Fighting Celiac Disease: Improvement of pH Stability of Cathepsin L In Vitro by Computational Design.

Roughly 1% of the global population is susceptible to celiac disease (CD)-inheritable autoimmune inflammation of the small intestine caused by intolerance to gliadin proteins present in wheat, rye, and barley grains, and called gluten in wheat. Classical treatment is a life-long gluten-free diet, which is constraining and costly. An alternative approach is based upon the development and oral reception of effective peptidases that degrade in the stomach immunogenic proline- and glutamine-rich gliadin peptides, which are the cause of the severe reaction in the intestine. In previous research, we have established that the major digestive peptidase of an insect Tribolium castaneum-cathepsin L-hydrolyzes immunogenic prolamins after Gln residues but is unstable in the extremely acidic environment (pH 2-4) of the human stomach and cannot be used as a digestive aid. In this work, using molecular dynamics simulations, we discover the probable cause of the pH instability of cathepsin L-loss of the catalytically competent rotameric state of one of the active site residues, His 275. To "fix" the correct orientation of this residue, we designed a V277A mutant variant, which extends the range of stability of the peptidase in the acidic environment while retaining most of its activity. We suggest this protein as a lead glutenase for the development of oral medical preparation that fights CD and gluten intolerance in susceptible people.

Gluten-free diet attenuates the impact of exogenous vitamin D on thyroid autoimmunity in young women with autoimmune thyroiditis: a pilot study.

Although both exogenous vitamin D and a gluten-free diet were found to reduce thyroid antibody titers, no study investigated interactions between gluten intake and vitamin D status in patients with autoimmune thyroid disorders. The aim of the present study was to assess whether the gluten-free diet determines the effect of vitamin D treatment on thyroid autoimmunity and thyroid function in young women with autoimmune (Hashimoto's) thyroiditis. The study compared two groups of euthyroid premenopausal women with this disorder, matched for thyroid antibody titers: 31 women with non-celiac gluten sensitivity complying for at least 12 months with the gluten-free diet and 31 unaffected sisters of women with non-celiac gluten sensitivity remaining without any dietary intervention. Plasma titers of thyroid peroxidase and thyroglobulin antibodies, as well as plasma concentrations of thyrotropin, free thyroid hormones, prolactin, 25-hydroxyvitamin D and high-sensitive C-reactive protein were measured at entry and after a six-month follow-up. Moreover, at both time points, the structure parameters of thyroid homeostasis were assessed. Although exogenous vitamin D decreased titers of thyroid peroxidase and thyroglobulin antibodies and increased 25-hydroxyvitamin D levels in each treatment group, this effect was less pronounced in patients on the gluten-free diet than in patients not following any dietary recommendations. Only in the latter group of patients, vitamin D increased SPINA-GT. Treatment-induced changes in thyroid peroxidase and thyroglobulin antibodies correlated with the impact of treatment on 25-hydroxyvitamin D levels. The obtained results suggest that gluten-free diet may impair beneficial effects of exogenous vitamin D in individuals with Hashimoto's thyroiditis.

[Development of a daily diet for children with celiac disease in municipal pre-school educational institutions].

Improving the quality of nutrition for children with gluten intolerance in preschool institutions is an important state task. Relevant adjustment of the diet enables to reduce the risk of the celiac syndrome. Balanced nutrient composition of diet is necessary for the harmonious growth and development of a child. The aim of the research was to develop specialized diet for children with gluten intolerance and celiac desease in municipal preschool educational institutions. Material and methods. A study of the 10-days full-day menu of children aged 3 to 7 years was carried out. To compose the specialized menu, we used the computational program "MDOU Calculate menu. Universal program for kindergarten". Technological maps of dishes in municipal preschool educational institutions were used. The calculation of the supply of the diet with vitamins, minerals and trace elements and the deviation of the nutritional and energy value of the diet from the recommended daily intake was made. Results. The necessity of developing a specialized diet for children 3-7 years old with a confirmed diagnosis of celiac disease, as well as for children on a gluten-free diet has been substantiated. A specialized daily food ration has been developed, consisting of four meals. Analysis of the nutritional and energy value of the dishes offered in the menu showed the minimum deviation of the obtained indicators from recommended daily intake. The necessity of introducing the developed diet into the system of specialized nutrition in preschool educational institutions has been substantiated. Conclusion. The results of the work indicate that under the conditions of state funding, there is a possibility of adjusting the existing food rations for the full-fledged socialization of children with various diseases.

