Gluten-Free Diet and Other Celiac Disease Therapies: Current Understanding and Emerging Strategies.

A lifelong gluten-free diet (GFD) is the only treatment for celiac disease and other gluten-related disorders. Nevertheless, strict adherence to the GFD is often challenging due to concerns about social isolation, risk of gluten contaminations, high cost, poor quality and the taste of gluten-free products. Moreover, although the GFD is effective in achieving mucosal healing, it may lead to dietary imbalances due to nutrient deficiencies over a long period of time. To overcome these issues, several gluten-free wheat flours have been developed to create products that closely resemble their gluten-containing counterparts. Furthermore, given the critical importance of adhering to the GFD, it becomes essential to promote adherence and monitor possible voluntary or involuntary transgressions. Various methods, including clinical assessment, questionnaires, serology for celiac disease, duodenal biopsies and the detection of Gluten Immunogenic Peptides (GIPs) are employed for this purpose, but none are considered entirely satisfactory. Since adherence to the GFD poses challenges, alternative therapies should be implemented in the coming years to improve treatment efficacy and the quality of life of patients with celiac disease. The aim of this narrative review is to explore current knowledge of the GFD and investigate its future perspectives, focusing on technology advancements, follow-up strategies and insights into a rapidly changing future.

Division of Responsibility in Child Feeding and Eating Competence: A Cross-Sectional Study in a Sample of Caregivers of Brazilian Children with Celiac Disease.

The objective of this cross-sectional study was to assess eating competence (EC) and the adherence to the division of responsibility in child feeding (sDOR) of Brazilian caregivers of children with celiac disease (CD). It also examined the association between EC and sDOR, children's adherence to a gluten-free diet, and sociodemographic data. This study administered a survey set that included sociodemographic data, health-related data, eating habits, and the instruments ecSI2.0TMBR and sDOR.2-6yTM BR, validated for a Brazilian population. The sample comprised 50 caregivers of children with CD (between 24 and 72 months of age). The participants following a gluten-free diet (GFD) presented higher scores for all EC domains and the total EC. The total EC scores were higher for the participants over 40 y/o, frequently having meals as a family, with their children consuming more than three servings of fruit and at least one serving of vegetables daily and complying with a GFD. Different from the EC, the sDOR.2-6yTM scores did not differ between the participants complying with a GFD. The sDOR.2-6yTM mealtime structure domain scores were significantly associated with the EC eating attitude, food acceptance, contextual skills, and total. These findings support the need for greater attention to exploring the division of responsibility in feeding and EC in pediatric celiac disease, potentially enhancing intervention strategies for patients and their families.

Efficacy of a Low-FODMAP Diet for Coeliac Patients with Persistent IBS-like Symptoms despite a Gluten-Free Diet: A Systematic Review.

Background: Persistent symptoms in coeliac disease (CD) can be due to not only poor gluten-free diet (GFD) adherence and complications of CD, but also functional gastrointestinal disorders such as irritable bowel syndrome (IBS). Although the role of a low fermentable oligo-, di-, and monosaccharides and polyols (FODMAP) diet is well-established in IBS, little data are available on its role in coeliac patients with persistent IBS-like symptoms despite a GFD. Methods: We systematically reviewed the literature in accordance with the PRISMA guidelines for studies evaluating the role of FODMAPs and/or a low-FODMAP diet in coeliac patients with persistent symptoms. PubMed and Embase were searched from inception to 16 January 2024 for eligible full-text papers. The study protocol was registered on Open Science Framework. Results: A total of 239 records were identified, and six papers were included. Of these, four were interventional studies comparing a low-FODMAP GFD to a regular GFD for persistent symptoms in 115 total coeliac patients (two randomized controlled trials and two open-label studies). A low-FODMAP GFD for a minimum of 4 weeks was significantly more effective than a regular GFD in reducing symptoms (p < 0.05 in 3/4 studies). Dietary FODMAP content of a conventional GFD was significantly lower than that of non-coeliac patients on a gluten-containing diet (both p < 0.05), especially regarding high-FODMAP grain products. However, coeliac patients consumed more servings of fruits/vegetables high in FODMAP. No relationship between FODMAP intake and persistence of symptoms was reported. Conclusions: A low-FODMAP diet may be beneficial for uncomplicated celiac patients with persistent IBS-like symptoms despite strict adherence to a GFD.

