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.

Celiac disease and nonceliac enteropathies.

PURPOSE OF REVIEW: This review highlights recent research in the field of celiac disease. RECENT FINDINGS: Epidemiological studies continue to identify celiac disease-associated diseases such as inflammatory arthritis, irritable bowel syndrome, and cardiovascular disease. Recently published consensus guidelines provide recommendations for the long-term management and monitoring of patients with celiac disease. There are multiple pharmaceutical therapies for celiac disease under investigation, and recent phase I and phase II trials are reviewed here. Finally, a recent trial of patients with nonceliac gluten sensitivity demonstrates a significant nocebo effect in this condition. SUMMARY: Recent advances in celiac disease include the development of new clinical guidelines as well as promising new therapeutics. Continued high-quality research is needed to improve the outcomes of patients with celiac disease and nonceliac enteropathies.

[The importance of amaranth products in the diet of children with gluten intolerance].

The study of gluten intolerance is a modern area of medical science. With the advent of new diagnostic capabilities and data on the forms of the disease, wide opportunities have opened up in optimizing the timing and invasiveness reducing of intervention during diagnosis and further monitoring of the child's health. However, despite all efforts, the basic method of treating all forms of gluten intolerance remains strict adherence to a gluten-free diet (GFD). It is known that GFD itself, as well as low adherence to its observance can lead to nutritional disorders. Therefore, the expansion of the diet at the expense of foods with high nutritional value will greatly contribute to the optimization of diet therapy and compensation for food restrictions. The purpose of the review was to evaluate the possibility of using amaranth products in a GFD to fill the need for nutrients in children with gluten intolerance. Material and methods. The search for literature data was carried out using PubMed, eLIBRARY, scholar.google platforms mainly over the last 5 years, using the keywords: gluten intolerance, children, amaranth, gluten-free diet. Results. An analysis of modern literary sources has shown that amaranth is a product of choice in diet therapy when following a GFD, since it is a pseudo-grain crop. The article presents data confirming the high nutritional value of amaranth due to the protein component and the features of the lipid fraction. The features of the amino acid composition and squalene content in comparison with other plant crops are discussed. The article contains information on the preservation of the beneficial properties of amaranth in finished foods, in particular, the addition of amaranth flour instead of corn starch increases the protein content by 32% and fiber by 152% in gluten-free bread without affecting the taste. The advantages of the chemical composition of amaranth are shown in comparison with other pseudo-cereals. The research results prove the effectiveness of using amaranth products in GFD to eliminate deficiency states in patients, normalize physical development in children with gluten intolerance, and increase patient adherence to the diet. Conclusion. The composition of amaranth and the available studies on the effectiveness of amaranth products consumption convincingly prove the advisability of using it in nutrition, especially under dietary restrictions or increased need for nutrients in childhood.

Food Avoidance beyond the Gluten-Free Diet and the Association with Quality of Life and Eating Attitudes and Behaviors in Adults with Celiac Disease.

BACKGROUND: The only treatment for Celiac Disease (CeD), which affects about 1% of the population, is a gluten-free diet (GFD). Studies have indicated an association between the GFD, a diminished quality of life (QOL), and maladaptive eating patterns. This study aims to explore food avoidance behaviors in adults with CeD. METHODS: This cross-sectional study assessed 50 adults with biopsy-confirmed CeD who completed validated surveys evaluating demographics, psychological factors, QOL, eating pathology, and food avoidance. RESULTS: Overall CDQOL scores were good (mean: 62.7 out of 100). However, 58.0% of the participants self-elected to avoid one or more additional foods without diagnosed allergies or intolerances. Those avoiding one or more other foods had lower QOL scores (57.4 (23.2) vs. 70.2 (15.9)) compared to those only avoiding gluten (p = 0.034). The mean depression score (CESD) for the group avoiding foods beyond gluten was in the depressive range, unlike those avoiding only gluten (16.0 (4.9) vs. 13.6 (4.0), p = 0.078), with 77% of those avoiding more than gluten scoring above the CESD cut-off point of 15, indicating clinical depression. CONCLUSIONS: Over half of participants (58%) reported avoiding additional foods beyond the GFD, a behavior associated with decreased QOL and increased depression.

Influence of a structured, 1-year-long dietary intervention regarding body composition and cardiovascular risk (ARCTIC) in coeliac disease: a protocol of a multicentre randomised controlled trial.