[Selenium content in gluten-free products].

Special diets are used for the treatment and prevention of diseases of the digestive system, taking into account individual food intolerance and possible allergic reactions. The monotony of the diet due to the limited range of recommended foods and dishes negatively affects both the effectiveness of the treatment of gluten intolerance, and the provision of the body with essential and replaceable nutrients. The aim of this study was to determine the selenium content in the flour of gluten-free crops (rice, corn, buckwheat and amaranth), their mixtures, as well as in dishes (pancakes) from a mixture of amaranth and buckwheat flours. Material and methods. The following raw materials were used in the study: amaranth flour, unboiled buckwheat groats, whole grain rice flour and corn flour. By mixing the components in a laboratory mixer, dry gluten-free compositions were obtained: a mixture of amaranth flour and flour from native buckwheat; a mixture of amaranth and rice flour and a mixture of amaranth and corn flour in the ratio of 1:2 and 1:1; and a mixture of amaranth, buckwheat and corn flour in equal proportions. In laboratory baking of pancakes, mixtures of amaranth flour and flour from native buckwheat were used. The selenium content was determined by atomic absorption spectroscopy with electrothermal atomization after wet mineralization of the samples. Results. The results of the study showed that amaranth, buckwheat and corn are rich sources of selenium. The most valuable source of selenium was amaranth flour (515 µg/kg). Selenium content in native buckwheat flour and corn flour was 405 and 458 µg/kg, respectively. The lowest selenium content among the studied crops was found in rice flour (135 µg/kg). Selenium content in flour mixtures of the studied cultures ranged from 258 to 522 µg/kg. The highest values of selenium content were observed in mixtures of amaranth with corn flour (516-522 µg/kg). The lowest content of this trace element was found in mixtures containing rice flour (from 258 to 325 µg/kg). Selenium content in pancakes made from mixtures of amaranth flour and native buckwheat flour varied from 290 to 326 µg/kg. The calculation showed that the consumption of a portion of pancakes (50 g) by school-age children will satisfy their daily requirement for selenium by 7.3-8.1%. Conclusion. Regular inclusion of amaranth-based foods in the diet of children with gluten intolerance can positively affect the elimination of selenium deficiency.

Discriminative T-cell receptor recognition of highly homologous HLA-DQ2-bound gluten epitopes.

Celiac disease (CeD) provides an opportunity to study the specificity underlying human T-cell responses to an array of similar epitopes presented by the same human leukocyte antigen II (HLA-II) molecule. Here, we investigated T-cell responses to the two immunodominant and highly homologous HLA-DQ2.5-restricted gluten epitopes, DQ2.5-glia-α1a (PFPQPELPY) and DQ2.5-glia-ω1 (PFPQPEQPF). Using HLA-DQ2.5-DQ2.5-glia-α1a and HLA-DQ2.5-DQ2.5-glia-ω1 tetramers and single-cell αß T-cell receptor (TCR) sequencing, we observed that despite similarity in biased variable-gene usage in the TCR repertoire responding to these nearly identical peptide-HLA-II complexes, most of the T cells are specific for either of the two epitopes. To understand the molecular basis of this exquisite fine specificity, we undertook Ala substitution assays revealing that the p7 residue (Leu/Gln) is critical for specific epitope recognition by both DQ2.5-glia-α1a- and DQ2.5-glia-ω1-reactive T-cell clones. We determined high-resolution binary crystal structures of HLA-DQ2.5 bound to DQ2.5-glia-α1a (2.0 Å) and DQ2.5-glia-ω1 (2.6 Å). These structures disclosed that differences around the p7 residue subtly alter the neighboring substructure and electrostatic properties of the HLA-DQ2.5-peptide complex, providing the fine specificity underlying the responses against these two highly homologous gluten epitopes. This study underscores the ability of TCRs to recognize subtle differences in the peptide-HLA-II landscape in a human disease setting.

[Gluten-free diet in the treatment of extra-intestinal forms of gluten intolerance].

