Advances in understanding and managing celiac disease: Pathophysiology and treatment strategies.

In this editorial, we comment on an article published in the recent issue of the World Journal of Gastroenterology. Celiac disease (CeD) is a disease occurring in genetically susceptible individuals, which is mainly characterized by gluten intolerance in the small intestine and clinical symptoms such as abdominal pain, diarrhea, and malnutrition. Therefore, patients often need a lifelong gluten-free diet, which greatly affects the quality of life and expenses of patients. The gold standard for diagnosis is intestinal mucosal biopsy, combined with serological and genetic tests. At present, the lack of safe, effective, and satisfactory drugs for CeD is mainly due to the complexity of its pathogenesis, and it is difficult to find a perfect target to solve the multi-level needs of patients. In this editorial, we mainly review the pathological mechanism of CeD and describe the current experimental and improved drugs for various pathological aspects.

Monitoring the Quality of Life and the Relationship between Quality of Life, Dietary Intervention, and Dietary Adherence in Patients with Coeliac Disease.

Inadequate adherence to a gluten-free diet in coeliac disease triggers autoimmune reactions and can reduce the quality of life. The strict diet requires constant vigilance, which can cause psychological distress. Our research aimed to assess the quality of life in adult patients with coeliac disease and to find a correlation between quality of life, dietary intervention, and adherence. The study included 51 adult patients with coeliac disease who completed a quality-of-life questionnaire. Adherence was assessed using serological tests and a dietary adherence test. The patients were divided into two groups: those on a gluten-free diet for at least three months (Group I) and newly diagnosed patients (Group II). Group I showed a significant decrease in the dysphoria subscale of the quality-of-life test between the first and last surveys. Poor quality of life was associated with worse adherence in Group II. A higher "Health concerns" quality of life subscale score was also associated with worse adherence in Group II. Our results suggest that dietetic care may be beneficial for patients with coeliac disease by reducing dysphoria. We recommend regular and long-term dietary monitoring from diagnosis to ensure adherence to a gluten-free diet and to maintain quality of life.

Impact of gluten-free diet (GFD) on some of cardiovascular risk factors: a systematic review and meta-analysis.

A gluten-free diet (GFD) may have a stronger potential impact on reducing cardiovascular (CV) risk factors, according to research evidence. We investigated the impact of GFD on CV risk variables by doing a systematic review and meta-analysis for this reason. We conducted a thorough database search starting on January 1, 2000, and ending on July 12, 2022. We used random-effects models to pool the data. Totally 19 articles met the eligible criteria and were included. Pooled findings indicated that intervention with GFD has a significantly beneficial effect on high-density lipoprotein (HDL) (WMD: 4.80 mg/dl, 95% CI: 2.09, 7.51, P = 0.001), systolic blood pressure (SBP) (WMD: -2.96 mmHg; 95% CI: -4.11, -1.81, P < 0.001), and C-reactive protein (CRP) (WMD: -0.40, mg/l, 95% CI: -0.67, -0.14, P = 0.002) levels. In celiac patients as well as with an intervention duration of more than 48 weeks, GFD increased TC and HDL compared to non-celiac patients and with an intervention duration lower than 48 weeks, respectively. The results of the present study showed that GFD can have a significant and beneficial effect on HDL, SBP, and CRP.

Social Adversities Associate with Worse Disease Control in Pediatric Celiac Disease.

OBJECTIVE: To characterize how social adversities influence disease control in children with celiac disease (CeD). STUDY DESIGN: We conducted a cross-sectional analysis of data from 325 eligible children ≤18 years old with CeD enrolled between 2015 through 2023 into iCureCeliac, a patient-centered US registry for CeD. We evaluated the associations between financial insecurity, social stigmatization, decreased health knowledge, and mental health comorbidity with 2 validated patient-reported outcomes on disease activity and gluten-free diet adherence: celiac symptom index and CeD adherence test, respectively. We used multivariable logistic and linear regression analysis to adjust for race, primary spoken language, and socioeconomic status. RESULTS: Among 325 children with available financial insecurity data, the median age was 11 years (IQR 8, 15), 67% were female, and 88% were White. In multivariable logistic regression, the odds of elevated disease activity among children with financial insecurity, social stigmatization, decreased health knowledge, and mental health comorbidity were 2.6 (95% CI 0.9, 8.0; P = .09), 2.8 (95% CI 1.6, 5.1; P < .001), 4.8 (95% CI 2.4, 9.8; P < .001), and 1.9 (95% CI 1.1, 3.3; P = .03), respectively. For insufficient dietary adherence, the respective odds were 1.6 (95% CI 0.5, 4.7; P = .43), 3.3 (95% CI 1.7, 6.5; P < .001), 2.9 (95% CI 1.5, 5.7; P = .002), and 2.3 (95% CI 1.2, 4.2; P = .01). Statistically significant associations in logistic regression aligned with results of linear models. CONCLUSIONS: Social stigmatization, decreased health knowledge, and mental health comorbidity were associated with worse disease control in pediatric CeD. Targeted interventions aimed at addressing these social adversities may improve disease activity and dietary adherence.

