How does a celiac iceberg really float? The relationship between celiac disease and gluten.

Celiac disease (CD) is an autoimmune intestinal disease caused by intolerance of genetically susceptible individuals after intake of gluten-containing grains (including wheat, barley, etc.) and their products. Currently, CD, with "iceberg" characteristics, affects a large population and is distributed over a wide range of individuals. This present review summarizes the latest research progress on the relationship between CD and gluten. Furthermore, the structure and function of gluten peptides related to CD, gluten detection methods, the effects of processing on gluten and gluten-free diets are emphatically reviewed. In addition, the current limitations in CD research are also discussed. The present work facilitates a comprehensive understanding of CD as well as gluten, which can provide a theoretical reference for future research.

Bi-directional Relationship Between Celiac Disease and Liver Chemistries: A Systematic Review and Meta-Analysis.

AIMS: Previous studies have reported conflicting results regarding prevalence of elevated LC (2-70%) in celiac disease (CD). This systematic review and meta-analysis assessed the prevalence of elevated LC at time of CD diagnosis and associated response to GFD. We also report the prevalence of CD in patients with unexplained elevation of LC. METHODS: Studies assessing LC (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) in CD patients were eligible. Studies with < 50 cases or in pediatric populations were excluded. RESULTS: In total, 20 studies assessing prevalence of elevated LC in 4,265 participants with newly diagnosed CD (mean age = 35.6 ± 6.5 years, 69.8% female) were included. Pooled prevalence of elevated LC was 18.7% (95% CI 13.8-24.8; I2 = 95%). Normalization of elevated LC was seen in 83.1% (95% CI 73.4-89.7; I2 = 79%, 11 studies) of patients after GFD. On meta-regression, age at CD diagnosis, gender, and Marsh grading were not associated with elevated LC. Among 979 participants (7 studies) with unexplained elevation of LC, pooled seroprevalence and biopsy-proven CD was 6.4% (95% CI 2.9-10.3, I2 = 71%) and 4.5% (95% CI 2.6-7.7, I2 = 67%), respectively. CONCLUSION: Elevated LC are seen in approximately one-fifth of patients at CD diagnosis with majority normalizing after GFD. Age, gender, and degree of intestinal damage are not predictive of elevated LC. In the appropriate clinical scenario, liver tests should be serially monitored in CD reserving workup for additional causes after a trial of GFD. Patients with unexplained elevation of liver tests should be screened for celiac disease.

Plasma IL-2 and Symptoms Response after Acute Gluten Exposure in Subjects With Celiac Disease or Nonceliac Gluten Sensitivity.

INTRODUCTION: Treated patients with celiac disease (CeD) and nonceliac gluten sensitivity (NCGS) report acute, transient, incompletely understood symptoms after suspected gluten exposure. To determine whether (i) blinded gluten exposure induces symptoms, (ii) subjects accurately identify gluten exposure, and (iii) serum interleukin-2 (IL-2) levels distinguish CeD from NCGS subjects after gluten exposure. METHODS: Sixty subjects (n = 20 treated, healed CeD; n = 20 treated NCGS; n = 20 controls) were block randomized to a single, double-blind sham (rice flour) or 3-g gluten challenge with 72-hours follow-up. Twelve serial questionnaires (100 mm visual analog scale; pain, bloating, nausea, and fatigue) and 10 serial plasma samples were collected. Mucosal permeability was assessed using both urinary lactulose-13C mannitol ratios and endoscopic mucosal impedance. RESULTS: Thirty-five of 40 (83%) subjects with CeD and NCGS reported symptoms with gluten (8 CeD, 9 NCGS) and sham (9 CeD, 9 NCGS) compared with 9 of 20 (45%) controls after gluten (n = 6) and sham (n = 3). There was no significant difference in symptoms among groups. Only 2 of 10 subjects with CeD and 4 of 10 NCGS identified gluten, whereas 8 of 10 subjects with CeD and 5 of 10 NCGS identified sham. A significant plasma IL-2 increase occurred only in subjects with CeD after gluten, peaking at 3 hours and normalizing within 24 hours postchallenge despite no significant intestinal permeability change from baseline. DISCUSSION: Symptoms do not reliably indicate gluten exposure in either subjects with CeD or NCGS. IL-2 production indicates a rapid-onset gluten-induced T-cell activation in CeD despite long-standing treatment. The effector site is unknown, given no increased intestinal permeability after gluten.

