The Effects of Gluten on Weight Gain, Hematological, Biochemical, and Various Endocrinological Parameters.

BACKGROUND/AIMS:  This study is aimed to compare the effects of nutrition which has been enriched with different amounts of gluten to gluten-free diets on weight gain, diabetogenic state, hematological, and biochemical parameters. MATERIALS AND METHODS:  A total of 40 newly weaned male Wistar albino rats used in the study were randomized into 4 different groups based on the gluten rations they were given. Following 12 weeks of diet they were killed and intracardiac blood samples were collected. Groups were identified as group 1 (n = 10): control group; normal rat ration containing wheat, group 2 (n = 10): gluten-free diet, group 3 (n = 10): ration containing medium level of gluten (normal rat diet+6% vital gluten) and group 4 (n = 10): ration containing high level of gluten (normal rat diet+12% vital gluten). RESULTS:  In groups 3 and 4, high-density lipoprotein was found to be higher than the other 2groups. However, when group 2 results were compared to the other groups; the highest T3, T4, creatinine and B12 levels and the lowest gluten-specific IgE level were observed. alanine aminotransferase and aspartate aminotransferase levels were found to be higher in group 1 compared to the other 3 groups. No statistically significant difference was detected between the groups in terms of other parameters. CONCLUSION:  This study provides evidence that a gluten-containing diet does not cause weight gain, has no diabetogenic effect, and also does not adversely affect general health in relation to hematological, biochemical, and various endocrinological parameters.

Gluten-Free Diet Adherence Tools for Individuals with Celiac Disease: A Systematic Review and Meta-Analysis of Tools Compared to Laboratory Tests.

This systematic review aimed to find the tool that best predicts celiac individuals' adherence to a gluten-free diet (GFD). The Transparent Reporting of Multivariable Prediction Models for Individual Prognosis or Diagnosis (TRIPOD-SRMA) guideline was used for the construction and collection of data from eight scientific databases (PubMed, EMBASE, LILACS, Web of Science, LIVIVO, SCOPUS, Google Scholar, and Proquest) on 16 November 2023. The inclusion criteria were studies involving individuals with celiac disease (CD) who were over 18 years old and on a GFD for at least six months, using a questionnaire to predict adherence to a GFD, and comparing it with laboratory tests (serological tests, gluten immunogenic peptide-GIP, or biopsy). Review articles, book chapters, and studies without sufficient data were excluded. The Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modeling Studies (CHARMS) was used for data collection from the selected primary studies, and their risk of bias and quality was assessed using the Prediction Risk of Bias Assessment Tool (PROBAST). The association between the GFD adherence determined by the tool and laboratory test was assessed using the phi contingency coefficient. The studies included in this review used four different tools to evaluate GFD adherence: BIAGI score, Coeliac Dietary Adherence Test (CDAT), self-report questions, and interviews. The comparison method most often used was biopsy (n = 19; 59.3%), followed by serology (n = 14; 43.7%) and gluten immunogenic peptides (GIPs) (n = 4; 12.5%). There were no significant differences between the interview, self-report, and BIAGI tools used to evaluate GFD adherence. These tools were better associated with GFD adherence than the CDAT. Considering their cost, application time, and prediction capacity, the self-report and BIAGI were the preferred tools for evaluating GFD adherence.

Importance of an Ongoing Nutritional Counselling Intervention on Eating Habits of Newly Diagnosed Children with Celiac Disease.

A strict lifelong gluten-free diet (GFD) is the current treatment for the management of celiac disease (CD). Several studies have demonstrated that without proper dietary assessment, this diet leads to nutritional deficiencies and/or imbalances. The present study aimed to improve the dietary habits of newly diagnosed children with CD through ongoing and face-to-face dietary counseling. Forty-three participants were followed during the first year after CD diagnosis. Dietary data were collected at diagnosis (Vt0), after 3 months on a GFD (Vt3), and after 1 year following a GFD (Vt12). Participants completed a 3-day 24-h food recall, a food frequency questionnaire, and the KIDMED index. After each data collection, participants received dietary assessment and nutritional education. Participants consumed more plant-origin foods after the intervention, with most of them reaching the daily recommendations. Fresh food intake increased and that of ultra-processed foods decreased. Compliance with the Mediterranean diet also improved. Personalized dietary assessment and ongoing follow-up improved the dietary patterns of children recently diagnosed with CD, highlighting the importance of dietitian involvement in the management of CD.

