Potential therapeutic options for celiac Disease: An update on Current evidence from Gluten-Free diet to cell therapy.

Celiac disease (CD) is a chronic autoimmune enteropathy and multifactorial disease caused by inappropriate immune responses to gluten in the small intestine. Weight loss, anemia, osteoporosis, arthritis, and hepatitis are among the extraintestinal manifestations of active CD. Currently, a strict lifelong gluten-free diet (GFD) is the only safe, effective, and available treatment. Despite the social burden, high expenses, and challenges of following a GFD, 2 to 5 percent of patients do not demonstrate clinical or pathophysiological improvement. Therefore, we need novel and alternative therapeutic approaches for patients. Innovative approaches encompass a broad spectrum of strategies, including enzymatic degradation of gluten, inhibition of intestinal permeability, modulation of the immune response, inhibition of the transglutaminase 2 (TG2) enzyme, blocking antigen presentation by HLA-DQ2/8, and induction of tolerance. Hence, this review is focused on comprehensive therapeutic strategies ranging from dietary approaches to novel methods such as antigen-based immunotherapy, cell and gene therapy, and the usage of nanoparticles for CD treatment.

Celiac Disease: A Review from Genetic to Treatment.

Celiac disease (CD) is a complex disorder influenced by genetic and environmental factors. When people with a genetic predisposition to CD consume gluten, an inflammatory response is triggered in the small intestine, and this reaction can be alleviated by the elimination of gluten from the diet. The clinical manifestations of CD vary greatly from person to person and begin at a young age or in adulthood. Influence of genetic factors on CD development is evident in carriers of the DQ2 and/or DQ8 allele. HLA genotypes are associated with gut colonization by bacteria, particularly in individuals suffering from CD. In addition, beneficial gut microbes are crucial for the production of DPP-4, which plays a key role in immune function, as well as metabolic and intestinal health. Therefore, probiotics have been recommended as a complementary food supplement in CD.

[Chronic diarrhoea: when is it celiac disease and when not?] / Chronische Durchfälle: Wann ist es eine Zöliakie und wann nicht?

Patients who come to clinical consultation for chronic diarrhoea (i.e., diarrhoea lasting for more than four weeks) may suffer from a wide range of clinical conditions. The possible diagnoses range from a misunderstanding of what can be considered normal and what pathological in terms of daily bowel movements, to a severe malabsorption syndrome. Since the list of possible causes of chronic diarrhoea can be puzzling, the physician's approach needs to be systematic and structured in order to allow the correct diagnosis and treatment. This article proposes an algorithm for the diagnosis of chronic diarrhoea and discusses in detail the key clinical aspects of celiac disease, which is considered a paradigmatic disease as regards chronic malabsorptive diarrhoea.

Tolerance-inducing therapies in coeliac disease - mechanisms, progress and future directions.

Coeliac disease is an autoinflammatory condition caused by immune reactions to cereal gluten proteins. Currently, the only available treatment for the condition is a lifelong avoidance of gluten proteins in the diet. There is an unmet need for alternative therapies. Coeliac disease has a strong association with certain HLA-DQ allotypes (DQ2.5, DQ2.2 and DQ8), and these disease-associated HLA-DQ molecules present deamidated gluten peptides to gluten-specific CD4+ T cells. The gluten-specific CD4+ T cells are the drivers of the immune reactions leading to coeliac disease. Once established, the clonotypes of gluten-specific CD4+ T cells persist for decades, explaining why patients must adhere to a gluten-free diet for life. Given the key pathogenic role of gluten-specific CD4+ T cells, tolerance-inducing therapies that target these T cells are attractive for treatment of the disorder. Lessons learned from coeliac disease might provide clues for treatment of other HLA-associated diseases for which the disease-driving antigens are unknown. Thus, intensive efforts have been and are currently implemented to bring an effective tolerance-inducing therapy for coeliac disease. This Review discusses mechanisms of the various approaches taken, summarizing the progress made, and highlights future directions in this field.

Gluten-related Disorders From Bench to Bedside.

Celiac disease, non-celiac gluten sensitivity, and wheat allergy comprise 3 of the main conditions with wheat- and gluten-containing foods as the symptom trigger. Distinguishing between these entities can be daunting. In this review, we compare and contrast celiac disease, non-celiac gluten sensitivity, and wheat allergy to allow clinicians to determine which diagnosis fits their patient to facilitate high-quality management and longitudinal care.