Biomarkers for the diagnosis and monitoring of celiac disease: can you count on me?

PURPOSE OF REVIEW: Different markers are available to diagnose and monitor celiac disease (CeD); however, the concordance among them and their efficacy are still controversial. We aim at defining the efficacy of CeD biomarkers, their advantages and limits. RECENT FINDINGS: CeD diagnostic criteria are widely accepted, being a positive serology and duodenal atrophy (according to the Marsh-Oberhuber score) the main hallmarks. Flow cytometry and other molecular biomarkers support the diagnosis of refractory CeD. On the other side, CeD monitoring is less defined, as the biomarkers are not always reliable. To date, the reference standard to detect mucosal healing is represented by duodenal histology, but its timing and significance are debated. Novel scores may better define the trend of mucosal damage and MicroRNAs are among the innovative noninvasive biomarkers. The assessment of a correct gluten-free diet (GFD) is another aspect of CeD monitoring, based upon questionnaires and recently developed tools such as dosage of urinary or faecal gluten immunogenic peptides. SUMMARY: Clinicians lack of a widely acknowledged tools to monitor CeD and GFD. Here, we present the efficacy of the most used markers.

Enteric-Release Budesonide May Be Useful in the Management of Non-Responsive Celiac Disease.

BACKGROUND: Non-responsive celiac disease (NRCD) has many aetiologies, including gluten exposure. Budesonide may be used for refractory celiac disease (RCD) and celiac crisis. AIMS: We reviewed the effectiveness of budesonide to induce clinical and histologic response in NRCD with villous atrophy (VA). METHODS: Case series of adult cases with NRCD and VA prescribed budesonide at two celiac centers. Clinical variables and mucosal recovery (i.e., normal villous architecture within 1 year of treatment) were evaluated. RESULTS: Forty-two cases [77% female, median age 45.0 (IQR 28.3-60.0) years] were included. Most common symptoms were diarrhea (64%) and abdominal pain (62%). Budesonide was initiated at 9 mg (83%) for a median duration of 16.0 weeks (IQR 6.8-25.0 weeks). In total, 57% exhibited a clinical response, positively associated with diarrhea (adjusted OR 6.08 95% CI 1.04-35.47) and negatively with fatigue (adjusted OR 0.18 95% CI 0.03-0.98). Clinical response was higher among those with dietitian counseling prior to budesonide (n = 29, 70 vs. 23%, p < 0.01). Mucosal recovery was observed in 11/24 with follow-up duodenal biopsies. There was no association between clinical response and mucosal recovery, and 79% of clinical responders had a symptomatic relapse. RCD (48%) and chronic gluten exposure (24%) were the main suspected aetiologies of NRCD. Most individuals without a clinical response subsequently received an IBS-related diagnosis. CONCLUSIONS: Budesonide may be effective to induce clinical response in NRCD presenting with diarrhea and VA, but clinical recurrence and lack of mucosal recovery are frequent after tapering. Other diagnoses, including coexisting IBS, may be considered in non-responders to budesonide therapy.

Gynecological Disorders in Patients with Non-celiac Wheat Sensitivity.

BACKGROUND: Non-celiac wheat sensitivity (NCWS) most frequently presents clinically with irritable bowel syndrome (IBS)-like symptoms, although many extra-intestinal manifestations have also been attributed to it. No studies to date have evaluated the presence and frequency of gynecological symptoms in NCWS. AIM: To evaluate the frequency of gynecological disorders in patients with NCWS. PATIENTS AND METHODS: Sixty-eight women with NCWS were included in the study. A questionnaire investigating gynecological symptoms and recurrent cystitis was administered, and patients reporting symptoms were then examined by specialists. Three control groups were selected: 52 patients with IBS not related to NCWS, 56 patients with celiac disease (CD), and 71 healthy controls. RESULTS: 59% of the patients with NCWS showed gynecological symptoms, a higher frequency than in healthy controls (P = 0.04), IBS controls (P = 0.01) and CD controls (P = 0.02). Menstrual cycle alterations were more frequent in patients with NCWS than in healthy controls (26.5% vs 11.3%; P = 0.03); the patients with NCWS suffered from recurrent vaginitis (16%) and dyspareunia (6%) significantly more frequently than healthy controls. Twenty-nine percent of patients with NCWS reported recurrent cystitis, a finding higher than in the control groups (vs healthy P = 0.0001, vs IBS P = 0.001, vs CD controls P = 0.04). Microbiological examinations were negative in most of the patients with NCWS and recurrent vaginitis or cystitis. During the 1-year follow-up, 46% of patients with menstrual disorders and 36% with recurrent vaginitis reported resolution of symptoms on a wheat-free diet. CONCLUSIONS: Patients with NCWS showed a significantly higher frequency of gynecological symptoms and recurrent cystitis than patients with IBS.

