results: Three patients from each arm discontinued the study. In the ATI-free diet group, a significant decrease in BMI (p = 0.018), CAP (p = 0.018) and HOMA-IR (p = 0.042) was observed at 6 weeks. The mean difference in CAP between the two arms at week 6 was 30.5 dB/m (p = 0.039), with a delta significantly higher in the ATI-free diet group (p = 0.043). Only an ATI-free diet could achieve a significant improvement in CLDQ-NASH domains (p value for total scoring: 0.013)., Conclusions: A short-term ATI-free diet leads to significant improvements in liver and metabolic parameters, as well as patient-reported outcomes with good tolerability. A larger follow-up study is justified to corroborate these findings., Clinical Trial Number: NCT04066400., (© 2024 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

The development of three-dimensional (3D) printed meat analogs with fiber, texture, and sensory resembling meat remains challenging. This study investigated the effect of l-cysteine on functionality enhancement and fibrous structure formation in mixtures of mung bean protein isolate (MBPI) and wheat gluten (WG) for meat analog production. 3D printing was used to construct fibrous filaments. Raw MBPI-WG mixtures decreased rheological properties when increasing l-cysteine contents (0.0%-0.6%), promoting ink extrudability. The cys-0.4% ink exhibited the highest printing resolution and structural stability, correlated with its higher mechanical strength and increased disulfide cross-links. After cooking, the cys-0.4% sample showed a pronounced fibrousness in agreement with its microstructure image. This meat analog displayed a muscle-meat-like structure, improved texture, and reduced beany odor and bitter taste. Excessive cysteine contents (0.5%-0.6%) negatively affected the functionality of meat analogs. This study provides guidance for optimizing the amount of l-cysteine in meat analogs to improve product quality., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Celiac disease (CeD) is a chronic immune-mediated enteropathy, which occurs in genetically predisposed individuals by the ingestion of gluten proteins present in wheat, barley and rye. The global pooled prevalence of CeD is 0.7% and it has been reported from nations all around the globe and can affect individuals of any age. It has a wide clinical spectrum ranging from being asymptomatic to being symptomatic with severe manifestations. Though initial descriptions of CeD focused on the classical presentation with gastrointestinal manifestations, in recent years it has been found that more patients have non-classical manifestations such as anemia, osteoporosis, increased transaminases, failure to thrive or short stature. The definitive diagnosis of CeD is based on a combination of clinical history, serologic testing with/without examination of duodenal biopsies. The preferred initial serologic test regardless of age for the detection of CeD is the tissue transglutaminase (IgA anti-tTG). Children with a high tTG-IgA (≥10 ULN) AND a positive anti-endomysial IgA antibody (EMA) can be diagnosed to have CeD without the need for duodenal biopsies. The rest should undergo biopsies with at least 4 biopsies from the distal duodenum and at least 1 from the bulb. A correctly orientated biopsy showing increased intraepithelial cells and a villous to crypt ratio of <2 is suggestive of CeD. The management of CeD is a lifelong complete dietary avoidance of gluten. IgA-TGA acts as a surrogate marker for healing of the small-bowel mucosa and should be performed every 6 mo until normalization and then every 12-24 mo thereafter., (© 2023. Crown.)

Western diets are rich in gluten-containing products, which are frequently poorly digested. The human large intestine harbors microorganisms able to metabolize undigested gluten fragments that have escaped digestion by human enzymatic activities. The aim of this work was obtaining and culturing complex human gut microbial communities derived from gluten metabolism to model the dynamics of healthy human large intestine microbiota associated with different gluten forms. For this purpose, stool samples from six healthy volunteers were inoculated in media containing predigested gluten or predigested gluten plus non-digested gluten. Passages were carried out every 24 h for 15 days in the same medium and community composition along time was studied via V3-V4 16S rDNA sequencing. Diverse microbial communities were successfully obtained. Moreover, communities were shown to be maintained in culture with stable composition for 14 days. Under non-digested gluten presence, communities were enriched in members of Bacillota , such as Lachnospiraceae , Clostridiaceae , Streptococcaceae , Peptoniphilaceae , Selenomonadaceae or Erysipelotrichaceae , and members of Actinomycetota , such as Bifidobacteriaceae and Eggerthellaceae . Contrarily, communities exposed to digested gluten were enriched in Pseudomonadota . Hence, this study shows a method for culture and stable maintenance of gut communities derived from gluten metabolism. This method enables the analysis of microbial metabolism of gluten in the gut from a community perspective.