The importance of diet in psoriasis.

The impact of diet on psoriasis is not well studied but it is of interest to many patients. A hypocaloric diet with corresponding weight loss can reduce psoriasis severity in overweight or obese patients and should be considered an important supplement to conventional therapy, as argued in this review. Gluten-free diet might improve severity of psoriasis in patients with coeliac disease or merely presence of coeliac-specific antibodies. Mediterranean diet might also be beneficial. Overall, studies do not support a beneficial effect of micronutrient supplements (i.e., vitamin D, selenium, vitamin B12) in patients with normal serum levels.

Celiac disease: mechanisms and emerging therapeutics.

Celiac disease (CeD) is a widespread, gluten-induced, autoimmune disorder that lacks any medicinal therapy. Towards the goal of developing non-dietary treatments for CeD, research has focused on elucidating its molecular and cellular etiology. A model of pathogenesis has emerged centered on interactions between three molecular families: specific class II MHC proteins on antigen-presenting cells (APCs), deamidated gluten-derived peptides, and T cell receptors (TCRs) on inflammatory CD4+ T cells. Growing evidence suggests that this pathogenic axis can be pharmacologically targeted to protect patients from some of the adverse effects of dietary gluten. Further studies have revealed the existence of additional host and environmental contributors to disease initiation and tissue damage. This review summarizes our current understanding of CeD pathogenesis and how it is being harnessed for therapeutic design and development.

Intestinal proteases.

PURPOSE OF REVIEW: Proteases constitute a group of enzymes that hydrolyze peptide bonds. Intestinal proteases are an integral part of gut homeostasis and digestion. This review discusses the broader classification of proteases, regulation of proteolytic activity (PA) in the intestinal tract, and how dysregulation of intestinal proteases contributes to the pathophysiology of conditions such as irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and celiac disease. We also discuss recent advancements in therapeutic modulation that directly or indirectly target intestinal proteases and can be utilized to treat these illnesses. RECENT FINDINGS: Host and microbiota derived proteases have been associated with symptoms in subsets of patients with IBS, IBD and celiac disease. Elevated PA mediates barrier dysfunction, visceral hypersensitivity as well as immune activation and inflammation. Recent mechanistic studies have revealed the nature of disease-associated proteases and mechanisms regulating their activity, particularly those driven by the microbiota. Advancements in activity-based probes have allowed novel ways of in vivo imaging of PA. Newer strategies targeting proteases include monoclonal antibodies, engineered microbiota as well as specific protease inhibitors. SUMMARY: Significant progresses made in the detection as well as regulation of PA is likely to provide therapeutic advancements for gastrointestinal diseases.

Old and New Adjunctive Therapies in Celiac Disease and Refractory Celiac Disease: A Review.

Celiac disease (CD) is a chronic enteropathy caused by the ingestion of gluten in a genetically susceptible individual. Currently, a gluten-free diet (GFD) is the only recommended treatment. However, unintentional gluten ingestion or a persistent villous atrophy with malabsorption (regardless of a strict GFD) as in the case of Refractory Celiac Disease (RCD) represents a major issue. In this review, we have analysed and discussed data from both randomized controlled trials and observational studies concerning adjunctive therapies as well as novel therapies for the treatment of CD and RCD. The literature search was carried out through Medline and Scopus. In total, 2268 articles have been identified and 49 were included in this review (36 studies resulting from the search strategy and 13 from other sources). Today, GFD remains the only effective treatment, although steroids, mesalamine, and more recently biological therapies have found space in the complex management of RCD. Currently, studies evaluating the effectiveness of novel therapies are still limited and preliminary results have been controversial.

Lack of Follow-Up for Celiac Disease During Childhood Not Associated With Poor Health Outcomes: A Regional Swedish Cohort Study.