Lactobacilli Degrade Wheat Amylase Trypsin Inhibitors to Reduce Intestinal Dysfunction Induced by Immunogenic Wheat Proteins.

BACKGROUND & AIMS: Wheat-related disorders, a spectrum of conditions induced by the ingestion of gluten-containing cereals, have been increasing in prevalence. Patients with celiac disease have gluten-specific immune responses, but the contribution of non-gluten proteins to symptoms in patients with celiac disease or other wheat-related disorders is controversial. METHODS: C57BL/6 (control), Myd88-/-, Ticam1-/-, and Il15-/- mice were placed on diets that lacked wheat or gluten, with or without wheat amylase trypsin inhibitors (ATIs), for 1 week. Small intestine tissues were collected and intestinal intraepithelial lymphocytes (IELs) were measured; we also investigated gut permeability and intestinal transit. Control mice fed ATIs for 1 week were gavaged daily with Lactobacillus strains that had high or low ATI-degrading capacity. Nonobese diabetic/DQ8 mice were sensitized to gluten and fed an ATI diet, a gluten-containing diet or a diet with ATIs and gluten for 2 weeks. Mice were also treated with Lactobacillus strains that had high or low ATI-degrading capacity. Intestinal tissues were collected and IELs, gene expression, gut permeability and intestinal microbiota profiles were measured. RESULTS: In intestinal tissues from control mice, ATIs induced an innate immune response by activation of Toll-like receptor 4 signaling to MD2 and CD14, and caused barrier dysfunction in the absence of mucosal damage. Administration of ATIs to gluten-sensitized mice expressing HLA-DQ8 increased intestinal inflammation in response to gluten in the diet. We found ATIs to be degraded by Lactobacillus, which reduced the inflammatory effects of ATIs. CONCLUSIONS: ATIs mediate wheat-induced intestinal dysfunction in wild-type mice and exacerbate inflammation to gluten in susceptible mice. Microbiome-modulating strategies, such as administration of bacteria with ATI-degrading capacity, may be effective in patients with wheat-sensitive disorders.

Synthetic Neoepitopes of the Transglutaminase-Deamidated Gliadin Complex as Biomarkers for Diagnosing and Monitoring Celiac Disease.

BACKGROUND & AIMS: Celiac disease (CeD) has characteristics of an autoimmune disease, such as increased antibody levels to tissue transglutaminase (tTG). However, assays to measure these biomarkers in blood samples do not identify patients with sufficient accuracy for diagnosis or monitoring of CeD. We aimed to discover biomarkers of CeD derived from neoepitopes of deamidated gliadin peptides (DGP) and tTG fragments and to determine if immune reactivity against these epitopes can identify patients with CeD with mucosal healing. METHODS: We analyzed serum samples from 90 patients with biopsy-proven CeD and 79 healthy individuals (controls) for immune reactivity against the tTG-DGP complex (discovery cohort). A fluorescent peptide microarray platform was used to estimate the antibody-binding intensity of each synthesized tTG-DGP epitope. We validated our findings in 82 patients with newly diagnosed CeD and 217 controls. We tested the ability of our peptide panel to identify patients with mucosal healing (based on the histologic analysis) using serum samples from patients with treated and healed CeD (n = 85), patients with treated but unhealed CeD (n = 81; villous atrophy despite a adhering a gluten-free diet), patients with untreated CeD (n = 82) and disease controls (n = 27), villous atrophy without CeD), and healthy controls (n = 217). Data were analyzed using principal component analysis followed by machine learning and support vector machine modeling. RESULTS: We identified 172 immunogenic epitopes of the tTG-DGP complex. We found significantly increased immune reactivity against these epitopes vs controls. In the both cohort, the set of neoepitopes derived from the tTG-DGP complex identified patients with CeD with 99% sensitivity and 100% specificity. Serum samples from patients with untreated CeD had the greatest mean antibody-binding intensity against the tTG-DGP complex (32.5 ± 16.4). The average antibody-binding intensity was significantly higher in serum from patients with treated but unhealed CeD mucosa (15.1 ± 7.5) than in patients with treated and healed CeD mucosa (5.5 ± 3.4) (P < .001). The assay identified patients with mucosa healing status with 84% sensitivity and 95% specificity. CONCLUSIONS: We identified immunogenic epitopes of the tTG-DGP complex, and found that an assay to measure the immune response to epitopes accurately identified patients with CeD, as well as patients with mucosal healing. This biomarker assay might be used in detection and monitoring of patients with CeD.