Following a gluten-free diet is recommended by clinical guidelines in the presence of gluten intolerance. However, due to the variety of clinical picture of various forms of intolerance, the elimination of gluten occurs not always timely. There are also diseases that classic treatment regimen does not include diet therapy, however, studies have confirmed the effectiveness of its use. The aim of the research - to study current data on the effectiveness of a gluten-free diet for extra-intestinal manifestations of gluten intolerance. Material and methods. Literature data concerning the effectiveness of including a gluten-free diet in the treatment of various diseases according to the PubMed and eLIBRARY portal were studied. Results. Modern data on the forms of gluten intolerance and their clinical manifestations are presented. The results of both randomized studies and individual clinical cases of gluten intolerance that occurred under the guise of other diseases are presented. A clinical case of an acute onset of the disease - celiac crisis, accompanied by acute diarrheal syndrome with subsequent malabsorption and progressive loss of body weight, anasarca and electrolyte disorders is considered. Neurological and psycho-neurological manifestations of celiac disease are described, including current data on the results of including a glutenfree diet in the treatment of autism spectrum disorders. The question of using dietary therapy for autism remains controversial to nowadays. The article outlines the arguments of supporters and opponents of excluding gluten in this pathology. Particular attention is paid to the diagnosis of gluten intolerance in patients with hematological disorders. The significance of a complete survey to identify celiac disease and timely diet therapy of the disease under stunted growth in children, after excluding other causes of malabsorption and even in the presence of negative serological markers of celiac disease is shown. The article also contains information on the pathology of kidneys and reproductive system, which were leveled only after the exclusion of gluten from the diet. Conclusion. The presented cases demonstrate a wide variety of clinical forms of gluten intolerance, examples of diagnostic search and dynamics of the clinical picture with the timely appointment of a gluten-free diet are given.

[Frequency of determining markers of casein's inhability and gluten in children with disorders of autistic spectrum].

The most optimal approach to the problem of managing children with autism spectrum disorders (ASD) is a complex one that involves a pediatric gastroenterologist, a nutritionist, a neurologist, a psychiatrist. Currently, there are studies that confirm the effectiveness of diet in the correction of neuropsychiatric status and gastroenterological disorders in ASD. Evidence supporting the therapeutic value of diets is limited and inconclusive. Diet therapy should be used only if food allergy or gluten or casein intolerance is diagnosed. Aim. To study the frequency of detection of markers of gluten and casein intolerance in children with ASD. Material and methods. The study involved 51 children (39 boys and 12 girls) aged 3 to 15 years with a diagnosis of ASD. Among the study participants, 20 children used gluten-free diet and casein-free diet for more than 6 months. The material for the study was venous blood taken from the elbow vein in the morning on an empty stomach. Determination of specific IgG-antibodies to casein and gliadin, IgA-antibodies to deamidized gliadin peptides was carried out by enzyme immunoassay. The level of total IgA to exclude selective deficiency was also determined. Results and discussion. Most children with ASD (79.5%) had increased levels of specific IgG antibodies to casein. The increase in IgG antigliadin antibodies was determined in 19.3% of children who do not follow a gluten-free diet, and antibodies to deamidized gliadin Ig peptides were not detected in any patient. Gluten intolerance in children with ASD is characterized by sensitivity to it and occurs in 40-50%. Conclusion. According to the literature and the results of own studies, some children with ASD have gluten and casein intolerance. Before the appointment of diet therapy for children with ASD, it is necessary to conduct a survey to clarify the nature of intolerance and the choice of optimal tactics of diet therapy.

Reproductive life in women with celiac disease; a nationwide, population-based matched cohort study.