To better understand the hypoglycemic potential of wheat gluten (WG), we screened dipeptidyl peptidase IV (DPP-4) inhibitory active peptides from WG hydrolysates. WG hydrolysates prepared by ginger protease were found to have the highest DPP-4 inhibitory activity among the five enzymatic hydrolysates, from which a 1-3 kDa fraction was isolated by ultrafiltration. Further characterization of the fraction with nano-HPLC-MS/MS revealed 1133 peptides. Among them, peptides with P' 2 (the second position of the N-terminal) and P 2 (the second position of the C-terminal) as proline residues (Pro) accounted for 12.44% and 43.69%, respectively. The peptides including Pro-Pro-Phe-Ser (PPFS), Ala-Pro-Phe-Gly-Leu (APFGL), and Pro-Pro-Phe-Trp (PPFW) exhibited the most potent DPP-4 inhibitory activity with IC 50 values of 56.63, 79.45, and 199.82 μM, respectively. The high inhibitory activity of PPFS, APFGL, and PPFW could be mainly attributed to their interaction with the S2 pocket (Glu205 and Glu206) and the catalytic triad (Ser630 and His740) of DPP-4, which adopted competitive, mixed, and mixed inhibitory modes, respectively. After comparative analysis of PPFS, PPFW, and PPF, Ser was found to be more conducive to enhancing the DPP-4 inhibitory activity. Interestingly, peptides with P 2 as Pro also exhibited good DPP-4 inhibitory activity. Meanwhile, DPP-4 inhibitory peptides from WG showed excellent stability, suggesting a potential application in type 2 diabetes (T2DM) therapy or in the food industry as functional components.

Background and Objective: Coeliac disease is a chronic, immune-mediated disorder for which the only treatment consists of lifelong strict adherence to gluten-free diet (GFD). However, there is a lack of evidence-based guidelines on the GFD dietary management of coeliac disease. This position paper, led by the Special Interest Group in coeliac disease of the European Society of Pediatric, Gastroenterology Hepatology, and Nutrition, supported by the Nutrition Committee and the Allied Health Professionals Committee, aims to present evidence-based recommendations on the GFD as well as how to support dietary adherence., Methods: A wide literature search was performed using the MeSH Terms: "diet, gluten free," "gluten-free diet," "diets, gluten-free," "gluten free diet," and "coeliac disease" in Pubmed until November 8th, 2022., Results: The manuscript provides an overview of the definition of the GFD, regulations as basis to define the term "gluten-free," which foods are naturally gluten-free and gluten-containing. Moreover, it provides recommendations and educational tips and infographics on suitable food substitutes, the importance of reading food labels, risk of gluten cross-contact at home and in public settings, nutritional considerations as well as factors associated to dietary adherence based on available evidence, or otherwise clinical expertise., Conclusions: This position paper provides guidance and recommendations to support children with coeliac disease to safely adhere to a GFD., (© 2024 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Protein-based hydrogels with promising biocompatibility and biodegradability have attracted considerable interest in areas of epidermal sensing, whereas, which are still difficult to synchronously possess high mechanical strength, self-adhesion, and recoverability. Hence, the bio-polymer lignosulfonate-reinforced gluten organohydrogels (GOHL x ) are fabricated through green and simple food-making processes and the following solvent exchange with glycerol/water binary solution. Ascribing to the uniform distribution of lignosulfonate in gluten networks, as well as the noncovalent interactions (e.g., H-bond) between them, the resultant GOHL x exhibit favorable conductivity (∼14.3 × 10 -4  S m -1 ), toughness (∼711.0 kJ m -3 ), self-adhesion (a maximal lap-shear strength of ∼33.5 kPa), high sensitivity (GF up to ∼3.04), and durability (∼3000 cycles) toward shape deformation, which are suitable for the detection of both drastic (e.g., elbow and wrist bending) and subtle (e.g., swallowing and speaking) human movements even under -20 °C. Furthermore, the GOHL x is also biocompatible, degradable, and recoverable (by a simple kneading process). Thus, this work may pave a simple, green, and cheap way to prepare all-biomass-based, tough, sticky, and recoverable protein-based organohydrogels for epidermal strain sensing even in harsh environments., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Celiac disease is a common inflammatory disease of the small bowel that induces mucosal intestinal lesions. The disease is mediated by an immune response and triggered by the ingestion of gluten in genetically predisposed individuals. Gluten contains gliadin, a component found mostly in wheat, barley, and rye. This process leads to gastrointestinal malabsorption with symptoms such as diarrhea, constipation, abdominal pain, and distention. It has a prevalence of 1%-2% in the general adult population, who present with symptoms at any age, but is more frequently found in adult women in the 3rd or 4th decade of life. Recognition of the disease has increased, but it remains a challenge to diagnose. CT and MR enterography are noninvasive studies used for evaluation of small bowel neoplasms and inflammatory small bowel pathologic conditions such as celiac disease. The authors review the spectrum of intestinal and extraintestinal findings of celiac disease at CT and MR enterography, as well as its complications, and the importance of recognizing certain imaging features that help in the diagnosis of celiac disease. More common and specific findings of celiac disease such as inversion of the jejunoileal fold pattern and mesenteric lymphadenopathy are reviewed. More uncommon entities that are more frequently associated with refractory or untreated celiac disease, such as ulcerative jejunoileitis, cavitary mesenteric lymph node syndrome, and malignancies including small bowel adenocarcinoma and lymphoma, are described. © RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material. The slide presentation from the RSNA Annual Meeting is available for this article.