Compliance and Attitudes towards the Gluten-Free Diet in Celiac Patients in Italy: What Has Changed after a Decade?

This study aims were (i) to describe Italian celiac patients who agreed to participate in the latest web survey and their attitudes toward the GF diet (compliance, perceived limitations, and worries) and (ii) to compare the answers given by the 2011 and 2022 responders. The self-administered questionnaire was distributed through the Italian Coeliac Association channels (link on social media, websites, and newsletters) to all of the celiac patients willing to participate in 2011 and 2022 (2427 and 3529 responders who answered the same questions, respectively). Descriptive analyses and the Pearson's chi-squared test were performed. The responders were 1 to 84 years old and mainly female. The prevalence of adherent patients in 2022 was 91%, with the highest value (94%) in children (≤10 years old) and adolescents (15-17 years old). Overall, young adults were the most worried group. About a decade after the first survey, we observed a decreasing prevalence of transgression events (-5%) and (at least) occasional temptation (-17%), a decreasing prevalence of health-related and general worries, but an increasing prevalence of social life withdrawal. In conclusion, it is important to periodically monitor celiac patients' compliance and attitudes towards the gluten-free diet. As also highlighted in international guidelines, a reorganization of the diagnosis/follow-up visits, including an expert dietary consultation, is needed.

Knowledge Gaps in Gluten-Free Diet Awareness among Patients and Healthcare Professionals: A Call for Enhanced Nutritional Education.

Diet is the only treatment for celiac disease (CeD), and good adherence to a gluten-free diet (GFD) is the only way to ensure complete remission and to prevent complications. Limited education about the disease and a GFD is an attributing factor to inadequate adherence. Thus, our aim was to assess the current knowledge about a GFD and the clinical monitoring of adherence to the diet among CeD people and HCPs. Specific questionnaires were designed and distributed to assess the knowledge of CeD people (Q1 questionnaire) (n = 2437) and to analyze the follow-up of the disease from the perspective of patients (Q2 questionnaire) (n = 1294) and HCPs (Q3 questionnaire) (n = 346). Two-thirds of HCPs specialized in pediatric care, while one-third did so in adult care. In CeD people, general questions regarding food classification and cross-contamination are well understood. When patients have doubts, 51.4% reported using the Internet and social networks. Thus, it is crucial that resources like social media are reliable and provide valuable information. Q3 revealed the lack of time to follow up the diet after diagnosis (48% of HCPs allocate < 15 min), the interest in further training, and the need for a professional specialized in diets within the healthcare system. In conclusion, it is essential to enhance nutritional education to increase awareness of a GFD.

Digesting gluten with oral endopeptidases to improve the management of celiac disease.

In our editorial, we want to comment on the article by Stefanolo et al titled "Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet". Celiac disease is an immune-mediated disorder triggered by dietary gluten in genetically predisposed individuals. Although avoiding gluten can permit patients to live symptom-free, ongoing voluntary or involuntary exposure to gluten is common and associated with persistent villous atrophy in small bowel mucosa. As villous atrophy predisposes patients to life threatening complications, such as osteoporotic fractures or malignancies, therapeutic adjuncts to gluten-free diet become important to improve patients' quality of life and, if these adjuncts can be shown to improve villous atrophy, avoid complications. Oral administration of enzyme preparations, such as endopeptidases that digest gluten and mitigate its antigenicity to trigger inflammation, is one clinical strategy under investigation. The article is about the utility of one endopeptidase isolated from Aspergillus niger. We critique findings of this clinical trial and also summarize endopeptidase-based as well as other strategies and how they can complement gluten-free diet in the management of celiac disease.

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

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

γδ+ T-Cells Is a Useful Biomarker for the Differential Diagnosis between Celiac Disease and Non-Celiac Gluten Sensitivity in Patients under Gluten Free Diet.