Causal influence of celiac disease on the risk of sarcoidosis: A Mendelian randomization study.

Observational research shows a link between celiac disease (CeD) and sarcoidosis, but the causal link between CeD and sarcoidosis is still unknown. A two-sample Mendelian randomization (MR) study was conducted to ascertain the causal connection between the 2 disorders. In our two-sample MR analysis, we identified independent genetic variants associated with CeD using publicly accessible GWAS data from people of European ancestry. Summary data for sarcoidosis were obtained from the FinnGen Consortium, the UK-Biobank, and a large GWAS dataset. To assess the association between CeD and sarcoidosis, our MR analysis used inverse variance weighted (IVW) as the primary method, incorporating the MR-Egger, weighted median (WM), and MR-PRESSO (outliers test) as a complementary method. In order to ensure that the findings were reliable, several sensitivity analyses were performed. Our study indicated that CeD had a significant causal relationship with sarcoidosis (IVW odds ratio (OR) = 1.13, 95% confidence interval (CI): 1.07-1.20, P = 5.58E-05; WM OR = 1.12, 95% CI: 1.03-1.23, P = 1.03E-02; MR-Egger OR = 1.07, 95% CI: 0.96-1.19, P = 2.20E-01). Additionally, we obtain the same results in the duplicated datasets as well, which makes our results even more reliable. The results of this investigation did not reveal any evidence of horizontal pleiotropy or heterogeneity. Our MR analysis showed a causal effect between CeD and an elevated risk of sarcoidosis. Further study is still needed to confirm the findings and look into the processes underlying these relationships.

Diagnostic Delay of Celiac Disease in Childhood.

Importance: The extent and factors associated with risk of diagnostic delay in pediatric celiac disease (CD) are poorly understood. Objectives: To investigate the diagnostic delay of CD in childhood, and to assess factors associated with this delay. Design, Setting, and Participants: Multicenter, retrospective, cross-sectional study (2010-2019) of pediatric (aged 0-18 years) patients with CD from 13 pediatric tertiary referral centers in Italy. Data were analyzed from January to June 2023. Main Outcomes and Measures: The overall diagnostic delay (ie, the time lapse occurring from the first symptoms or clinical data indicative of CD and the definitive diagnosis), further split into preconsultation and postconsultation diagnostic delay, were described. Univariable and multivariable linear regression models for factors associated with diagnostic delay were fitted. Factors associated with extreme diagnostic delay (ie, 1.5 × 75th percentile) and misdiagnosis were assessed. Results: A total of 3171 patients with CD were included. The mean (SD) age was 6.2 (3.9) years; 2010 patients (63.4%) were female; and 10 patients (0.3%) were Asian, 41 (1.3%) were Northern African, and 3115 (98.3%) were White. The median (IQR) overall diagnostic delay was 5 (2-11) months, and preconsultation and postconsultation diagnostic delay were 2 (0-6) months and 1 (0-3) month, respectively. The median (IQR) extreme overall diagnostic delay (586 cases [18.5%]) was 11 (5-131) months, and the preconsultation and postconsultation delays were 6 (2-120) and 3 (1-131) months, respectively. Patients who had a first diagnosis when aged less than 3 years (650 patients [20.5%]) showed a shorter diagnostic delay, both overall (median [IQR], 4 [1-7] months for patients aged less than 3 years vs 5 [2-12] months for others) and postconsultation (median [IQR], 1 [0-2] month for patients aged less than 3 years vs 2 [0-4] months for others). A shorter delay was registered in male patients, both overall (median [IQR], 4 [1-10] months for male patients vs 5 [2-12] months for female patients) and preconsultation (median [IQR], 1 [0-6] month for male patients vs 2 [0-6] months for female patients). Family history of CD was associated with lower preconsultation delay (odds ratio [OR], 0.59; 95% CI, 0.47-0.74) and lower overall extreme diagnostic delay (OR, 0.75; 95% CI, 0.56-0.99). Neurological symptoms (78 patients [21.5%]; OR, 1.35; 95% CI, 1.03-1.78), gastroesophageal reflux (9 patients [28.1%]; OR, 1.87; 95% CI, 1.02-3.42), and failure to thrive (215 patients [22.6%]; OR, 1.62; 95% CI, 1.31-2.00) showed a more frequent extreme diagnostic delay. A previous misdiagnosis (124 patients [4.0%]) was more frequently associated with gastroesophageal reflux disease, diarrhea, bloating, abdominal pain, constipation, fatigue, osteopenia, and villous atrophy (Marsh 3 classification). Conclusions and Relevance: In this cross-sectional study of pediatric CD, the diagnostic delay was rather short. Some factors associated with risk for longer diagnostic delay and misdiagnosis emerged, and these should be addressed in future studies.