OBJECTIVES: The objective of the study is to examine the association between the lack of follow-up for celiac disease (CD) during childhood and dietary adherence, disease remission, and health-related quality of life (HRQoL). METHODS: We invited 243 randomly selected children diagnosed with CD in 2013-2018 in Gothenburg, Sweden, and 162 consented to participate (67%). We retrieved information on clinical follow-up and current wellbeing using medical and laboratory records data, as well as validated questionnaires on symptoms of CD, dietary adherence, and HRQoL. We analyzed tissue-transglutaminase antibodies (tTGA) as a measure of disease remission. We defined lack of follow-up as no CD-related physician/dietician-led visit or measurement of tTGA over the past 24 months of study enrollment. RESULTS: The mean age at study enrolment was 12.7 (range 7.8-18.2) years. Out of 162 children with an average disease duration of 5.3 (range 2.3-8.8) years, 23 (14%) lacked follow-up. tTGA had normalized in 94% [95% confidence interval (CI) = 71%-100%] of children without follow-up versus 91% (95% CI: 85%-95%) of children with continued follow-up. Of children without follow-up, 65% (95% CI: 38%-86%) reported a dietary adherence score indicating very good adherence, versus 72% (95% CI: 63%-80%) of those with continued follow-up. Also, lack of follow-up was not significantly associated with growth, symptom scores, or HRQoL. CONCLUSIONS: In this regional cohort study of mostly older children and adolescents, lack of follow-up for CD was not significantly linked to dietary adherence, disease remission, or HRQoL. How these results hold in larger, unselected samples with longer follow-up, including transition to adult care, warrants further study.

Updates in the diagnosis and management of coeliac disease.

Coeliac disease is a common autoimmune disorder induced by ingesting gluten, the protein component of wheat, barley, and rye. It is estimated that one-in-hundred people worldwide have coeliac disease, of whom the majority remain undiagnosed. Coeliac disease is characterized by a wide range of gastrointestinal and extraintestinal symptoms but can also present asymptomatically. Diagnosing coeliac disease depends on the concordance of clinical, serological and histopathological data. However, the diagnosis can be challenging and frequently overlooked. Undiagnosed coeliac disease is associated with an increased risk of complications and detrimental effects on quality of life. Early diagnosis and treatment of coeliac disease are necessary to reduce the risk of long-term complications.

Celiac Disease: An Academy of Nutrition and Dietetics Evidence-Based Nutrition Practice Guideline.

Celiac disease is an autoimmune disorder in which the immune system of genetically susceptible individuals elicits a reaction to gluten causing small intestine damage. If left undiagnosed and untreated, the resulting nutrition malabsorption can lead to anemia, bone disease, growth faltering, or other consequences. The condition is lifelong and lacks a cure; the only treatment is lifelong adherence to a gluten-free diet (GFD). This diet is challenging to follow and adversely influences quality of life; however, it is essential to ensure intestinal recovery and prevent future negative health consequences. The Academy of Nutrition and Dietetics convened an expert panel complemented by a celiac disease patient advocate to evaluate evidence for six topics, including medical nutrition therapy; the GFD; oat consumption; micronutrients; pro-/prebiotics; and the low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols diet. This publication outlines the Academy of Nutrition and Dietetics Evidence Analysis Library methods used to complete the systematic review and guideline development, and summarizes the recommendations and supporting evidence. The guidelines affirm that all individuals with celiac disease should follow a GFD (1C, Imperative) that may include gluten-free oats in adults (2D, Conditional). Children should follow a nutritionally adequate GFD that supports healthy growth and development (Consensus, Imperative) and does not unnecessarily restrict gluten-free oats (Consensus, Conditional). The guidelines indicate nutritional care should include routine nutritional assessment (Consensus, Imperative) and medical nutrition therapy (Consensus, Imperative). At this time, the guidelines do not support a recommendation for the addition of the low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols diet (2C, Conditional); prebiotic or probiotic supplementation (2D, Conditional); or micronutrient supplementation (in the absence of nutritional deficiency) (Consensus, Conditional). The 2021 Celiac Disease Evidence-Based Nutrition Guideline will assist registered dietitian nutritionists in providing appropriate evidence-based medical nutrition therapy to support people with celiac disease in achieving and maintaining nutritional health and avoiding adverse celiac disease consequences throughout their lives.

Follow-Up of Celiac Disease in Adults: "When, What, Who, and Where".