Growth Stunting and Nutritional Deficiencies among Children and Adolescents with Celiac Disease in Kuwait: A Case-Control Study.

BACKGROUND/OBJECTIVES: This study aimed to assess the nutritional status of children and adolescents with celiac disease (CD) in Kuwait and investigate the nutritional deficiencies and sociodemographic factors associated with growth stunting in this population. METHODS: This case-control study included 77 CD patients aged 3-18 years diagnosed with CD using IgA anti-tissue transglutaminase and duodenal biopsy and 33 healthy controls. Nutritional status was evaluated based on demographic and clinical characteristics, anthropometric measurements, and biochemical parameters. Univariate and multivariate logistic regression models were used to determine the association between CD and growth stunting. RESULTS: Approximately one-third (31%) of children with CD had stunted growth, 20.8% had a low body mass index for their age, and 5.2% had both growth stunting and wasting. Children with CD had higher odds of iron-deficiency anemia, vitamin D deficiency, anemia, and lower socioeconomic status. They were also younger and had decreased serum levels of vitamin D compared to the controls. These factors were all significantly associated with an increased risk of CD, collectively explaining over 50% of the risk. For growth stunting, lower education status among mothers, family income, and serum ferritin were identified as risk factors. CONCLUSIONS: A significant proportion of children and adolescents with CD had malnutrition, overt deficiencies, and impaired growth despite coherence with a gluten-free diet. RECOMMENDATION: Routine monitoring and targeted nutritional interventions are recommended for children and adolescents with CD to address malnutrition and growth stunting. Addressing socioeconomic disparities and enhancing maternal education may also help mitigate the risk factors.

Expression of MicroRNAs in Adults with Celiac Disease: A Narrative Review.

Celiac disease (CD) is an immune-mediated enteropathy triggered by the ingestion of proline- and glutamine-rich proteins, widely termed "gluten", in genetically susceptible individuals. CD induces an altered immune response that leads to chronic inflammation and duodenal mucosal damage. Currently, there are no specific tests for the accurate diagnosis of CD, and no drugs are available to treat this condition. The only available treatment strategy is lifelong adherence to a gluten-free diet. However, some studies have investigated the involvement of microRNAs (miRNAs) in CD pathogenesis. miRNAs are small noncoding ribonucleic acid molecules that regulate gene expression. Despite the growing number of studies on the role of miRNAs in autoimmune disorders, data on miRNAs and CD are scarce. Therefore, this study aimed to perform a literature review to summarize CD, miRNAs, and the potential interactions between miRNAs and CD in adults. This review shows that miRNA expression can suppress or stimulate pathways related to CD pathogenesis by regulating cell proliferation and differentiation, regulatory T-cell development, innate immune response, activation of the inflammatory cascade, focal adhesion, T-cell commitment, tissue transglutaminase synthesis, and cell cycle. Thus, identifying miRNAs and their related effects on CD could open new possibilities for diagnosis, prognosis, and follow-up of biomarkers.

Extra-digestive manifestations of celiac disease.