New and old criteria for diagnosing celiac disease: do they really differ? A retrospective observational study.

BACKGROUND: The aim of this study is to compare two groups of celiac patients: the first one, in which diagnosis was based on a "biopsy sparing" approach according to the 2012 ESPGHAN criteria, and the second one, based on the biopsy approach like the one of the 1991 Revised Criteria, in order to find relevant difference for sex, M/F ratio, age at diagnosis, clinical features at the onset, presence and prevalence of concomitant autoimmune disorders. METHODS: Our study involves 61 patients having the Celiac Disease (CD) onset from February 2013 to February 2020. The 32 patients who received diagnosis according "biopsy sparing" criteria were enrolled in group (1) The 29 patients who received diagnosis by duodenal biopsy were enrolled in group (2) Prevalence of comorbidities was analysed through chi-square test. RESULTS: In group 1 the prevalence of comorbidities such as Insulin-Dependent Diabetes Mellitus (IDDM) and thyroiditis was of 53%, while in group 2 it was only of 24%. Analysing the IDDM prevalence between the two groups we found a relevant difference. At the same time, the prevalence of thyroiditis was also significantly different. In group 1, male patients, in particular, would seem to have a higher incidence of CD related autoimmune disorders. CONCLUSIONS: An increased prevalence of IDDM, thyroiditis and juvenile idiopathic arthritis (JIA) in the first group would show that the "biopsy sparing" approach could expose patients to a greater length of disease activity that might be responsible for the onset of such comorbidities. Further studies should be carried out on more numerous samples of patients in order to confirm or not these data.

Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet.

BACKGROUND: The gluten-free diet (GFD) has limitations, and there is intense research in the development of adjuvant therapies. AIM: To examine the effects of orally administered Aspergillus niger prolyl endopeptidase protease (AN-PEP) on inadvertent gluten exposure and symptom prevention in adult celiac disease (CeD) patients following their usual GFD. METHODS: This was an exploratory, double-blind, randomized, placebo-controlled trial that enrolled CeD patients on a long-term GFD. After a 4-wk run-in period, patients were randomized to 4 wk of two AN-PEP capsules (GliadinX; AVI Research, LLC, United States) at each of three meals per day or placebo. Outcome endpoints were: (1) Average weekly stool gluten immunogenic peptides (GIP) between the run-in and end of treatments and between AN-PEP and placebo; (2) celiac symptom index (CSI); (3) CeD-specific serology; and (4) quality of life. Stool samples were collected for GIP testing by ELISA every Tuesday and Friday during run-ins and treatments. RESULTS: Forty patients were randomized for the intention-to-treat analysis, and three were excluded from the per-protocol assessment. Overall, 628/640 (98.1%) stool samples were collected. GIP was undetectable (< 0.08 µg/g) in 65.6% of samples, and no differences between treatment arms were detected. Only 0.5% of samples had GIP concentrations sufficiently high (> 0.32 µg/g) to potentially cause mucosal damage. Median GIP concentration in the AN-PEP arm was 44.7% lower than in the run-in period. One-third of patients exhibiting GIP > 0.08 µg/g during run-in had lower or undetectable GIP after AN-PEP treatment. Compared with the run- in period, the proportion of symptomatic patients (CSI > 38) in the AN-PEP arm was significantly lower (P < 0.03). AN-PEP did not result in changes in specific serologies. CONCLUSION: This exploratory study conducted in a real-life setting revealed high adherence to the GFD. The AN-PEP treatment did not significantly reduce the overall GIP stool concentration. However, given the observation of a significantly lower prevalence of patients with severe symptoms in the AN-PEP arm, further clinical research is warranted.