INTRODUCTION: Coeliac disease (CD) affects 1% of the population worldwide. The only available evidence-based treatment is a strict gluten-free diet (GFD), which can readily lead to weight gain and unfavourable metabolic changes (eg, dyslipidaemia, fatty liver disease and insulin resistance) if followed without adequate dietary control. That can lead to increased cardiovascular risk (CV). We planned a randomised controlled trial to test the effect of a group-based, structured, 1-year, advanced dietary education, per the proposal of a Mediterranean diet vs standard of care, regarding the most relevant CV risk factors (eg, metabolic parameters and body composition) in CD patients. METHODS AND ANALYSIS: Randomisation will occur after the baseline dietary education and interview in a 1:1 allocation ratio. Outcomes include anthropometric parameters (body composition analysis including weight, Body Mass Index, fat mass, per cent body fat, skeletal muscle mass, visceral fat area and total body water) and CV risk-related metabolic parameters (eg, lipid profile, homocysteine, fasting glucose, haemoglobin A1c, Homeostatic Model Assessment Index, metabolic hormones, waist circumference, blood pressure, liver function tests, liver steatosis rate and diet composition). In this study, we aim to draw attention to a new aspect regarding managing CD: dietary education can lead to a better quality of the GFD, thereby reducing the risk of potential metabolic and CV complications. ETHICS AND DISSEMINATION: The study was approved by the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (27521-5/2022/EÜIG). Findings will be disseminated at research conferences and in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05530070.

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.

Psychiatric Difficulties in Children with Celiac Disease and the Relationship between Adherence to Treatment and Parental Attitudes.

Our knowledge of the factors related to parenting styles affecting adherence to diet in children with celiac diseases (CDs) and the association between psychiatric difficulties and diet compliance is largely based on limited data. Therefore, our work aims to examine primarily coexisting psychiatric difficulties in children with CD and raising attitudes of their parents and secondarily the relationship among adherence to treatment, psychiatric difficulties, and parental attitudes. Children aged 4-12 years (n = 42) who have been followed up with the diagnosis of CD in a Paediatric Gastroenterology Outpatient Clinic were compared with those of healthy controls (n = 31). One of the parents was asked to fill out the socio-demographic information form, Diet Compliance Form (only the patient group), "Parental Attitude Research Instrument" (PARI) and Strengths and Difficulties Questionnaire-parent form (SDQ). The scores from "emotional problems," "peer relationship problems," and "total difficulties" areas were statistically significantly higher in the disease group than healthy controls. The average score of SDQ subscales and none of the PARI subscales differed between dietary compliance +/- groups. Significant positive correlations were detected between disease duration and PARI-overprotection/extreme motherhood (r = .421, P = .017) and PARI-strict/hard discipline (r = .368, P = .038) subscales. Clarifying the factors related to parenting that may affect patients' adherence to a gluten-free diet will contribute positively to the course of the disease and the quality of life of patients and their families.

Dietary Adherence to Recommendations among a Cohort of Adults and Teens with Celiac Disease Maintaining a Gluten-Free Diet Compared to a Nationally Representative Sample: A Cross-Sectional Study.

Celiac disease (CeD) is a common autoimmune condition, with a prevalence of ~1%. Currently, a gluten-free diet (GFD) is the only treatment option. Due to fortification rules excluding gluten-free products in the United States of America (U.S.A.), understanding the nutritional adequacy of a GFD is important for promoting optimal health among those with CeD. Cross-sectional examination of multiple 24 h dietary recalls from a study sample of 50 adults and 30 teens with CeD was used to determine nutritional adequacy and excesses according to U.S.A. recommendations. The results were compared with those of 15,777 adults and 2296 teens from a nationally representative sample not reporting CeD, the National Health and Nutrition Examination Survey (NHANES) 2009-2014. Compared with NHANES, our study population was more at risk of low folate and carbohydrate (adults) consumption, and of excessive niacin and vitamin A (teens), as well as saturated and total fat consumption (adults). Overall, though, compared with NHANES, our study participants had similar nutrient concerns but fewer nutritional imbalances, with some notable exceptions. In addition to maintaining a GFD, individuals with CeD should be counseled to maintain a balanced diet and to pay attention to nutrient-dense foods. Special attention should be given to teens in providing dietary counseling to potentially mitigate the risk of future morbidity.

Evaluation and treatment of celiac disease in the central and south of Iraq.