Noncoeliac wheat sensitivity and diet.

PURPOSE OF REVIEW: Noncoeliac gluten sensitivity (NCGS) can be suspected after exclusion of coeliac disease and wheat allergy. However, poorly understood pathogenesis of the NCGS, lack of gold standard for diagnosis and agreement in the definition for the NCGS condition, open the space for future investigation. This review aims to give an overview on the diagnosis and effective diet composition in the treatment of NCGS symptoms. RECENT FINDINGS: It appears that a diet low in fermentable oligo, di, and monosaccharides and polyols (FODMAPs) and gluten-free diet play a prominent role in the strategy of NCGS management. Considering available evidence with respect to diagnostic tools, it is challenging to prepare a standard guideline for NCGS diagnosis and treatment with clear cut-offs for symptom reduction/improvement that could directly be translated into test results. Nutritional support, including the use of pre/probiotics, has to be tailored to the individual situation of NCGS patients. SUMMARY: The exclusion of such components of wheat as amylase/trypsin inhibitors, wheat-germ agglutinins, or free of FODMAPs diet can reduce clinical symptoms of NCGS. The further investigation on microbiota changes may strengthen the knowledge in this area, where the major challenge is to develop biomarkers for NCGS investigation.

Withdrawing gluten-free food from prescriptions in England: a mixed-methods study to examine the impact of policy changes on quality of life.

BACKGROUND: Some local areas in England stopped have gluten-free prescriptions for coeliac disease. An explanatory mixed-methods study has investigated the impact of these changes. METHODS: A cross-sectional survey with 1697 participants was followed by 24 qualitative interviews. The survey included questions on the use of prescriptions and healthcare services, as well as the Coeliac Disease Assessment Questionnaire (CDAQ) to assess quality of life. The survey data were analysed by descriptive statistics, analysis of variance and regression analysis, and the interviews were analysed by thematic analysis. Findings from the interviews guided the survey analysis. RESULTS: Dietary burden was significantly different between prescribing and nonprescribing areas, with little impact on other aspects of quality of life. Survey participants in nonprescribing areas who felt more impacted by the prescription changes reported a lower quality of life. Satisfaction with and use of services was lower in nonprescribing areas. Interviews indicated that, after initial frustrations, most people adapted to the changed prescription policy. However, there was a clear preference for gluten-free prescriptions to be available, in particular for staple foods. CONCLUSIONS: The main quality of life impact was on Dietary burden. It is encouraging that most participants in the present study maintained a good quality of life. However, issues of worse experiences of care, lower follow-up opportunities and inequity arose, and these should be taken into consideration in decisions on gluten-free food prescriptions. The new guidelines for the National Health Service in England have retained prescriptions for bread and flour mixes, which is more limited than the range of staple foods preferred in the present study.

Influence of nutrition education in paediatric coeliac disease: impact of the role of the registered dietitian: a prospective, single-arm intervention study.

BACKGROUND: The diagnosis of coeliac disease (CD) involves a change in the diet of the individual, which may influence their quality of life and nutritional status. The present study aimed to determine whether nutrition education by a registered dietitian is able to improve eating habits and body composition in children with CD. METHODS: Dietary, physical activity and body composition changes were analysed, comparing baseline assessments with those 1 year after receiving education on healthy eating. At both time points, a 3-day dietary survey, a food frequency consumption questionnaire, an adherence to the Mediterranean diet test (Kidmed), duration of activity and an electrical bioimpedance study were conducted. Student's paired t-test and the McNemar test were also employed. RESULTS: Seventy-two subjects (42 girls) with an mean (range) age of 10 (2-16) years were included. Before the intervention, an unbalanced diet was observed, rich in protein and fat, and deficient in complex carbohydrates. Only 14% consumed an adequate Mediterranean diet. After nutrition intervention, a significant increase in the consumption of plant-based foods and a concomitant decrease in meat, dairy and processed food intake (P < 0.001) were observed. Moreover, 92% of the patients (P < 0.001) managed to consume an adequate Mediterranean diet. Similarly, an increase was observed in the duration of physical activity undertaken [mean (SD) 1.02 (1.79) h, P < 0.001] and improvements in body composition were recorded, with a 17% decrease in fat mass percentage (P < 0.001). CONCLUSIONS: Nutrition intervention focused on healthy eating is effective with respect to improving the nutritional status and diet quality in CD patients.