Microbiological quality of gluten-free meals, naturally gluten free foods, and gluten free-labelled products.

Background: The rising prevalence of gluten-related disorders such as celiac disease explains the increased consumption of gluten-free foods (GFF). However, these foods must be safe in terms of both gluten content and contamination by pathogenic microorganisms in order to avoid food poisoning. Objective: The objective of this study was to assess the microbiological quality of gluten-free meals, naturally gluten free foods, and gluten free-labelled products. Material and Methods: We collected 62 GFF samples including 20 meals (M-GF), 22 naturally gluten free (N-GFF) and 20 labelled (L-GFF) products, which were investigated for microbiological contamination according to Moroccan regulations guidelines, issued by the International Organization for Standardization (ISO). The analysis consisted of the detection of Salmonella and Listeria monocytogenes in each sample, and the quantification of the microbial load of the following six micro-organisms: total aerobic mesophilic flora, total coliforms, fecal coliforms, Staphylococcus aureus, Sulphite-Reducing Anaerobic, and yeasts and molds. Results: A total of 372 analyses were carried out, showing a microbiological contamination rate of 5.1%. This contamination concerned N-GFF in 8.3% (predominantly with yeasts and molds), and meals prepared at home in 11.7 (predominantly with Staphylococcus aureus and coliforms). Only one case (0.8%) of contamination was observed in products labelled gluten-free and no contamination was noticed in meals prepared in food services. Listeria monocytgenes and Salmonella were not detected in any samples of food analyzed. These results indicate a good compliance of L-GFP and M-GF prepared in food services, while unsatisfactory quality was observed in N-GFF and M-GF prepared at home. Conclusion: Therefore, rigorous hygienic practices and adequate corrective measures should be considered by celiac patients, especially regarding the N-GFF and M-GF prepared at home.

Prevalence of eating disorders in patients with celiac disease: a comparative study with healthy individuals.

INTRODUCTION: Celiac disease is a chronic immune-mediated disease, which is triggered and maintained by gluten in genetically susceptible individuals. Eating disorders are a persistent disturbance in eating-related behavior that results in altered food consumption or absorption and that significantly impairs physical health or psychosocial functioning. OBJECTIVE: This study aimed at evaluating the prevalence of eating disorders in Brazilian celiac patients. METHODS: This cross-sectional study was conducted as online survey including adult celiac patients who agreed to participate and a paired control health group. Questionnaires included questions about socioeconomic data and celiac disease diagnosis, and a validated questionnaire about eating disorders (Eating Attitudes Test-26. RESULTS: In total, 741 responses were studied, with 484 from the celiac group and 257 from the control group. No significant difference was observed between the number of individuals at risk of developing eating disorder (p=0.39). Both groups showed a high risk of developing eating disorders (34.2% in the celiac group and 37.7% in the control group). Furthermore, among patients with celiac disease, we found higher scores on the Eating Attitudes Test-26 in those with depression (p=0.0013), those with living difficulty due to the disease (p<0.0001), and those dissatisfied with their weight (p<0.0001). CONCLUSION: In the sample analyzed, no greater risk of eating disorders was identified in patients with celiac disease compared with the control group. However, in general, about one-third of the respondents in each group had scores associated with the risk of eating disorders. Among celiac patients, depression, difficulties living with celiac disease, and being unhappy with one's weight were associated with higher risk for eating disorder.