BACKGROUND: The differential diagnosis between patients with celiac disease (CD) and non-celiac gluten sensitivity (NCGS) is difficult when a gluten-free diet (GFD) has been initiated before the diagnostic work-up. Isolated increases in TCRγδ+ and celiac lymphogram (increased TCRγδ+ plus decreased CD3-) may enable differential diagnosis in this challenging clinical setting. This study evaluated: (1) the accuracy of %TCRγδ+ and celiac lymphogram for diagnosing CD before and after GFD and for differentiation with NCGS; (2) TCRγδ+ kinetics at baseline and after starting GFD in both CD and NCGS. METHODS: The inclusion criteria were patients with CD (n = 104), NCGS (n = 37), and healthy volunteers (n = 18). An intestinal biopsy for intraepithelial lymphogram by flow cytometry was performed at baseline and after GFD. The optimal cutoff for CD diagnostic accuracy was established by maximizing the Youden index and via logistic regression. RESULTS: %TCRγδ+ showed better diagnostic accuracy than celiac lymphogram for identifying CD before and after GFD initiation. With a cutoff > 13.31, the accuracy for diagnosing CD in patients under GFD was 0.88 [0.80-0.93], whereas the accuracy for diagnosing NCGS (%TCRγδ+ ≤ 13.31) was 0.84 [0.76-0.89]. The percentage of TCRγδ+ cells showed differential kinetics between CD (baseline 22.7% [IQR, 16.4-33.6] vs. after GFD 26.4% [IQR, 17.8-36.8]; p = 0.026) and NCGS (baseline 9.4% [IQR, 4.1-14.6] vs. after GFD 6.4% [IQR, 3.2-11]; p = 0.022). CONCLUSION: TCRγδ+ T cell assessment accurately diagnoses CD before and after a GFD. Increased TCRγδ+ was maintained in the long term after GFD in CD but not in NCGS. Altogether, this suggests the potential usefulness of this marker for the differential diagnosis of these two entities in patients on a GFD.

Pigmented corn as a gluten-free source of polyphenols with anti-inflammatory and antioxidant properties in CaCo-2 cells.

A high number of varieties from corn (Zea mays L.) have been consumed for long time all over the world, however pigmented varieties are recently gaining renewed attention due to their beneficial effects and polyphenolic content. The natural lack of gluten makes corn suitable for consumption by celiac population, who need to control their inflammatory state through an appropriate gluten-free diet. The biological effects of polyphenols from pigmented corn are poorly investigated in the context of celiac disease. In this work, we analyzed through HPLC-DAD the phenolic composition of two Italian purple and red varieties ("Scagliolo Rosso" and "Rostrato di Rovetta", respectively) comparing their effects in human intestinal epithelial cells (CaCo-2 cells). The possible impact of gastro-intestinal digestion following oral consumption was assessed as well. The phenolic profile showed the presence of phenolic acids in both varieties, while anthocyanins were identified in Scagliolo Rosso only. After simulated digestion, the level of polyphenols did not significantly change and paralleled with an increased scavenging activity. In CaCo-2 cells, stimulated by a proinflammatory cocktail containing gliadin-derived peptides (IL-1ß, IFN-γ, digested gliadin), pigmented corn extracts inhibited the release of CXCL-10 and sICAM-1, with mechanisms partially ascribed to NF-κB impairment. At the same concentration (200 µg/mL), ROS production and catalase depletion were reverted through Nrf-2-independent mechanisms. Our data suggest that polyphenols from pigmented corns might help in controlling the inflammatory and oxidative state of people with celiac disease at intestinal level, at concentrations potentially achievable through a gluten-free diet.

Assessment of salivary microbiota profile as a potential diagnostic tool for pediatric celiac disease.

The association between oral dysbiosis and celiac disease (CD) remains poorly understood, as does the impact of CD-associated dysbiosis on disease development or exacerbation. This study aims to investigate alterations in salivary microbial composition among children with CD. In this cross-sectional study, saliva samples from 12 children with active CD (A-CD group), 14 children with CD on a gluten-free diet (GFD), and 10 healthy control (HC) children were analyzed using DNA sequencing targeting the 16S ribosomal RNA. Both patients in A-CD and GFD groups showed a significant increase (p = 0.0001) in the Bacteroidetes phylum, while the Actinobacteria phylum showed a significant decrease (p = 0.0001). Notably, the Rothia genus and R.aeria also demonstrated a significant decrease (p = 0.0001) within the both CD groups as compare to HC. Additionally, the control group displayed a significant increase (p = 0.006) in R.mucilaginosa species compared to both CD patient groups. Distinct bacterial strains were abundant in the saliva of patients with active CD, indicating a unique composition of the salivary microbiome in individuals with CD. These findings suggest that our approach to assessing salivary microbiota changes may contribute to developing noninvasive methods for diagnosing and treating CD.