STUDY QUESTION: How does celiac disease (CD) influence women's reproductive life, both prior to and after the diagnosis? SUMMARY ANSWER: Prior to the diagnosis of CD, an increased risk of adverse pregnancy outcomes was seen, whereas after the diagnosis, no influence on reproductive outcomes was found. WHAT IS KNOWN ALREADY: CD has been associated with several conditions influencing female reproduction and pregnancy outcomes including spontaneous abortion and stillbirth. STUDY DESIGN, SIZE, DURATION: A nationwide matched cohort study following 6319 women diagnosed with CD and 63166 comparison women and identifying reproductive events between the ages of 15 and 50 years. PARTICIPANTS/MATERIALS, SETTING, METHODS: Through linkage of several Danish national health registers, we identified all women diagnosed with CD between 1977 and 2016. We identified an age- and sex-matched comparison cohort and obtained data on reproductive outcomes for both cohorts. Adjusted stratified Cox and logistic regression models were used to estimate differences in reproductive outcomes between women with and without CD. MAIN RESULTS AND THE ROLE OF CHANCE: Comparing women with diagnosed CD with the non-CD women, the chance of pregnancy, live birth and risk of stillbirth, molar and ectopic pregnancy, spontaneous abortion and abortion due to foetal disease was the same. However, prior to being diagnosed, CD women had an excess risk of spontaneous abortion equal to 11 extra spontaneous abortions per 1000 pregnancies (adjusted odds ratio (OR) = 1.12, 95% CI: 1.03, 1.22) and 1.62 extra stillbirths per 1000 pregnancies (adjusted OR = 1.57, 95% CI: 1.05, 2.33) compared with the non-CD women. In the period 0-2 years prior to diagnosis fewer pregnancies occurred in the undiagnosed CD group, equal to 25 (95% CI: 20-31) fewer pregnancies per 1000 pregnancies compared to the non-CD group and in addition, fewer undiagnosed CD women initiated ART-treatment in this period, corresponding to 4.8 (95% CI: 0.9, 8.7) fewer per 1000 women compared to non-CD women. LIMITATIONS, REASONS FOR CAUTION: Validity of the diagnoses in the registers was not confirmed, but reporting to the registers is mandatory for all hospitals in Denmark. Not all spontaneous abortions will come to attention and be registered, whereas live- and stillbirths, ectopic and molar pregnancies and abortion due to foetal disease are unlikely not to be registered. We adjusted for several confounding factors but residual confounding cannot be ruled out. WIDER IMPLICATIONS OF THE FINDINGS: These findings suggest that undiagnosed CD can affect female reproduction and the focus should be on early detection of CD in risk groups. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the Health Research Fund of Central Denmark Region and The Hede Nielsens Foundation, Denmark. The authors report no conflicts of interest in this work.

[Efficient products from amaranth in a gluten-free nutrition of children with gluten intolerance].

The aim of the investigation was to evaluate the tolerability and effectiveness of the inclusion of products from amaranth to the regular children's diet during long glutenfree diet (GFD) therapy. The study included 37 children aged from 1 year to 17 years, the experience of compliance with a GFD was from 6 months to 16 years. Patients underwent an assessment of nutritional status: indicators of physical development by WHO percentile tables; clinical (erythrocytes, hemoglobin, leukocytes, lymphocytes, granulocytes) and biochemical (protein, albumin, iron, ionized calcium, selenium, copper) blood indicators. After that, children diet was supplemented with products from amaranth, which they constantly ate for 9-12 months. Quality and compliance difficulties of GFD were also examined using specially designed questionnaire filled in by parents. After 9-12 months of optimized GFD the examination of children and parents questioning was repeated. Long-term regular usage of amaranth products in GDB was accompanied by an improvement of indicators of nutritional status of patients: decrease in the number of children with underweight from from 16.25 to 10.8% and increase in the patients with normal body weight from 51.4 to 56.8%; reduction in the number of children with abnormal low rise from 10.8 to 5.4%, an increase of children with an average growth from 59.5 to 67.6%. The relative number of children with a decreased level of ionized calcium in the blood serum decreased from 37.8 to 10.8%. Normalization of decreased blood serum levels of iron, copper and zinc was observed in all patients who had a deficiency of these trace elements, in 13.5, 8 and 16.2% of children respectively. Difficulties in complying with the strict diet therapy are mainly social in nature. Products of amaranth tested in the course of the study were well tolerated, allergic and dyspeptic reactions were not noted. 89.2% of parents commented positively on the new gluten-free amaranth products.

Creation of the first ultra-low gluten barley (Hordeum vulgare L.) for coeliac and gluten-intolerant populations.