Trends in Faecal Zonulin Concentrations in Paediatric Patients with Celiac Disease at Baseline and on a Gluten-Free Diet: Exploring Correlations with Other Faecal Biomarkers.

Celiac disease (CeD) is an autoimmune condition triggered by gluten in genetically predisposed individuals, affecting all ages. Intestinal permeability (IP) is crucial in the pathogenesis of CeD and it is primarily governed by tight junctions (TJs) that uphold the intestinal barrier's integrity. The protein zonulin plays a critical role in modulating the permeability of TJs having emerged as a potential non-invasive biomarker to study IP. The importance of this study lies in providing evidence for the usefulness of a non-invasive tool in the study of IP both at baseline and in the follow-up of paediatric patients with CeD. In this single-centre prospective observational study, we explored the correlation between faecal zonulin levels and others faecal and serum biomarkers for monitoring IP in CeD within the paediatric population. We also aimed to establish reference values for faecal zonulin in the paediatric population. We found that faecal zonulin and calprotectin values are higher at the onset of CeD compared with the control population. Specifically, the zonulin levels were 347.5 ng/mL as opposed to 177.7 ng/mL in the control population (p = 0.001), while calprotectin levels were 29.8 µg/g stool compared to 13.9 µg/g stool (p = 0.029). As the duration without gluten consumption increased, a significant reduction in faecal zonulin levels was observed in patients with CeD (348.5 ng/mL vs. 157.1 ng/mL; p = 0.002), along with a decrease in the prevalence of patients with vitamin D insufficiency (88.9% vs. 77.8%). We conclude that faecal zonulin concentrations were higher in the patients with active CeD compared with healthy individuals or those following a gluten-free diet (GFD). The significant decrease in their values over the duration of the GFD suggests the potential use of zonulin as an additional tool in monitoring adherence to a GFD.

Preparation and Immunochemical Characterization of a Water-Soluble Gluten Peptide Fraction for Improving the Diagnosis of Celiac Disease.

The diagnosis of celiac disease (CD) is complex and requires a multi-step procedure (symptoms, serology, duodenal biopsy, effect of a gluten-free diet, and optional genetic). The aim of the study was to contribute to the improvement of CD diagnosis by preparing a water-soluble gluten peptide fraction (called Solgluten) and by selecting gluten-specific enzyme-linked immunosorbent assays (ELISA) for the detection of gluten immunogenic gluten peptides (GIPs) in urine and blood serum spiked with Solgluten. Food-grade Solgluten was prepared by the extraction of a peptic digest of vital gluten with water, centrifugation, and freeze-drying. The process was relatively easy, repeatable, and cheap. The content of gliadin-derived GIPs was 491 mg/g. Solgluten was used as antigenic material to compare two competitive ELISA kits (R7021 and K3012) and two sandwich ELISA kits (M2114 and R7041) in their quality regarding the quantitation of GIPs in urine and blood serum. The quality parameters were the reactivity, sensitivity, coefficients of variation and determination, and curve shape. The evaluation of the kits showed a number of discrepancies in individual quality parameters measured in urine and serum. Due to the lowest limit of quantitation and the highest coefficient of determination, M2114 may be the first choice, while R7021 appeared to be less suitable because of the high coefficients of variation and unfavorable curve progression. The results set the stage for improving CD diagnosis by supplementing conventional blood tests with oral provocation with Solgluten and subsequent ELISA measurement of GIPs that could support the no-biopsy approach and by better assessing the effect of a gluten-free diet by monitoring adherence to the diet by measuring GIPs in urine and blood.

