Review

Authors: Xingxing Wu, Lin Qian, Kexin Liu...

Coeliac disease (CD), also known as gluten sensitive enteropathy, is an autoimmune intestinal disease induced by gluten in genetically susceptible individuals. Gluten is a common ingredient in daily diet and is one of the main environmental factors to induce coeliac disease. Adhering to gluten free diet (GFD) is an effective method for treating CD. Microbiota plays an extremely important role in maintaining human health, and diet is the main factor to regulate the composition and function of gut microbiota. Recent studies have shown that gluten metabolism is closely related to gastrointestinal tract (GIT) microbiota. With the increasing prevalence of coeliac disease, there is a need for alternative treatments to GFD. In this review, biological medication of gluten, relationship between gluten and gut microflora, effect of GFD on GIT microflora, and effect of probiotics on CD were reviewed. By analysing the research progress on relationship between gluten and gastrointestinal microbiome in coeliac disease, this review tried to explore the prospective and potential mechanism of microecological agents in treating coeliac disease.

Topics: Celiac Disease; Diet, Gluten-Free; Gastrointestinal Microbiome; Glutens; Humans; Probiotics; Prospective Studies

PubMed: 34647492
DOI: 10.1080/07853890.2021.1990392

Authors: Abdulbaqi Al-Toma, Umberto Volta, Renata Auricchio...

This guideline presents recommendations for the management of coeliac disease (CD) and other gluten-related disorders both in adults and children. There has been a substantial increase in the prevalence of CD over the last 50 years and many patients remain undiagnosed. Diagnostic testing, including serology and biopsy, should be performed on a gluten-containing diet. The diagnosis of CD is based on a combination of clinical, serological and histopathological data. In a group of children the diagnosis may be made without biopsy if strict criteria are available. The treatment for CD is primarily a gluten-free diet (GFD), which requires significant patient education, motivation and follow-up. Slow-responsiveness occurs frequently, particularly in those diagnosed in adulthood. Persistent or recurring symptoms necessitate a review of the original diagnosis, exclude alternative diagnoses, confirm dietary adherence (dietary review and serology) and follow-up biopsy. In addition, evaluation to exclude complications of CD, such as refractory CD or lymphoma, should be performed. The guideline also deals with other gluten-related disorders, such as dermatitis herpetiformis, which is a cutaneous manifestation of CD characterized by granular IgA deposits in the dermal papillae. The skin lesions clear with gluten withdrawal. Also, less well-defined conditions such as non-coeliac gluten sensitivity (NCGS) and gluten-sensitive neurological manifestations, such as ataxia, have been addressed. Newer therapeutic modalities for CD are being studied in clinical trials but are not yet approved for use in practice.

Topics: Adult; Celiac Disease; Child; Dermatitis Herpetiformis; Diet, Gluten-Free; Dietary Supplements; Humans; Immunotherapy; Quality of Life

PubMed: 31210940
DOI: 10.1177/2050640619844125

Authors: M Ines Pinto-Sanchez, Jocelyn A Silvester, Benjamin Lebwohl...

Progress has been made in understanding coeliac disease, a relatively frequent and underappreciated immune-mediated condition that occurs in genetically predisposed individuals. However, several gaps remain in knowledge related to diagnosis and management. The gluten-free diet, currently the only available management, is not curative or universally effective (some adherent patients have ongoing duodenal injury). Unprecedented numbers of emerging therapies, including some with novel tolerogenic mechanisms, are currently being investigated in clinical trials. In March 2020, the Celiac Disease Foundation and the Society for the Study of Celiac Disease convened a consensus workshop to identify high-yield areas of research that should be prioritized. Workshop participants included leading experts in clinical practice, academia, government and pharmaceutical development, as well as representatives from patient support groups in North America. This Roadmap summarizes key advances in the field of coeliac disease and provides information on important discussions from the consensus approach to address gaps and opportunities related to the pathogenesis, diagnosis and management of coeliac disease. The morbidity of coeliac disease is often underestimated, which has led to an unmet need to improve the management of these patients. Expanded research funding is needed as coeliac disease is a potentially curable disease.

Topics: Animals; Biomedical Research; Celiac Disease; Diet, Gluten-Free; Humans; Mice; Research Support as Topic; Societies, Medical; United States

PubMed: 34526700
DOI: 10.1038/s41575-021-00511-8

Review

Authors: Pilvi Laurikka, Laura Kivelä, Kalle Kurppa...