Coeliac disease is a well-defined condition that is estimated to affect approximately 1% of the population worldwide. Noncoeliac gluten sensitivity is a condition that is less well defined, but is estimated to affect up to 10% of the population, and is often self-diagnosed. At present, the only remedy for both conditions is a lifelong gluten-free diet. A gluten-free diet is often expensive, high in fat and low in fibre, which in themselves can lead to adverse health outcomes. Thus, there is an opportunity to use novel plant breeding strategies to develop alternative gluten-free grains. In this work, we describe the breeding and characterization of a novel ultra-low gluten (ULG) barley variety in which the hordein (gluten) content was reduced to below 5 ppm. This was achieved using traditional breeding strategies to combine three recessive alleles, which act independently of each other to lower the hordein content in the parental varieties. The grain of the initial variety was shrunken compared to wild-type barleys. We implemented a breeding strategy to improve the grain size to near wild-type levels and demonstrated that the grains can be malted and brewed successfully. The ULG barley has the potential to provide novel healthy foods and beverages for those who require a gluten-free diet.

Targeting of prolamins by RNAi in bread wheat: effectiveness of seven silencing-fragment combinations for obtaining lines devoid of coeliac disease epitopes from highly immunogenic gliadins.

Gluten proteins are responsible for the viscoelastic properties of wheat flour but also for triggering pathologies in susceptible individuals, of which coeliac disease (CD) and noncoeliac gluten sensitivity may affect up to 8% of the population. The only effective treatment for affected persons is a strict gluten-free diet. Here, we report the effectiveness of seven plasmid combinations, encompassing RNAi fragments from α-, γ-, ω-gliadins, and LMW glutenin subunits, for silencing the expression of different prolamin fractions. Silencing patterns of transgenic lines were analysed by gel electrophoresis, RP-HPLC and mass spectrometry (LC-MS/MS), whereas gluten immunogenicity was assayed by an anti-gliadin 33-mer monoclonal antibody (moAb). Plasmid combinations 1 and 2 downregulated only γ- and α-gliadins, respectively. Four plasmid combinations were highly effective in the silencing of ω-gliadins and γ-gliadins, and three of these also silenced α-gliadins. HMW glutenins were upregulated in all but one plasmid combination, while LMW glutenins were downregulated in three plasmid combinations. Total protein and starch contents were unaffected regardless of the plasmid combination used. Six plasmid combinations provided strong reduction in the gluten content as measured by moAb and for two combinations, this reduction was higher than 90% in comparison with the wild type. CD epitope analysis in peptides identified in LC-MS/MS showed that lines from three plasmid combinations were totally devoid of CD epitopes from the highly immunogenic α- and ω-gliadins. Our findings raise the prospect of breeding wheat species with low levels of harmful gluten, and of achieving the important goal of developing nontoxic wheat cultivars.

Plasma Alkylresorcinols Reflect Gluten Intake and Distinguish between Gluten-Rich and Gluten-Poor Diets in a Population at Risk of Metabolic Syndrome.

BACKGROUND: Many patients with celiac disease experience difficulties in adherence to a gluten-free diet. Methods for testing compliance to a gluten-free diet are costly and cumbersome. Thus, a simple biomarker of gluten intake is needed in a clinical setting and will be useful for epidemiologic studies investigating wider effects of gluten intake. OBJECTIVE: The aim was to evaluate plasma total alkylresorcinol concentrations as a measure of gluten intake. METHODS: In this randomized, controlled, crossover intervention study in 52 Danish adults with features of the metabolic syndrome, we compared 8 wk of a gluten-rich and gluten-poor diet separated by a washout period of ≥6 wk. We measured fasting plasma concentrations of alkylresorcinols to determine if they reflected differences in gluten intake as a secondary outcome of the original study. In addition, we investigated in 118 Danish adults the cross-sectional association between self-reported gluten intake and plasma alkylresorcinols in the same and a similar study at baseline. We used mixed-model ANCOVA for examining treatment effects, a classification tree to determine compliance to the gluten-poor diet, and linear regression models for examining baseline correlation between plasma alkylresorcinol concentrations and gluten intake. RESULTS: Plasma total alkylresorcinols decreased more during the gluten-poor period (geometric mean: -124.8 nmol/L; 95% CI: -156.5, -93.0 nmol/L) than in the gluten-rich period (geometric mean: -31.8 nmol/L; 95% CI: -63.1, -0.4 nmol/L) (P < 0.001). On the basis of the plasma alkylresorcinol profile, we built a classification tree to objectively determine compliance and found an overall participant misclassification error of 3.9%. In the cross-sectional study we found a 5.6% (95% CI: 2.4%, 8.9%) increase in plasma total alkylresorcinols per 1-g increase in reported gluten intake (P < 0.001). CONCLUSION: We propose the use of plasma alkylresorcinols to monitor compliance to a gluten-free diet as well as to help investigations into the possible effects of gluten in the wider population. This trial was registered at www.clinicaltrials.gov as NCT017119913 and NCT01731366.