Differences in Plasma 25-Hydroxyvitamin D Levels at Diagnosis of Celiac Disease and Type 1 Diabetes.

AIM: The aim of this work is to assess the vitamin D levels, evaluated as plasma 25-hydroxyvitamin D of children with a new diagnosis of celiac disease (CD), of children with a new onset of type 1 diabetes (T1D) and in children with CD at diagnosis of T1D (T1D&CD). METHODS: In this single-center observational study, we collected data for four groups of children and adolescents: T1D, CD, T1D&CD, and a control group (CG). The CG included schoolchildren who had negative results during a mass screening campaign for CD and were not diagnosed for T1D, according to RIDI Marche registry data, were considered for the purposes of this study. Plasma 25-hydroxyvitamin D, 25(OH)D2, and 25(OH)D3 were considered as the parameters for evaluating vitamin D nutritional status, and the date of measurement was recorded to analyze vitamin D level seasonality. Vitamin D nutritional status was categorized as follows: severe deficiency (<10 ng/mL), deficiency (<20 ng/mL), insufficiency (20-29 ng/mL), or sufficiency/adequacy (≥30 ng/mL). The Kruskal-Wallis test was used to compare the groups. The association of 25(OH)D levels with health conditions and seasonal differences of 25(OH)D levels was analyzed using a multiple linear regression model. RESULTS: The number of children enrolled for the present study was 393: 131 in the CG, 131 CD, 109 T1D, and 22 T1D&CD. Significantly lower levels of vitamin D were displayed for children with CD, T1D, or both the diseases. Interestingly, severe vitamin D deficiency was detected in no children with CD, 1.5% of children in the CG, in 24.4% with T1D, and 31.8% with T1D&CD (p < 0.001). As expected, the CG children vitamin D levels were significantly influenced by seasonality. Contrarily, no seasonal differences were reported in children with CD, T1D, and T1D&CD. Multiple regression analysis showed that children with T1D and T1D&CD had lower 25(OH)D levels of 9.9 ng/mL (95% CI: 5.4; 14.5) and 14.4 ng/mL (95% CI: 6.2-22.7) compared to CG children (p < 0.001). CONCLUSIONS: Our results showed low levels of vitamin D diagnosis of T1D, CD, and T1D&CD; however, severe deficiency was only reported in children with T1D and T1D&CD. More studies are needed to better understand the role of this deficiency in children newly diagnosed with CD and T1D.

Persistent Barriers of the Gluten-Free Basic Food Basket: Availability, Cost, and Nutritional Composition Assessment.

Gluten-related disorders are treated with a gluten-free diet. The "basic food basket" (BFB) consists of a list of basic foods consumed by low-income groups in society, including those lowest-cost versions within each food category. To evaluate the cost, availability, and nutritional quality of the BFB and gluten-free BFB (GF-BFB), foods were photographed, registering their cost, availability, and nutritional characteristics, in high quality and mid-range supermarkets, wholesalers, health shops, and corner shops, matching each regular BFB product with a gluten-free equivalent. Of the 1177 potential products, the selection of lowest-cost foods yielded 55 and 47 products (BFB and GF-BFB, respectively). Breads/cereals and drinks showed the highest differences (279% and 146%, respectively) while meats and sausages showed the lowest ones (18.6%). The GF-BFB cost represents 30.1% of the minimum wage, which covers the cost of 5.2 and 3.3 of the BFB and GF-BFB per month, respectively. Availability ranged between 22.7 and 42.4%. Lower availability was associated with poorer nutritional quality in the GF-BFB, which provides 5% less energy, 26% more fat, and 25% less protein than the BFB. Only 47% of gluten-free products declared their "gluten-free" condition. The results strongly suggest that the GF-BFB must be redesigned to be both gluten-free and nutritionally adequate.