BACKGROUND

The best-known symptoms of coeliac disease are related to the gastrointestinal tract, but the disease may also present with various systemic manifestations outside the intestine. Some of these consequences may remain permanent in undiagnosed individuals or if the diagnostic delay is prolonged. However, for many of the systemic manifestations, the scientific evidence remains scant and contradictory.

AIMS AND METHODS

We conducted a narrative review of the most thoroughly studied and clinically relevant systemic consequences of coeliac disease, especially those that could be prevented or alleviated by early diagnosis. The review is intended particularly for physicians encountering these patients in daily clinical practice.

RESULTS

The possible systemic consequences of coeliac disease extend to multiple organ systems, the best studied of which are related to skeletal, reproductive, cardiovascular and neurological systems. Furthermore, the disease is associated with an elevated risk of psychiatric comorbidities, non-Hodgkin lymphomas and intestinal adenocarcinoma.

CONCLUSIONS

The various systemic consequences of coeliac disease play a significant role in the overall health of patients. Early diagnosis and treatment with a gluten-free diet appear to be beneficial for most, but not all of these conditions. The possible negative metabolic and psychosocial effects of the diet should be acknowledged during follow-up.

Topics: Celiac Disease; Comorbidity; Delayed Diagnosis; Diet, Gluten-Free; Glutens; Humans; Immunotherapy

PubMed: 35815828
DOI: 10.1111/apt.16912

Authors: Jonas F Ludvigsson, Daniel A Leffler, Julio C Bai...

OBJECTIVE

The literature suggests a lack of consensus on the use of terms related to coeliac disease (CD) and gluten.

DESIGN

A multidisciplinary task force of 16 physicians from seven countries used the electronic database PubMed to review the literature for CD-related terms up to January 2011. Teams of physicians then suggested a definition for each term, followed by feedback of these definitions through a web survey on definitions, discussions during a meeting in Oslo and phone conferences. In addition to 'CD', the following descriptors of CD were evaluated (in alphabetical order): asymptomatic, atypical, classical, latent, non-classical, overt, paediatric classical, potential, refractory, silent, subclinical, symptomatic, typical, CD serology, CD autoimmunity, genetically at risk of CD, dermatitis herpetiformis, gluten, gluten ataxia, gluten intolerance, gluten sensitivity and gliadin-specific antibodies.

RESULTS

CD was defined as 'a chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals'. Classical CD was defined as 'CD presenting with signs and symptoms of malabsorption. Diarrhoea, steatorrhoea, weight loss or growth failure is required.' 'Gluten-related disorders' is the suggested umbrella term for all diseases triggered by gluten and the term gluten intolerance should not to be used. Other definitions are presented in the paper.

CONCLUSION

This paper presents the Oslo definitions for CD-related terms.

Topics: Asymptomatic Diseases; Celiac Disease; Dermatitis Herpetiformis; Diet, Gluten-Free; Genetic Markers; Glutens; Humans; Phenotype; Recurrence; Terminology as Topic

PubMed: 22345659
DOI: 10.1136/gutjnl-2011-301346

Review

Authors: Elena F Verdu, Heather J Galipeau, Bana Jabri...

Several studies point towards alteration in gut microbiota composition and function in coeliac disease, some of which can precede the onset of disease and/or persist when patients are on a gluten-free diet. Evidence also exists that the gut microbiota might promote or reduce coeliac-disease-associated immunopathology. However, additional studies are required in humans and in mice (using gnotobiotic technology) to determine cause-effect relationships and to identify agents for modulating the gut microbiota as a therapeutic or preventative approach for coeliac disease. In this Review, we summarize the current evidence for altered gut microbiota composition in coeliac disease and discuss how the interplay between host genetics, environmental factors and the intestinal microbiota might contribute to its pathogenesis. Moreover, we highlight the importance of utilizing animal models and long-term clinical studies to gain insight into the mechanisms through which host-microbial interactions can influence host responses to gluten.

Topics: Animals; Celiac Disease; Disease Models, Animal; Gastrointestinal Microbiome; Genetic Predisposition to Disease; Homeostasis; Humans

PubMed: 26055247
DOI: 10.1038/nrgastro.2015.90

Review

Authors: Margaret R Dunne, Greg Byrne, Fernando G Chirdo...