Celiac disease.

This review will focus on the pathogenesis, clinical manifestations, diagnosis, and management of celiac disease (CD). Given an increasing awareness of gluten-related disorders, medical professionals of all varieties are encountering patients with a diagnosis of CD or who are thought to have food intolerance to gluten. The prevalence of CD among the general population is estimated to be 1% in Western nations, and there is growing evidence for underdiagnosis of the disease, especially in non-Western nations that were traditionally believed to be unaffected. The development of serologic markers specific to CD has revolutionized the ability both to diagnose and monitor patients with the disease. Additionally, understanding of the clinical presentations of CD has undergone a major shift over the past half century. Although it is well understood that CD develops in genetically predisposed subjects exposed to gluten, the extent of other environmental factors in the pathogenesis of the disease is an area of continued research. Currently, the main therapeutic intervention for CD is a gluten-free diet; however, novel nondietary agents are under active investigation. Future areas of research should also help us understand the relationship of CD to other gluten-related disorders.

Risk of congenital malformations among offspring of mothers and fathers with celiac disease: a nationwide cohort study.

BACKGROUND & AIMS: Many patients with celiac disease experience malabsorption, weight loss, and anemia; undiagnosed celiac disease during pregnancy has been linked with adverse outcomes. Studies of celiac disease and congenital malformations in offspring have been underpowered. We investigated the risk of congenital malformations among the offspring of parents with celiac disease. METHODS: We performed a nationwide cohort study of data from linked health care registers in Sweden from 1973 through 2009. We collected histopathology data from 28 pathology departments in Sweden to identify individuals with celiac disease (based on the presence of villous atrophy). We estimated the risks of malformations in the offspring of mothers and fathers with and without celiac disease. Logistic regression was used to estimate adjusted prevalence odds ratios (aPORs) with 95% confidence intervals (CIs). RESULTS: Among 11,382 offspring of mothers with celiac disease, there were 672 cases (5.9%) of malformation compared with 2098 cases (5.1%) among 40,922 offspring of mothers without celiac disease. Similarly, 352 (5.9%) of 6002 offspring of fathers with celiac disease and 1009 (5.1%) of 19,600 offspring of fathers without celiac disease had a malformation. In adjusted analyses, the offspring of mothers or fathers with celiac disease had a slightly increased risk of having children with malformations (for those with mothers with celiac disease: aPOR, 1.15; 95% CI, 1.05-1.26; for those with fathers with celiac disease: aPOR, 1.14; 95% CI, 1.00-1.29). However, these excess risks decreased or vanished entirely when we restricted our data to births since 2000 (for those with mothers with celiac disease: aPOR, 1.11; and 95% CI, 0.79-1.56; for those with fathers with celiac disease: aPOR, 1.01; 95% CI, 0.81-1.26). CONCLUSIONS: In a nationwide study, we found an increased risk for malformation among the offspring of mothers or fathers with celiac disease. However, the excess risk is small; the upper limits of the CIs for malformation indicate a 29% maximum relative increase.

Human adaptations to diet: Biological and cultural coevolution.