Gluten Ataxia and mGluR1 Autoimmune Encephalitis Presenting as Acute Cerebellar Ataxia: A Case Report.

A Caucasian male in his 60s presented with acute onset of dizziness, dysarthria, and gait ataxia. Upon extensive workup, positive findings were cerebrospinal fluid (CSF) showing lymphocytic pleocytosis with oligoclonal bands, positive celiac disease autoantibodies in blood, a duodenal biopsy indicating lymphocytic infiltration, and positive anti-mGluR1 antibody titers in CSF. The patient was started on a strict gluten-free diet and intravenous immunoglobulin therapy for 5 days and showed mild consecutive improvements each day of treatment. He was discharged after 22 days, and was encouraged to continue gluten adherence, physical and speech therapy, and follow up with neuroimmunology. This report demonstrates that autoimmune encephalitis due to anti-mGluR1antibodies and gluten ataxia are both immune-mediated disorders that should be considered in acute cerebellar ataxia cases. By broadening the differential diagnosis and a comprehensive CSF analysis, identification of gluten ataxia and autoimmune encephalitis were beneficial in the management of this particular patient.

Nutritional, antioxidant and biological activity characterization of orange peel flour to produce nutraceutical gluten-free muffins.

Celiac disease - a prevalent food intolerance - requires strict adherence to a lifelong gluten-free (GF) diet as the only effective treatment. However, GF products often lack soluble fibre and have a high glycaemic index. Consequently, there is a pressing need in the food industry to develop GF products with improved nutritional profiles. In this context, the impact of incorporating orange peel flour (OPF) into muffins undergoing sourdough fermentation was examined, focusing on their technological, antioxidant, and nutritional characteristics. The functional properties of OPF were investigated using human colon carcinoma HCT8 cells as a model system. Treatment with OPF extract demonstrated a notable reduction in malignant cell viability and intracellular ROS levels, indicating potent antioxidant capabilities. Western blot analysis revealed significant alterations in key signalling pathways, including increased phosphorylation of NF-kB at serine 536 and reduced intracellular levels of caspase-3, alongside increased phosphorylation of RIPK3 and MLKL, suggesting potential involvement in necroptosis. OPF incorporation in muffins with sourdough increased antioxidant activity, reduced glycaemic index, and affected the volatile profile. Furthermore, based on simulated colonic fermentation, muffins with OPF showed a slight prebiotic effect, supported by the significant increase in bacillus-shaped lactic acid bacteria and Clostridia population. Overall, OPF-enriched muffins demonstrated considerable antioxidant effects and impacts on cell viability, underscoring their potential as functional ingredients in GF products. These findings signify the prospect of OPF enhancing the nutritional profiles and conferring health benefits of GF muffins.

Aspergillus niger prolyl endopeptidase in celiac disease.

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

Bone Health in Premenopausal Women with Coeliac Disease: An Observational Study.

Low bone mineral density (BMD) is common in adults with coeliac disease (CD), even in individuals adhering to a gluten-free diet (GFD). Women are more likely to have low BMD and have an increased risk of osteoporosis, so women with pre-existing low BMD related to CD are at an even higher risk. BMD assessed by dual X-ray absorptiometry (DXA) and bone quality assessed through quantitative ultrasound (QUS) were investigated in 31 premenopausal women with CD consuming a GFD, and 39 matched healthy controls from the Lower North Island, New Zealand. In addition, bone metabolism and nutrient status were assessed, and four-day diet diaries were used to estimate nutrient intake. No statistically significant differences were found in BMD assessed by DXA between the two groups at the hip, lumbar spine or forearm. However, the parameters measured by the QUS were significantly lower in CD participants. Dietary data indicated significantly lower intakes of energy, dietary fibre, magnesium and phosphorus in women with CD, likely as a result of a reduced intake of wholegrain foods, and suggested that both groups had inadequate intake of calcium. No significant differences were demonstrated in biochemical parameters. BMD and bone biomarkers indicated no differences between coeliac and healthy women in New Zealand. However, these findings suggest that QUS may be more sensitive for the coeliac population, due to the disease's affect on the trabecular bone, and warrant further research.

Adherence to the Gluten-Free Diet Role as a Mediating and Moderating of the Relationship between Food Insecurity and Health-Related Quality of Life in Adults with Celiac Disease: Cross-Sectional Study.