Health-related quality of life among celiacs in Portugal: a comparison between general and specific questionnaires.

Objective: This study aimed to compare the 36-Item Short Form Survey Instrument version 2 (SF-36-v2) (generic) and Celiac Disease Questionnaire (CDQ) (specific) questionnaires used to evaluate the quality of life (QoL) in celiac Portuguese adult individuals. Methods: This cross-sectional study used non-probabilistic sampling based on Portuguese celiac patients who accessed the online survey in 2022. The online data collection used a self-reported instrument composed of three parts: (i) socioeconomic, health, and gluten-free diet (GFD) adherence questions; (ii) SF-36 v2 - Portuguese version (generic questionnaire) and (iii) Celiac Disease Questionnaire (CDQ) (specific questionnaire). Results: A total of 234 individuals who accessed the survey completed the questionnaire. Seven of the eight SF-36 domains positively correlated to the specific questionnaire CDQ. The "General Health" domain (domain 4) showed a negative correlation with the CDQ. Differences in content between the two instruments might be able to explain this finding since the CDQ explores issues regarding the specificities of celiac disease (CD) and the lifelong GFD burden. About half of the sample from this study displayed poor diet adherence, it is possible that the SF-36 could not reflect the impact of CD treatment - the complete elimination of gluten from the diet - on patients' health. Therefore, this issue should be carefully evaluated in future research. Conclusion: Specific validated questionnaires for CD individuals, such as the CDQ, contemplate social, economic, and clinical variables that permeate the patient's life context. Therefore, these instruments may be more suitable for evaluating QoL in this public. However, using a general questionnaire such as the SF-36 would be indicated for comparing QOL between celiac patients and the general population or even between CD and other disease individuals. In this case, we recommend assessing GFD compliance for control parallelly.

Monitoring coeliac disease in 2024, time to change practice?

PURPOSE OF REVIEW: Persistent villous atrophy is associated with morbidity in coeliac disease and most commonly due to ongoing gluten ingestion. Current methods for assessing gluten exposure and persisting villous atrophy include dietary questionnaires and repeat duodenal biopsy, which have limited accuracy or are invasive. This review discusses adjunctive and/or novel tests that could be used to overcome these challenges. RECENT FINDINGS: Small bowel capsule endoscopy is well tolerated and helps to evaluate for persisting villous atrophy and importantly, complications associated with coeliac disease. Testing for urinary and/or stool gluten immunogenic peptides may help identify recent gluten exposure, but further studies are still warranted to evaluate the accuracy and applicability of this approach. Measuring spikes in circulating Interleukin-2 following gluten challenge has shown promise for coeliac disease diagnosis, and thus may serve as a useful confirmatory test in those with persisting symptoms but provides no information on mucosal inflammation. No specific gut microbial signature has been identified in coeliac disease; however, studies have shown a reduced microbial diversity in active disease, which with future refinement may prove clinically useful. SUMMARY: There is no evidence to support alternative methods for assessing persisting villous atrophy in coeliac disease over performing an up-to-date duodenal biopsy. Monitoring for adherence to a gluten-free diet remains clinically challenging and should be a priority for future research.

Path Towards Biopsy-Free Diagnosis of Celiac Disease in Pediatric Patients.

BACKGROUND: Laboratory testing for celiac disease in pediatric patients integrates serology, genetic susceptibility and duodenal biopsy examination. The 2023 American College of Gastroenterology guidelines recommend a biopsy-free approach in pediatric patients utilizing tissue transglutaminase antibody titers >10 times upper limit of normal and subsequent endomysial antibody seropositivity as sufficient for diagnosis. The objective of this study is to assess the diagnostic accuracy of biopsy-free approach at our pediatric hospital. METHODS: We conducted a retrospective study involving pediatric patients who underwent biopsy for diagnostic confirmation of celiac disease between May 2019 and May 2023. For these patients, the tissue transglutaminase and endomysial antibody test results were retrieved and performance of biopsy-free approach was assessed using the duodenal histology as the gold standard for celiac disease diagnosis. RESULTS: Tissue transglutaminase antibody titers >10 times upper limit of normal alone demonstrated a positive predictive value of 99% for identifying celiac disease in children. Although endomysial antibody testing is underutilized at our center, its inclusion further improved the predictability to 100 %. CONCLUSION: Positive predictive value of tissue transglutaminase antibody titers >10 times upper limit of normal is sufficiently high for celiac disease diagnosis in children and may allow for deferral of duodenal biopsy at diagnosis.