Introduction: Celiac disease (CD) is a chronic autoimmune disorder triggered by gluten ingestion in genetically predisposed individuals, presenting with a diverse range of symptoms that extend beyond the gastrointestinal tract. The condition's systemic nature is evidenced by its extra-digestive manifestations, which can affect various organs including the skin, joints, liver, and nervous system. Methods: This descriptive, retrospective study was conducted at a tertiary care center, focusing on adult patients diagnosed with CD who exhibited extra-digestive symptoms. Data were extracted from medical records of patients admitted between January 1, 2010 and June 30, 2024. Variables included demographic information, primary diagnosis, and associated extra-digestive manifestations. Descriptive statistical methods were employed for data analysis. Results: The sample included 108 patients with CD, the mean age was 43.21 years, with a predominance of females (76.85%). Iron deficiency anemia was the most common extra-digestive manifestation, affecting 20.37% of patients, followed by hypoproteinemia (18.52%) and Hashimoto's thyroiditis (14.81%). Co-occurrence analysis revealed frequent combinations of conditions, such as anemia with cardiovascular diseases and depressive disorders. Notable associations with neurological conditions like gluten ataxia and peripheral neuropathy were also observed. Conclusion: This study highlights the extensive extra-digestive manifestations of celiac disease, underscoring its systemic impact. The high prevalence of autoimmune conditions such as Hashimoto's thyroiditis and rheumatoid polyarthritis among CD patients reflects the need for holistic management strategies. Discrepancies between our findings and existing literature, particularly regarding skin and neurological conditions, emphasize the need for further research to better understand these associations and the long-term effects of a gluten-free diet.

The heart of celiac disease: understanding dilated cardiomyopathy, pathophysiology, and care-a systematic review.

BACKGROUND: Cardiac manifestations are infrequently reported in association with celiac disease, but clear link has not been established. The aim of this study was to explore the connection of dilated cardiomyopathy in celiac disease. This systematic review also provides a comprehensive overview of the association between celiac disease and various cardiac manifestations with pathophysiology and management. MAIN BODY: We searched PubMed, Cochrane Library, Google Scholar, Embase, Scopus, and Springer nature databases through June 4th 2023 for preferred studies related to our topic using MeSH and Regular keywords. After comprehensive search analysis, data extraction and quality appraisal 19 studies were included in the study. Although results varied across studies, majority of the studies revealed a positive link. Notably, some studies suggested an association between celiac disease and dilated cardiomyopathy, while others did not. These discrepancies could be attributed to differences in methodologies, study populations, and regional variations. Several studies have shown the association of various cardiac manifestations in celiac disease. CONCLUSION: Although dilated cardiomyopathy is associated with celiac disease in majority of the studies, there are also studies that conflict with the association. The complex relationship between celiac disease and cardiovascular manifestations potentiates the need for further research with standardized methodologies, larger sample sizes, and consideration of regional variations. Such insights are vital for improving clinical practice by establishing preventive strategies, active screening, early diagnosis, mitigating risks which helps in optimizing cardiovascular health in individuals with celiac disease.

Resilience in Adult Coeliac Patients on a Gluten-Free Diet: A Cross-Sectional Multicentre Italian Study.

BACKGROUND: Data on resilience, the ability to recover from adversity, in coeliac disease (CeD) are lacking. AIM: To assess the degree of resilience in patients with CeD on a gluten-free diet (GFD), and its association with clinical features, sociodemographic factors, psychological morbidity, and quality of life (QOL). METHODS: A cross-sectional multicentre Italian study was conducted on adult CeD patients between May 2022 and April 2023. Connor-Davidson Resilience Scale (CD-RISC), the Coeliac Disease-specific Quality of Life Scale (CD-QOL), the State-Trait Anxiety Inventory scale (STAI-Y), and the Beck Depression Inventory scale (BDI) were used to evaluate resilience, QOL, anxiety, and depression, respectively. A multivariate analysis was conducted to identify factors independently associated with the degree of resilience. RESULTS: A total of 305 patients (221 F, mean age at CeD diagnosis 36 ± 16 years) on a long-term GFD (median 8 years, IQR 3-17) were enrolled. A total of 298/305 patients (98%) had a high level of resilience (CD-RISC ≥ 35). At univariate analysis, resilience was statistically associated with male gender (p = 0.03), age at enrolment (p = 0.02), marital status (p = 0.03), QOL (p < 0.001), anxiety (p < 0.001), and depression (p < 0.001). On multivariate regression analysis, trait anxiety (STAI-Y2, p < 0.001) and depression (BDI, p = 0.02) were independent predictors of lower levels of resilience. CONCLUSIONS: Higher trait anxiety predicts lower levels of resilience. Targeted interventions in this subgroup of patients may be helpful for their management and follow-up.