Thiol-disulfide homeostasis in children with celiac disease.

BACKGROUND: Toxic gliadin peptide damages enterocytes in celiac disease by causing oxidative stress. Thiols are organic compounds that defend against oxidative stress. This study aimed to investigate the changes in thiol-disulfide homeostasis in children with celiac disease. METHODS: The study included patients with celiac disease, children diagnosed with functional gastrointestinal disorders, and healthy children. Patients' serum native and total thiol-disulfide amounts, disulfide/total thiol percentage ratios, disulfide / native thiol percentage ratios, and native thiol/total thiol percentage ratios were measured. RESULTS: The study involved 172 children, of whom 90 (52.3%) were girls. The mean participant age was 8.6 ± 4.2 years. A total of 59 (34.3%) children had celiac disease, 56 (32.6%) had functional gastrointestinal disorders, and 57 (33.1%) were healthy. The total thiol and disulfide levels of patients with celiac disease (305 ± 87 µmol/L and 25 ± 15 µmol/L, respectively) were significantly lower than those of healthy children (349 ± 82 µmol/L and 40 ± 15 µmol/L, respectively) (P = 0.006 and P < 0.001, respectively). Native and total thiol levels (226 ± 85 µmol/L and 279 ± 99 µmol/L, respectively) in patients with celiac disease who consumed a gluten-containing diet were significantly lower than those of patients who consumed a gluten-free diet (278 ± 64 µmol/L and 327 ± 69 µmol/L, respectively) (P = 0.017 and P = 0.041, respectively). CONCLUSIONS: Thiol-disulfide homeostasis, an important antioxidant defense component of the gastrointestinal system, is disrupted in children with celiac disease. A gluten-free diet helped partially ameliorate this decline.

Dietary Gluten and Neurodegeneration: A Case for Preclinical Studies.

Although celiac disease (CD) is an autoimmune disease that primarily involves the intestinal tract, mounting evidence suggests that a sizeable number of patients exhibit neurological deficits. About 40% of the celiac patients with neurological manifestations have circulating antibodies against neural tissue transglutaminase-6 (tTG6). While early diagnosis and strict adherence to a gluten-free diet (GFD) have been recommended to prevent neurological dysfunction, better therapeutic strategies are needed to improve the overall quality of life. Dysregulation of the microbiota-gut-brain axis, presence of anti-tTG6 antibodies, and epigenetic mechanisms have been implicated in the pathogenesis. It is also possible that circulating or gut-derived extracellular structures and including biomolecular condensates and extracellular vesicles contribute to disease pathogenesis. There are several avenues for shaping the dysregulated gut homeostasis in individuals with CD, non-celiac gluten sensitivity (NCGS) and/or neurodegeneration. In addition to GFD and probiotics, nutraceuticals, such as phyto and synthetic cannabinoids, represent a new approach that could shape the host microbiome towards better prognostic outcomes. Finally, we provide a data-driven rationale for potential future pre-clinical research involving non-human primates (NHPs) to investigate the effect of nutraceuticals, such as phyto and synthetic cannabinoids, either alone or in combination with GFD to prevent/mitigate dietary gluten-induced neurodegeneration.

The Impact of a Gluten-Free Diet on Celiac Disease: A Comprehensive Evaluation of Two Cases Using NIH Patient Reported Outcome Measures (PROMIS, NTCB, and Neuro-QoL).