For patients with celiac disease (CeD), a lifelong gluten-free diet is not a voluntary lifestyle choice-it is a necessity. The key end points in clinical follow-up are symptom resolution, the normalization of weight, prevention of overweight, seroconversion, and negation or minimization of increased long-term morbidity. For the latter, a surrogate endpoint is mucosal healing, which means the normalization of histology to Marsh 0-1. Ideally, celiac follow-up care includes a multidisciplinary approach, effective referral processes, improved access that leverages technological advances, and following guidelines with the identification of measurable quality indicators, ideally informed by evidence-based research. Face-to-face CeD care and telemedicine are considered the standards for this process, although published data are insufficient. Guidelines and statements on diagnosis are readily available. However, data are lacking on optimal clinic visit intervals and outcomes and quality indicators such as improvement of symptoms, function and quality of life, survival and disease control, and how to most effectively use healthcare resources. The results of future research should provide the basis for general recommendations for evidence-based standards of quality of care in CeD.

The emerging paradigm of Unconventional T cells as a novel therapeutic target for celiac disease.

Celiac disease (CD) is an organ-specific autoimmune disorder that occurs in genetically predisposed individuals when exposed to exogenous dietary gluten. This exposure to wheat gluten and related proteins from rye and barley triggers an immune response which leads to the development of enteropathy associated with symptoms of bloating, diarrhea, or malabsorption. The sole current treatment is to follow a gluten-free diet for the rest of one's life. Intestinal barriers are enriched with Unconventional T cells such as iNKT, MAIT, and γδ T cells, which lack or express only a limited range of rearranged antigen receptors. Unconventional T cells play a crucial role in regulating mucosal barrier function and microbial colonization. Unconventional T cell populations are widely represented in diseased conditions, where changes in disease activity related to iNKT and MAIT cell reduction, as well as γδ T cell expansion, are demonstrated. In this review, we discuss the role and potential employment of Unconventional T cells as a therapeutic target in the pathophysiology of celiac disease.

Transition of Care in Celiac Disease.

Celiac disease (CD) is a gluten related disorder which affects all age-groups and occurs in genetically susceptible population after introduction of gluten in diet. The worldwide prevalence of CD is ~1% and it is higher in certain "at-risk groups". The clinical features are variable, ranging from classical diarrhea to an asymptomatic state. Diagnosis requires serology and duodenal histology although a non-biopsy diagnosis is recommended by European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) for a select group of children. Treatment of CD is with a life-long strict gluten free diet (GFD) along with correction of nutritional deficiencies. Regular follow-up to assess compliance and efficacy of GFD is mandatory. Non-responsive CD needs evaluation by a specialist as it can be due to incorrect diagnosis, poor dietary compliance, coexisting conditions like small bowel bacterial overgrowth, pancreatic insufficiency etc. and lastly, refractory CD. Most patients diagnosed as CD in childhood receive no medical or dietary supervision after transition to adulthood and nearly a third are non-compliant to GFD. No requirement of medications, patient's perception of understanding GFD and absence of symptoms with intermittent non-compliance leads to neglect of care after transition. Poor dietary adherence leads to nutritional deficiencies, osteoporosis, fertility issues and risk of malignancy. It is mandatory that the patients know about CD, need of strict GFD, regular follow-up, disease complications, and are capable of communicating with the health-care personnel before transition. Formulating a phased transition care program with joint pediatric and adult clinics is required for a successful transition and improving the long-term outcome.

Identifying and validating the educational needs to develop a Celiac Self-Care System.

BACKGROUND: Celiac disease is a major public health problem in many countries, including Iran. Considering the disease's exponential spread throughout the world and its risk factors, identifying the educational priorities and minimum data required to control and treat the disease is of great significance. METHODS: The present study was conducted in two phases in 2022. In the first phase, a questionnaire was developed based on the information obtained from a review of the literature. Later, the questionnaire was administered to 12 pundits in the fields of nutrition (n = 5), internal medicine (n = 4), and gastroenterology (n = 3). As a result, the necessary and important educational content was determined for developing the Celiac Self-Care System. RESULTS: According to the experts' viewpoints, the educational needs of patients were classified into nine categories of demographic information, clinical information, long-term complications, comorbidity, tests, medications, dietary recommendations, general recommendations, technical capabilities as well as 105 subcategories. CONCLUSIONS: Due to the increased prevalence of Celiac disease and the lack of an established minimum set of data, determining the required educational information is of great importance at the national level. Such information could be useful in implementing educational health programs to raise the public level of awareness. In the field of education, such contents can be employed in planning new technology based on mobile phones (mobile health), preparing registries, and producing widely used content.