This cross-sectional study aimed to estimate the relationship between food insecurity (FI) and health-related quality of life (HRQoL) in patients with celiac disease (CD) and assess whether this relationship is mediated or moderated by adherence to the gluten-free diet (GFD). The results of 1162 samples of patients diagnosed with CD showed that 8.3% of individuals who have a combined score of less than 13 exhibited excellent or very good adherence to the GFD. Furthermore, moderate and fair to poor adherence to the GFD was demonstrated, respectively and 71.9% of the patients had poor HRQoL levels. A significant and moderate positive correlation between FI and GFD adherence (r = 0.489) was found, indicating that 24% of the variance in FI is shared with GFD adherence. The patients' gender, marital status, and monthly income made statistically significant contributions to the prediction (p < 0.05). Females had significantly lower HRQoL scores than males (B = -4.619, 95% CL: -6.08, -3.16) after holding all other variables constant. In conclusion, FI is mediated by GFD adherence to HRQoL. Moreover, a significant total effect relation was found between HRQoL and both FI and GFD adherence, suggesting that lowering symptoms and complications associated with CD may reduce the impact of FI on HRQoL.

Effects of Short-Term Gluten-Free Diet on Cardiovascular Biomarkers and Quality of Life in Healthy Individuals: A Prospective Interventional Study.

INTRODUCTION: The exposome concept includes nutrition as it significantly influences human health, impacting the onset and progression of diseases. Gluten-containing wheat products are an essential source of energy for the world's population. However, a rising number of non-celiac healthy individuals tend to reduce or completely avoid gluten-containing cereals for health reasons. AIM AND METHODS: This prospective interventional human study aimed to investigate whether short-term gluten avoidance improves cardiovascular endpoints and quality of life (QoL) in healthy volunteers. A cohort of 27 participants followed a strict gluten-free diet (GFD) for four weeks. Endothelial function measured by flow-mediated vasodilation (FMD), blood testing, plasma proteomics (Olink®) and QoL as measured by the World Health Organisation Quality-of-Life (WHOQOL) survey were investigated. RESULTS: GFD resulted in decreased leucocyte count and C-reactive protein levels along with a trend of reduced inflammation biomarkers determined by plasma proteomics. A positive trend indicated improvement in FMD, whereas other cardiovascular endpoints remained unchanged. In addition, no improvement in QoL was observed. CONCLUSION: In healthy individuals, a short-term GFD demonstrated anti-inflammatory effects but did not result in overall cardiovascular improvement or enhanced quality of life.

Associations between special diet and incidence risk of osteoporosis: a Mendelian randomization study.

Introduction: Osteoporosis is a prevalent challenge in clinical orthopedics, affecting a significant percentage of individuals aged 50 and above. The goal of this study was to comprehensively understand the relationships between a specialized dietary regimen and the risk of developing osteoporosis. Methods: This study employed extensive genome-wide association study (GWAS) summary statistics derived from the UK Biobank. It encompassed 8 kinds of special diets and 7 datasets pertaining to osteoporosis and associated symptoms. The principal analytical approach employed was the inverse-variance weighted method. Additionally, sensitivity analysis was employed to elucidate the diverse multiplicity patterns observed in the final model. Results: Our results showed that there is significant evidence that a gluten-free diet is associated with osteoporosis [odds ratio (OR): 1.080, 95% confidence interval (CI): 1.048-1.112, p = 4.23E-07)]. Furthermore, there exists a suggestive link between the three distinct dietary approaches and osteoporosis [(OR: 0.949, 95%CI: 0.929-0.970, p = 3.00E-06) for comprehensive consumption; (OR: 1.053, 95%CI: 1.018-1.089, p = 2.23E-03) for abstaining from wheat consumption; (OR: 1.036, 95%CI: 1.005-1.068, p = 1.97E-02) for abstaining from sugar consumption]. No additional correlation between the special dietary regimens and osteoporosis has been observed. Conclusion: Our research has uncovered a notable correlation between a gluten-free diet and the occurrence of osteoporosis. Furthermore, it exerts a promoting influence on the onset of osteoporosis, which stands in direct contradiction to the therapeutic principles for Celiac Disease's complications. As such, a novel association among these three elements is postulated.

The Usefulness of Intraepithelial Lymphocyte Immunophenotype Testing for the Diagnosis of Coeliac Disease in Clinical Practice.