The aim of this study is to demonstrate the effectiveness of the gluten-free diet (GFD) for celiac disease (CD) in a multidisciplinary outpatient Gastroenterology clinic with two adult cases using the innovative, paradigm-shifting measurement systems: The NIH Patient reported outcome measures (PROs). CD results in gastrointestinal (GI) dysfunction, but is also associated with other inflammatory responses, psychosocial impairment, and cognitive deficits such as "brain fog." Adherence to the GFD for 6 months was associated with improvement in specific GI symptoms in one case (PROMIS-GI; Case 2) and improvement in cognitive functioning (NIH Toolbox Cognitive Battery) and psychosocial functioning (Neuro-QOL) in both cases. Notably, improvement in cognitive flexibility occurred in both younger and an older adult patient. This suggests that cognitive decline and the psychosocial deficits associated with CD are reversible with GFD. The NIH PROs were found to be effective, sensitive to change, and minimally disruptive to clinic operations.

Coeliac disease presenting with chorea.

Chorea can be genetic or acquired, and often leads to a challenging diagnostic conundrum. In a significant proportion, there is no specific identifiable cause. Chorea is a rare but potentially reversible neurological manifestation of coeliac disease, usually presenting insidiously and often presumed to be associated with typical gastrointestinal symptoms. We report a patient with rapidly progressive generalised chorea, but without preceding gastrointestinal symptoms, who was subsequently diagnosed with coeliac disease. A gluten-free diet resulted in complete resolution of the chorea.

Prevalence of Adverse Reactions to Gluten and People Going on a Gluten-Free Diet: A Survey Study Conducted in Brazil.

BACKGROUND: The prevalence of gluten-related disorders (GRD) and adherence to a gluten-free diet (GFD) remains unknown in Brazilian population and there is no published information on the scientific literature about the proportion of Brazilians that were diagnosed with a gluten-related disorder. Thus, the aim of this work was to estimate the prevalence of GRDs and adherence to a GFD by self-report in adult Brazilian population. MATERIALS AND METHODS: A questionnaire-based cross-sectional study was conducted in two Brazilian cities. RESULTS: The response rate was 93.2% (1630/1749). The self-reported prevalence rates were (95% CI): adverse reactions to gluten 10.06% (8.64-11.62); gluten sensitivity 2.33% (1.65-3.18); physician-diagnosed celiac disease 0.3% (0.09-0.71); non-celiac gluten sensitivity 1.71% (1.14-2.47); wheat allergy 0.79% (0.42-1.36); adherence to gluten-free diet 7.48% (6.25-8.87); gluten avoiders 15.21% (13.5-17.05). Among those who were following a GFD (n = 122), 65.6% (n = 80) of them reported that they did not develop symptoms after wheat/gluten ingestion and 50% (n = 61) were following the diet without medical/dietitian advice. The main motivation for following a GFD in the self-reported and non-self-reported gluten sensitivity groups were the symptoms triggered after wheat/gluten ingestion (86.8%) and weight control (57.1%), respectively. CONCLUSIONS: Implementation of programs to increase awareness about GRDs among healthcare professionals and giving scientifically sound information to the general population about the risks and benefits for following a GFD are desirable actions in Brazil. The results also add to the growing body of evidence for highlighting the under-diagnosis of GRD and the trend for following a GFD in Latin America.

Metabolic interventions in Autism Spectrum Disorder.

Metabolic interventions including special diets and supplements are commonly used in Autism Spectrum Disorder (ASD). Yet little is known about how these interventions, typically initiated by caregivers, may affect metabolic function or the core symptoms of ASD. This review examines possible direct and indirect roles for metabolism in the core symptoms of ASD as well as evidence for metabolic dysfunction and nutritional deficiencies. We also discuss some of the most popular diets and supplements used in our patient population and suggest strategies for discussing the utility of these interventions with patients, families, and caregivers.

Dietary Patterns After the Weaning and Lactation Period Are Associated With Celiac Disease Autoimmunity in Children.