OBJECTIVE: Aim: To estimate the differences between patients with celiac disease based on symptoms, diagnosis, treatment, and follow-up. PATIENTS AND METHODS: Materials and Methods: A retrospective cross-sectional study carried out between July 1, 2022 and April 2023, enrolling 200 patients from different provinces of central and south Iraq with Celia disease, whose diagnosis depended on a specialized physician according to WHO guidelines with long-term follow-up. Participants were following up for three to six months in private clinics. Survey was written in English, and the questionnaire form contains 13 fields divided into three sections. Diagnosis of Celia before and after treatment parameters: Tissue Transglutaminase Antibody, IgG, Serum (tTg-Ig G), and tTg-IgA levels the fourth part included a glutin-free diet and symptomatic treatment. RESULTS: Results: Females and ages below 20 were most affected. 176(88%) patients had detectable tTG levels; after 3 months, 72(36.0%) patients had an increase in their body weight but less than 5 kg, while 14(7.0%) of the patients showed an increase of more than 5 kg. But after 6 months, 73(36.5%) patients had an increase in their body weight less than 5 kg, while 45(22.5%) of patients showed an increase of more than 5 kg. CONCLUSION: Conclusions: Celiac patient profile in central Iraq is not different from that in other parts of the world, with typical patient being female and under 30 years of age. The study highlighted to a certain degree that a gluten-free diet can have a modest and promising positive impact on BMI in some patients.

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.

Cassava (Manihot esculenta) Brazilian cultivars have different chemical compositions, present prebiotic potential, and beneficial effects on the colonic microbiota of celiac individuals.

The purpose of this study was to investigate the potential prebiotic properties of cassava cultivars from Northeast [Doce mel and Ourinho (OUR)] and South [Baiana, and IPR-Upira (UPI)] of Brazil in in vitro fermentation systems. The cultivars were evaluated for their chemical composition, and, then, two cultivars were selected (OUR and UPI) and subjected to in vitro gastrointestinal digestion to assess the effects on probiotics Lacticaseibacillus casei, Lactobacillus acidophilus, and Bifidobacterium animalis growth, metabolic activity, and prebiotic activity scores. Finally, the impact of cassava cultivars on the fecal microbiota of celiac individuals was evaluated using the 16S rRNA gene. Cassava cultivars have variable amounts of fiber, resistant starch, fructooligosaccharides (FOS), organic acids, phenolic compounds, and sugars, with OUR and UPI cultivars standing out. OUR and UPI cultivars contributed to the increase in the proliferation rates of L. casei (0.04-0.19), L. acidophilus (0.34-0.27), and B. animalis (0.10-0.03), resulting in more significant effects than FOS, an established prebiotic compound. Also, the positive scores of prebiotic activities with probiotic strains indicate OUR and UPI's ability to stimulate beneficial bacteria while limiting enteric competitors selectively. In addition, OUR and UPI promoted increased relative abundance of Bifidobacteriaceae, Enterococcaceae, and Lactobacillaceae in the fecal microbiota of celiac individuals while decreased Lachnospirales, Bacteroidales, and Oscillospirales. The results show that cassava cultivars caused beneficial changes in the composition and metabolic activity of the human intestinal microbiota of celiacs. OUR and UPI cultivars from the Northeast and South of Brazil could be considered potential prebiotic ingredients for use in the formulation of functional foods and dietary supplements.

Clinical presentation and factors associated with gluten exposure in children with celiac disease.

OBJECTIVES: The prevalence of celiac disease (CeD) is increasing, yet it is still underdiagnosed, in part because of its heterogeneous presentation. Diagnostic criteria are evolving and management with strict adherence to a gluten-free diet is challenging for many. We aimed to characterize the clinical presentation of CeD among a large multicenter cohort of pediatric patients and to identify factors associated with gluten-free diet adherence. METHODS: Patients with CeD aged 0-18 years were recruited from 11 United States health centers. Parents completed surveys about gluten-free diet adherence and patient electronic health records were reviewed. Logistic regression analyses were performed to identify risk factors associated with gluten exposure. RESULTS: Charts were reviewed for 460 children with a median age of 6.4 years. Abdominal pain was reported in 57% of the cohort, but diverse symptoms were identified. Parent surveys were completed for 455 participants. Sixty-five (14%) participants were at high risk for gluten exposure based on parental reports of weekly or daily gluten exposure or eating gluten by choice in the past year. Participants under the age of 5 years had a lower risk of gluten exposure, while participants without repeat serology testing 18 months after initial diagnosis were at higher risk of gluten exposure. CONCLUSIONS: In a large, multicenter cohort of pediatric CeD patients, clinical presentation is highly variable, necessitating a high index of suspicion to make a diagnosis. Parent surveys indicate that 14% of patients are at high risk of gluten exposure, with patient age and lack of close follow-up associated with gluten-free diet adherence.

Iron deficiency without anemia in children with newly diagnosed celiac disease: 1-year follow-up of ferritin levels, with and without iron supplementation.