BACKGROUND: The diagnosis of coeliac disease (CD) in adults is based on clinical, serological and histological criteria. The inappropriate performance of intestinal biopsies, non-specificity of mild histological lesions and initiation of a gluten-free diet (GFD) before biopsy may hamper the diagnosis. In these situations, determining the intraepithelial lymphogram of the duodenum by flow cytometry (IEL-FC) can be helpful. OBJECTIVES: To describe the clinical scenarios in which the IEL-FC is used and its impact on the diagnosis of CD. METHODS: All adult patients with suspected CD at three tertiary centres for whom the duodenal histology and IEL-FC were available were identified. Catassi and Fasano's diagnostic criteria and changes to a CD diagnosis after the IEL-FCs were collected. RESULTS: A total of 348 patients were included. The following indications for an IEL-FC formed part of the initial study for CD (38%): negative conventional work-up (32%), already on a GFD before duodenal biopsies (29%) and refractoriness to a GFD (2%). The IEL-FC facilitated a definitive diagnosis in 93% of patients with an uncertain diagnosis who had had a conventional work-up for CD or who were on a GFD before histology. CONCLUSIONS: The IEL-FC facilitates the confirmation or rejection of a diagnosis of CD in clinical scenarios in which a conventional work-up may be insufficient.

Potential Celiac Disease in Children: Health Status on A Long-Term Gluten-Containing Diet.

Potential celiac disease (PCD) is a clinical condition characterised by the presence of a positive CD-specific serology and a normal intestinal architecture. Asymptomatic PCD patients are generally advised to continue on a gluten-containing diet (GCD), but long-term risks of this approach have never been explored. In the present study, we aimed to investigate nutritional and autoimmune complications possibly developing overtime in a cohort of asymptomatic PCD children on a GCD. We compared children's parameters of growth, nutritional status, and autoimmunity between the time of diagnosis and on the occasion of their last medical check, after a long-term gluten-containing diet. Altogether, we collected data from 171 PCD children with a mean follow-up time of 3 years (range 0.35-15.3 years). During follow-up, although patients did not reduce their amount of daily gluten intake, their anti-tissue transglutaminase (anti-TG2) antibodies spontaneously and significantly decreased. Most parameters analysed had not changed during follow-up (height centile, ferritin, albumin, cholesterol, calcium, alkaline phosphatase, parathormone, and vitamin D) or even improved significantly (weight and BMI centile, haemoglobin, blood iron, HDL, glycaemia, and HbA1C, p < 0.05), always remaining within the limit of normality. Equally, autoantibodies for other concomitant autoimmune disorders did not increase overtime. Similar results were obtained excluding from analysis patients who had stopped producing anti-TG2 and those with a follow-up time < 3 years. Our pilot study has provided reassuring results regarding the maintenance of a gluten-containing diet in asymptomatic PCD children, even when long-term follow-up was considered.

Evaluation of Hearing Functions in Children with Celiac Disease and the Effect of Gluten-free Diet on these Functions.

OBJECTIVE: The present study aims to investigate the potential impact of celiac disease (CD) on hearing functions and assess the effect of a gluten-free diet (GFD) on this condition. MATERIALS AND METHODS: The study included 55 children with CD (110 ears) and 25 healthy controls (50 ears) matched for age and gender. The CD group was divided into adherent (n = 31) and nonadherent (n = 24) to GFD. Participants underwent tympanometry and pure tone audiometry assessments covering frequencies from 500 to 4000 Hz. RESULTS: Patients with CD showed significantly higher air and bone conduction hearing averages compared to the control group at frequencies of 500, 1000, 2000, and 4000 Hz for air conduction, and at 500 Hz for bone conduction (P < 0.05). Celiac patients, those who fully adhered to GFD, had notably higher air conduction hearing averages at 500, 2000, and 4000 Hz compared to healthy controls (P < 0.05). However, there was no difference in bone conduction hearing averages between the two groups. In contrast, celiac patients who did not comply with GFD had statistically significantly higher air and bone conduction hearing averages than the control group (P < 0.05), at frequencies of 500, 1000, and 4000 Hz for air conduction, and at 500 and 1000 Hz for bone conduction (P < 0.05). CONCLUSIONS: The study suggests that nonadherence to GFD may elevate the risk of hearing loss in children with CD. As a result, it is recommended to conduct hearing screenings for children with CD and underscore the importance of complying with GFD to mitigate further detrimental effects on hearing functions.