BACKGROUND & AIMS: There have been many studies of associations between infant feeding practices and development of celiac disease during childhood, but few studies have focused on overall diets of young children after the weaning period. We aimed to examine the association between common dietary patterns in infants and the occurrence of celiac disease autoimmunity during childhood. METHODS: We performed a prospective analysis of data from the Generation R Study that comprised 1997 children born from April 2002 through January 2006 in Rotterdam, the Netherlands. Food consumption around 1 year of age was assessed with a validated food-frequency questionnaire. Dietary data were examined using a priori (based on existing guidelines) and a posteriori (principal component analysis and reduced rank regression) dietary pattern analyses. Five dietary patterns were compared. Celiac disease autoimmunity, determined on the basis of serum concentration of transglutaminase-2 autoantibody (ie, TG2A) below or above 7 U/mL, was evaluated at 6 years. Associations between dietary pattern adherence scores and celiac disease autoimmunity were examined using multivariable logistic regression models. RESULTS: Higher adherence to the a posteriori-derived prudent dietary pattern (high intake of vegetables, vegetable oils, pasta, and grains and low consumption of refined cereals and sweet beverages) at 1 year was significantly associated with lower odds of celiac disease autoimmunity at 6 years (odds ratio, 0.67; 95% confidence interval, 0.53-0.84). No significant associations were found for the 4 remaining dietary patterns. CONCLUSIONS: In a prospective study of dietary patterns of young children in the Netherlands, we associated a dietary pattern characterized by high consumption of vegetables and grains and low consumption of refined cereals and sweet beverages, with lower odds of celiac disease autoimmunity. Early-life dietary patterns might therefore be involved in the development of celiac disease during childhood.

Promotion of Testing for Celiac Disease and the Gluten-Free Diet Among Complementary and Alternative Medicine Practitioners.

INTRODUCTION: We identified the frequency and assessed the validity of marketing claims made by American chiropractors, naturopaths, homeopaths, acupuncturists, and integrative medicine practitioners relating to the diagnosis and treatment of celiac disease and nonceliac gluten sensitivity (NCGS), both of which have increased in prevalence in recent years. METHODS: We performed a cross-sectional study analyzing websites of practitioners from 10 cities in the United States and analyzed the websites for any mention of celiac or NCGS as well as specific claims of ability to diagnose, ability to treat, and treatment efficacy. We classified treatments promoted as true, false, or unproven, as assessed independently by 2 authors. RESULTS: Of 500 clinics identified, 178 (35.6%) made a claim regarding celiac disease, NCGS, or a gluten-free diet. Naturopath clinic websites have the highest rates of advertising at least one of diagnosis, treatment, or efficacy for celiac disease (40%), followed by integrative medicine clinics (36%), homeopaths (20%), acupuncturists (14%), and chiropractors (12%). Integrative medicine clinics have the highest rates of advertising at least one of diagnosis, treatment, or efficacy for NCGS (45%), followed by naturopaths (37%), homeopaths (14%), chiropractors (14%), and acupuncturists (10%). A geographic analysis yielded no significant variation in marketing rates among clinics from different cities. Of 232 marketing claims made by these complementary and alternative medicine (CAM) clinic websites, 138 (59.5%) were either false or unproven. DISCUSSION: A significant number of CAM clinics advertise diagnostic techniques or treatments for celiac disease or NCGS. Many claims are either false or unproven, thus warranting a need for increased regulation of CAM advertising to protect the public.

Online education for gluten-free diet teaching: Development and usability testing of an e-learning module for children with concurrent celiac disease and type 1 diabetes.

BACKGROUND AND OBJECTIVE: Celiac disease (CD), the most common genetically-based food intolerance, affects 3% to 16% of children with type 1 diabetes (T1D). Treatment involves lifelong adherence to a gluten-free diet (GFD). Individualized dietary education is resource-intensive. We, therefore, sought to develop and test the usability of an e-learning module aimed at educating patients and caregivers regarding implementation of the GFD in children with concurrent CD and T1D. METHODS: An interactive e-learning module was developed based on extensive review of CD, T1D, and educational literature. A mixed-methods usability testing approach was used to refine and evaluate the module, using qualitative semi-structured interviews, observations, and satisfaction and knowledge questionnaires in two iterative cycles. The module was refined based on themes identified from each usability cycle. RESULTS: Eighteen patients (8 in cycle 1, 10 in cycle 2) and 15 caregivers (7 in cycle 1, 8 in cycle 2) participated. Patient participants had CD and T1D for a mean (SD) of 6.1 ± 5.1 and 8.3 ± 5.5 years, respectively. Their mean age was 13.5 ± 4.5 years. Thematic analysis of usability interviews showed the module to be appealing and resulted in minor module revisions after each cycle to improve usability. Mean satisfaction scores post-module completion were high (4.67 ± 0.54), indicating participants were "very satisfied" with the education. Knowledge test scores increased significantly from pre- to post-module completion (P = 0.001). CONCLUSION: A multifaceted user-centered usability approach demonstrated that an innovative, interactive e-learning module is effective in knowledge retention and can provide comprehensive and accessible information in the implementation of the GFD teaching in children with CD and T1D.