Gastrointestinal and Hepatobiliary Manifestations Associated with Untreated Celiac Disease in Adults and Children: A Narrative Overview.

Celiac disease (CeD) is a chronic inflammatory disease of the small intestine, produced by ingesting dietary gluten products in susceptible people. Gluten causes an impairment of the mucosal surface and, consequently, an abnormal absorption of nutrients. Although malabsorption of essential nutrients is a major risk factor for various CeD-associated morbidities, genetic, immunological, and environmental factors also play an important role. The clinical presentation of CeD widely varies and can range from asymptomatic to full-blown symptoms due to the multi-system nature of CeD. The typical gastrointestinal (GI) manifestations of CeD include abdominal pain, diarrhea, bloating, and weight loss, but several hepatobiliary manifestations and a poor nutritional status have also been described. Currently, a gluten-free diet (GFD) is the only current evidence-based treatment that leads to the complete recovery of mucosal damage and the reversibility of its progression. Conversely, undiagnosed CeD might have severe consequences in children as well as in adult patients. This narrative overview aims to characterize the GI and hepatobiliary manifestations, nutritional deficiencies, and delayed pediatric development associated with unrecognized CeD in order to identify it promptly. Moreover, the role of GFD and how it could prevent long-term complications of CeD are described.

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.

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.

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.

Severe Liver Damage in an Obese Patient: Onset of Celiac Disease or Overlap Syndrome?

Celiac disease (CeD) is an enteropathy caused by the complex interaction between genetic, environmental, and individual immunological factors. Besides the hallmark of intestinal mucosal damage, CeD is a systemic disorder extending beyond the gastrointestinal tract and impacting various other organs, causing extraintestinal and atypical symptoms. The association between CeD and liver damage has been classified into three main categories: mild and asymptomatic liver injury, autoimmune liver injury, and liver failure. We present a case of severe liver damage with cirrhotic evolution in an obese 12-year-old boy who had been admitted due to generalized jaundice and localized abdominal pain in the right hypochondrium. In the course of investigating the etiology of severe liver disease, toxic, infectious, metabolic, obstructive, and genetic causes were excluded. Despite the patient's obesity, a diagnosis of CeD was established, and in accordance with autoimmune hepatitis (AIH) criteria, the patient was diagnosed with autoantibody-negative AIH associated to CeD.

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.

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.

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.

Impact of Gluten-Free and Casein-Free Diet on Behavioural Outcomes and Quality of Life of Autistic Children and Adolescents: A Scoping Review.

BACKGROUND: Gluten- and casein-containing foods could aggravate the symptoms of children and adolescents with autism spectrum disorder (ASD), and subsequently impact their quality of life. However, there is a mixed opinion among researchers concerning the impact of alternative diet on reducing ASD symptoms. OBJECTIVE: This scoping review aimed at examining the impact of the "gluten-free, casein-free" (GFCF) diet on health outcomes and the quality of life among autistic children and adolescents. METHODS: A scoping review of the literature was performed following the Joanna Briggs Institute (JBI) guidelines. Four databases, including EbscoHost, Medline, CINAHL, and ProQuest, were used to obtain subject-specific studies relevant to the research question and published between July 2013 and March 2024. A comprehensive search using keywords such as "autism spectrum disorder", "gluten-free diet", and "casein-free diet" was conducted to obtain articles related to the research focus area. Only full-text, peer-reviewed, written in English articles were selected. Data extraction and data analysis were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-extension to Scoping Review (PRISMA-ScR) protocol. RESULTS: From the initial 586 studies, a total of 27 articles were included in the final analysis of the review. The thematic analysis included "GFCF diet and improvement of the core autistic symptoms", "the gut-brain link", "dietary interventions and autism", "possible side effects due to the GCFC diet", and "inconclusive studies and mixed opinions". A majority of the studies showed a positive effect of the GFCF diet on a variety of autistic symptoms, including positive changes in cognitive skills, behaviour, and gastrointestinal symptoms, while some showed conflicting evidence. CONCLUSIONS: The currently available evidence on the impact of the "GFCF" diet on the quality of life of autistic children and adolescents may warrant potentially effective interventions for alleviating symptoms of autism spectrum disorders. However, this scoping review highlights the need for more research to provide more reliable evidence on the health outcomes and quality of life of ASD sufferers to guide practice.