Iron deficiency (ID) without anemia is common in children with newly diagnosed celiac disease (CD). We aimed to assess the effect of iron supplementation versus no treatment on ferritin levels in newly diagnosed CD patients with ID adhering to a gluten-free diet (GFD). A retrospective review of children < 18 years, with low ferritin (≤ 10 ng/mL) and normal hemoglobin levels diagnosed between 12.2018 and 12.2021. We compared hemoglobin and ferritin levels between patients who received supplemental iron to those who did not. Data, including demographics, laboratory tests, and anthropometrics, were collected at baseline, and at 6 and 12 months following the initiation of the GFD. Adherence to GFD was assessed at each visit. Among 304 children diagnosed during the study period, 43 (14.1%) had iron deficiency anemia and 60 (19.7%) ID without anemia. Among children with ID, 29 (48%) were female, mean age 7.3 ± 3.9 years. Twenty-nine (48%) children received iron supplementation, and 31 (52%) did not. At the 12-month follow-up visit, tissue transglutaminase levels decreased significantly (p < 0.001), from a mean baseline level of 226.6 ± 47.8 to 34.5 ± 46 U/mL in children that received iron supplementation and from 234.2 ± 52.4 to 74.5 ± 88.7 U/mL in non-treated children, with no significant difference between the groups p = 0.22. Ferritin levels increased significantly (p < 0.001), from 9.0 ± 4.7 to 25.2 ± 20.8 ng/mL in patients who received supplementation and from 8.9 ± 3.8 to18.6 ± 9.5 ng/mL in patients who did not, with no significant difference between the groups (p = 0.46). CONCLUSION: Most children with newly diagnosed celiac disease and iron deficiency, who adhere to GFD, will normalize ferritin levels within 12 months without the need of iron supplementation. WHAT IS KNOWN: • Iron deficiency and iron deficiency anemia are common in newly diagnosed celiac disease. • Improved iron absorption may follow mucosal healing process in patients adhering to a strict gluten-free diet. WHAT IS NEW: • This single-center, retrospective cohort study evaluated the effect of iron supplementation versus no treatment on ferritin levels in children with newly diagnosed celiac disease with iron deficiency adhering to a gluten-free diet. • Most children with newly diagnosed celiac disease and iron deficiency, who adhere to gluten-free diet, will normalize ferritin levels within 12 months without the need of iron supplementation.

Bronchiectasis combined with chronic sinusitis following Celiac disease: a case report.

INTRODUCTION: Celiac disease is a disease triggered by a protein called gluten. Celiac disease has intestinal and extraintestinal manifestations. Bronchiectasis is a permanent dilation of the bronchi that causes symptoms, such as cough producing a large amount of sputum, recurrent respiratory infections, and breathlessness. In addition, bronchiectasis can present in 60% of cases with chronic rhinosinusitis. CASE PRESENTATION: A 40-year-old Arab woman presented with a worsening old cough with an increased amount of sputum; the patient was diagnosed with Celiac disease 7 months prior. Investigations started with laboratory tests followed by a computed tomography scan for the head and chest, bronchoscopy, bronchoalveolar lavage, and spirometry; the final diagnosis was bronchiectasis with chronic rhinosinusitis. She was advised to commit to the gluten-free diet, in addition to the medications prescribed for her bronchiectasis and chronic rhinosinusitis. CONCLUSION: Celiac disease and bronchiectasis might share an immunologic disturbance that caused both entities, so Celiac disease should be kept in mind as an etiology for pulmonary diseases.

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.

Quantitative proteomic analysis for characterization of protein components related to dough quality and celiac disease in wheat flour, dough, and heat-treated dough.

High-sensitivity 4D label-free proteomic technology was used to identify protein components related to gluten quality and celiac disease (CD) in strong-gluten wheat cultivar KX 3302 and medium-gluten wheat cultivar BN 207. The highly expressed storage protein components in KX3302 were high-molecular-weight-glutenin-subunits (HMW-GSs), α-gliadin, and globulin, whereas those in BN207 were γ-gliadin, low-molecular-weight-glutenin-subunits (LMW-GSs) and avenin-like proteins. In addition, BN207 had more upregulated metabolic proteins than KX3302. The abundance of storage proteins increased during dough formation. After heat treatment, the upregulated proteins accounted for 57.53 % of the total proteins, but the downregulated storage proteins accounted for 79.34 % of the total storage proteins. In cultivar KX3302, CD proteins mainly included α-gliadin and HMW-GSs, whereas in BN207, they were mainly γ-gliadin and LMW-GSs. Thermal treatment significantly reduces the expression levels of CD-related proteins. These findings provide a new perspective on reducing the content of CD-related proteins in wheat products.

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.