Modern humans evolved in Africa some 200,000 years ago, and since then, human populations have expanded and diversified to occupy a broad range of habitats and use different subsistence modes. This has resulted in different adaptations, such as differential responses to diseases and different abilities to digest or tolerate certain foods. The shift from a subsistence strategy based on hunting and gathering during the Palaeolithic to a lifestyle based on the consumption of domesticated animals and plants in the Neolithic can be considered one of the most important dietary transitions of Homo sapiens. In this text, we review four examples of gene-culture coevolution: (i) the persistence of the enzyme lactase after weaning, which allows the digestion of milk in adulthood, related to the emergence of dairy farming during the Neolithic; (ii) the population differences in alcohol susceptibility, in particular the ethanol intolerance of Asian populations due to the increased accumulation of the toxic acetaldehyde, related to the spread of rice domestication; (iii) the maintenance of gluten intolerance (celiac disease) with the subsequent reduced fitness of its sufferers, related to the emergence of agriculture and (iv) the considerable variation in the biosynthetic pathway of long-chain polyunsaturated fatty acids in native populations with extreme diets.

Knowledge of and behaviors toward a gluten-free diet among women at a health sciences university.

Purpose: Gluten-free diets have gained popularity worldwide. However, little information is available regarding the knowledge of, and behaviors toward, this diet among adults in KSA. This study was aimed at addressing this knowledge gap. Methods: A cross-sectional survey was conducted in 352 women at a health sciences university in KSA. Results: Eleven percent of participants had followed a gluten-free diet at least once, 70% of whom had voluntarily tried this diet without a confirmed medical diagnosis. The main source of information regarding this diet was the internet and social media. Additionally, followers of this diet had moderate knowledge of gluten and its products yet higher knowledge than that of non-followers (65% vs 56%, P = .0055). Following a GFD was associated with an age of 25 years or older, higher education, and being employed. Although 56% of participants reported following this diet 75% or more of the time, the average calculated adherence score was low. Although 95% of the followers indicated changes in their lifestyle and social life, 71% felt better after following this diet, and only 2.6% felt worse. This self-reported results were confirmed by a calculated average quality of life score of 1.3, indicating a good quality of life after following this diet. Conclusion: This study indicated moderate knowledge and low adherence to a gluten-free diet among followers. This finding may be attributable to the high percentage of followers without a confirmed medical condition, or to the social and lifestyle changes faced by followers of GFDs. Educational programs should be introduced to the public to increase awareness of gluten-free foods and diets.

Gluten Intolerance and Its Association With Skin Disorders: A Narrative Review.

Gluten sensitivity is defined as a chronic intolerance to gluten ingestion in genetically predisposed individuals. The etiology is thought to be immune-mediated and has a variable dermatologic presentation. Celiac disease (CD) is one of the most common forms of gluten intolerance and encompasses a wide range of extra-intestinal pathology, including cutaneous, endocrine, nervous, and hematologic systems. Psoriasis, another long-term inflammatory skin condition, has been linked to significant symptomatic improvement with a gluten-free diet (GFD). Palmoplantar pustulosis (PP), a variant of psoriasis, and aphthous stomatitis, which causes recurrent oral ulcers, have also exhibited beneficial results after the dietary elimination of gluten. In addition to this, dermatitis herpetiformis (DH), another immune-mediated skin disorder, is genetically similar to CD and has, therefore, shown tremendous improvement with a GFD. Another highly prevalent long-term skin condition called atopic dermatitis (AD), however, has revealed inconsistent results with gluten elimination and would require further research in the future to yield concrete results. Hereditary angioedema (HA) has shown an association with gluten intolerance in some patients who had symptomatic benefits with a GFD. Similarly, vitiligo and linear IgA bullous dermatosis have also shown some clinical evidence of reversal with a GFD. On the contrary, rosacea enhances the risk of developing CD. This narrative review emphasizes the potential impact of gluten intolerance on different cutaneous conditions and the potential therapeutic effect of a GFD on various symptomatic manifestations. There is a need for additional clinical and observational trials to further expand on the underlying pathophysiology and provide conclusive and comprehensive recommendations for possible dietary interventions.

Self-reported food intolerances in an Indian population: Need for individualization rather than a universal low-FODMAP diet.