Prevalence and Predictors of Celiac Disease in Children With Constipation.

OBJECTIVE: To determine the prevalence of celiac disease and its predictors in children with constipation. METHODS: A hospital-based cross-sectional comparative study was conducted between November, 2018 to April, 2020. Children aged 1-12 years were screened for the presence of constipation as per ROME IV criteria and designated as cases. Age and sex matched healthy children with normal bowel habits were enrolled as comparison group. Participants underwent a detailed history and examination, and were screened for celiac disease by estimating serum anti-tissue transglutaminase IgA antibody levels (tTG-IgA). Upper gastrointestinal endoscopy and duodenal biopsy were performed in all participants who tested positive on screening (serum tTG-IgA ≥ 20 U/mL). The prevalence of celiac disease and associated factors were compared between the two groups. RESULTS: A total of 460 children (230 in each group) with mean (SD) age 64.08 (37.12) months were enrolled. Twenty-one (4.6%) children screened positive for anti tTG antibodies, among these 15 (75%) children had biopsy features suggestive of celiac disease (Marsh grade III). Children with constipation had significantly higher prevalence of celiac disease (5.65% vs 0.87%, P = 0.004) compared to children without constipation. Wasting and stunting were significantly associated with celiac disease in constipated children (P < 0.001). CONCLUSION: Children with constipation and associated growth failure have a high prevalence of celiac disease.

Efficacy and safety of gut microbiota-based therapies in autoimmune and rheumatic diseases: a systematic review and meta-analysis of 80 randomized controlled trials.

BACKGROUND: Previous randomized controlled trials (RCTs) suggested that gut microbiota-based therapies may be effective in treating autoimmune diseases, but a systematic summary is lacking. METHODS: Pubmed, EMbase, Sinomed, and other databases were searched for RCTs related to the treatment of autoimmune diseases with probiotics from inception to June 2022. RevMan 5.4 software was used for meta-analysis after 2 investigators independently screened literature, extracted data, and assessed the risk of bias of included studies. RESULTS: A total of 80 RCTs and 14 types of autoimmune disease [celiac sprue, SLE, and lupus nephritis (LN), RA, juvenile idiopathic arthritis (JIA), spondyloarthritis, psoriasis, fibromyalgia syndrome, MS, systemic sclerosis, type 1 diabetes mellitus (T1DM), oral lichen planus (OLP), Crohn's disease, ulcerative colitis] were included. The results showed that gut microbiota-based therapies may improve the symptoms and/or inflammatory factor of celiac sprue, SLE and LN, JIA, psoriasis, PSS, MS, systemic sclerosis, Crohn's disease, and ulcerative colitis. However, gut microbiota-based therapies may not improve the symptoms and/or inflammatory factor of spondyloarthritis and RA. Gut microbiota-based therapies may relieve the pain of fibromyalgia syndrome, but the effect on fibromyalgia impact questionnaire score is not significant. Gut microbiota-based therapies may improve HbA1c in T1DM, but its effect on total insulin requirement does not seem to be significant. These RCTs showed that probiotics did not increase the incidence of adverse events. CONCLUSIONS: Gut microbiota-based therapies may improve several autoimmune diseases (celiac sprue, SLE and LN, JIA, psoriasis, fibromyalgia syndrome, PSS, MS, T1DM, Crohn's disease, and ulcerative colitis).