Coeliac disease is a common small bowel enteropathy arising in genetically predisposed individuals and caused by ingestion of gluten in the diet. Great advances have been made in understanding the role of the adaptive immune system in response to gluten peptides. Despite detailed knowledge of these adaptive immune mechanisms, the complete series of pathogenic events responsible for development of the tissue lesion remains less certain. This review contributes to the field by discussing additional mechanisms which may also contribute to pathogenesis. These include the production of cytokines such as interleukin-15 by intestinal epithelial cells and local antigen presenting cells as a pivotal event in the disease process. A subset of unconventional T cells called gamma/delta T cells are also persistently expanded in the coeliac disease (CD) small intestinal epithelium and recent analysis has shown that these cells contribute to pathogenic inflammation. Other unconventional T cell subsets may play a local immunoregulatory role and require further study. It has also been suggested that, in addition to activation of pathogenic T helper cells by gluten peptides, other peptides may directly interact with the intestinal mucosa, further contributing to the disease process. We also discuss how myofibroblasts, a major source of tissue transglutaminase and metalloproteases, may play a key role in intestinal tissue remodeling. Contribution of each of these factors to pathogenesis is discussed to enhance our view of this complex disorder and to contribute to a wider understanding of chronic immune-mediated disease.

Topics: Adaptive Immunity; Celiac Disease; Humans; Immunity, Innate

PubMed: 32733456
DOI: 10.3389/fimmu.2020.01374

Authors: Luca Elli, Beatrice Marinoni

For decades, gluten-free dieting (GFD) has been accepted as the only therapeutic approach to coeliac disease (CD) and, more recently, for non-coeliac gluten sensitivity (NCGS), a term to refer to the so-called gluten-related disorders (GRD) [...].

Topics: Celiac Disease; Diet, Gluten-Free; Humans

PubMed: 30862034
DOI: 10.3390/nu11030589

Review

Authors: Charlotte Näslund-Koch, Niels Højsager Bennike, Lone Skov...

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.

Topics: Humans; Diet, Reducing; Obesity; Diet; Vitamins; Psoriasis; Dietary Supplements; Celiac Disease

PubMed: 38018738
DOI: No ID Found

Authors: Shuai Yuan, Fangyuan Jiang, Jie Chen...

BACKGROUND

Coeliac disease (CeD) has been associated with a broad range of diseases in observational data; however, whether these associations are causal remains undetermined. We conducted a phenome-wide Mendelian randomization analysis (MR-PheWAS) to investigate the comorbidities of CeD.

METHODS

Single nucleotide polymorphisms (SNPs) associated with CeD at the genome-wide significance threshold and without linkage disequilibrium (R <0.001) were selected from a genome-wide association study including 12,041 CeD cases as the instrumental variables. We first constructed a polygenic risk score for CeD and estimated its associations with 1060 unique clinical outcomes in the UK Biobank study (N = 385,917). We then used two-sample MR analysis to replicate the identified associations using data from the FinnGen study (N = 377,277). We performed a secondary analysis using a genetic instrument without extended MHC gene SNPs.

FINDINGS

Genetic liability to CeD was associated with 68 clinical outcomes in the UK Biobank, and 38 of the associations were replicated in the FinnGen study. Genetic liability to CeD was associated with a higher risk of several autoimmune diseases (type 1 diabetes and its complications, Graves' disease, Sjögren syndrome, chronic hepatitis, systemic and cutaneous lupus erythematosus, and sarcoidosis), non-Hodgkin's lymphoma, and osteoporosis and a lower risk of prostate diseases. The associations for type 1 diabetes and non-Hodgkin's lymphoma attenuated when excluding SNPs in the MHC region, indicating shared genetic aetiology.

INTERPRETATION

This study uncovers multiple clinical outcomes associated with genetic liability to CeD, which suggests the necessity of comorbidity monitoring among this population.

FUNDING

This project was funded by Karolinska Institutet and the Swedish Research Council.

Topics: Male; Humans; Celiac Disease; Diabetes Mellitus, Type 1; Genome-Wide Association Study; Mendelian Randomization Analysis; Comorbidity; Lymphoma, Non-Hodgkin; Polymorphism, Single Nucleotide

PubMed: 38382313
DOI: 10.1016/j.ebiom.2024.105033