Background and Aim: Low-fermentable oligo-, di-, and monosaccharides and polyol (FODMAP) diets have been recommended for individuals with food intolerance and irritable bowel syndrome (IBS). Individual food intolerances may, however, not correspond to the FODMAP content alone. Methods: We conducted a survey on self-reported intolerance to articles of food commonly identified as high FODMAP in 400 healthy Indian subjects (median age 40 years; 69% men) and 204 consecutive consenting patients with IBS (median age 36 years; 58% men). Results: One-hundred seventy-nine (44.8%) healthy subjects and 147 (72.1%) patients with IBS reported some food intolerance (P < 0.00001); the latter reported intolerance to all items (except nuts) more frequently than healthy subjects. The prevalence, however, varied from 2.5 to 32%. Milk intolerance was reported equally commonly by healthy subjects and patients (23% vs 29.9%). Twenty-three (11.3%) patients and no healthy subjects reported wheat sensitivity. The IBS diarrhea subgroup reported intolerance to milk, pulses, capsicum, cauliflower, leafy vegetables, and dry fruits more frequently than the constipation subgroup. Conclusion: From among a list of high-FODMAP items, individuals' intolerance varied widely, suggesting that individuals should be the final judge in deciding their elimination diets rather than devise them based on the FODMAP content alone. As in the West, food intolerance was reported more commonly by patients with IBS, especially those with diarrhea, than by healthy individuals. Also noteworthy is the low prevalence of milk intolerance in a subcontinent labeled as high in lactose intolerance. Unlike in the West, wheat intolerance was not reported by any healthy individual.

Identification and Growth Characteristics of a Gluten-Degrading Bacterium from Wheat Grains for Gluten-Degrading Enzyme Production.

Immunogenic peptides from wheat gluten can be produced during digestion, which are difficult to digest by gastrointestinal proteases and negatively affect immune responses in humans. Gluten intolerance is a problem in countries where wheat is a staple food, and a gluten-free diet is commonly recommended for its treatment and prevention. Enzyme approaches for degradation of the peptides can be considered as a strategy for its prevention. Here, we isolated a gluten-degrading bacterium, Bacillus amyloliquefaciens subsp. plantarum, from wheat grains. The culture conditions for enzyme production or microbial use were considered based on gluten decomposition patterns. Additionally, the pH range for the activity of the crude enzyme was investigated. The bacterium production of gluten-degrading enzymes was temperature-dependent within 25 °C to 45 °C, and the production time decreased with increasing culture temperature. However, it was markedly decreased with increasing biofilm formation. The bacterium decomposed high-molecular-weight glutenin proteins first, followed by gliadin proteins, regardless of the culture temperature. Western blotting with an anti-gliadin antibody revealed that the bacterium decomposed immunogenic proteins related to α/ß-gliadins. The crude enzyme was active in the pH ranges of 5 to 8, and enzyme production was increased by adding gliadin into the culture medium. In this study, the potential of the B. amyloliquefaciens subsp. plantarum for gluten-degrading enzyme production was demonstrated. If further studies for purification of the enzyme specific to the immunogenic peptides and its characteristics are conducted, it may contribute as a strategy for prevention of gluten intolerance.

Frequency of Celiac Disease in Patients With Chronic Diarrhea.

INTRODUCTION: Celiac disease (CD) is an immune-mediated disease caused by ingesting gluten-containing foods and is characterized mainly by malabsorptive diarrhea. Furthermore, distinguishing between mild disease and asymptomatic individuals is critical and necessitates a high level of clinical suspicion. Short stature, delayed puberty, bone abnormalities, neurological problems, and intestinal cancer can all be consequences of a delayed diagnosis. This study aimed to determine the prevalence of celiac disease among our community's recurrent diarrhea patients. METHODS: This was a cross-sectional study aimed at determining the frequency of celiac disease in patients with chronic diarrhea. One hundred eighty-eight patients between the ages of 18 and 60 years who had chronic diarrhea lasting greater than three months were enrolled in this study. Stratification was utilized to control for modifiers. A p-value of ≤ 0.05 was considered significant. RESULTS: A total of 74.5% of patients (n=140) were male, while 25.5% (n=48) were female with a mean age of 38.48±10.85 years. The average duration of celiac disease symptoms was 8.17± 3.75 months. Celiac disease was found in 12.2% (n=23) of the individuals. Also, 21% of individuals with a positive family history of CD devolved CD, compared to those without prior CD family history (p=0.01). CONCLUSIONS: In individuals with chronic diarrhea for more than three months, the prevalence of celiac disease was determined to be 12.2% (n=23). There was a statistically significant difference between those with a positive family history of CD and those who did not have the condition.