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Celiac Disease and Nonceliac Gluten Sensitivity: Update of the Pathophysiology, Diagnosis and Treatment

A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Clinical Nutrition".

Deadline for manuscript submissions: closed (15 April 2020) | Viewed by 21144

Special Issue Editors

Prof. Dr. Antonio Gasbarrini

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Guest Editor
1. Department of Translational Medicine and Surgery, School of Medicine, Catholic University, 00168 Rome, Italy
2. Center for Diagnosis and Treatment of Digestive Diseases, CEMAD, Gastroenterology Department, Fondazione Policlinico Gemelli, IRCCS, 00168 Rome, Italy
Interests: gastroenterology; oncology; digestive cancer; diverticular disease; cancer prevention; inflammatory bowel diseases; microbial communities; bioinformatics and computational biology
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Giovanni Cammarota

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Guest Editor
A. Gemelli” Hospital, Catholic University of the Sacred Heart; Gastroenterological Area; Rome, Italy
2. CEMAD-Centro Malattie Apparato Digerente, Digestive Diseases Center; Universita’ Cattolica del Sacro Cuore, Fondazione Policlinico Universitario Gemelli IRCCS, Roma, Italy
Interests: gastro-esophageal reflux; celiac disease; gastrointestinal endoscopy; gut microbiota; fecal microbiota transplantation

Special Issue Information

Dear Colleagues,

The avoidance of wheat- and gluten-containing products is a worldwide phenomenon, because the prevalence of gluten-related disorders is rising, and increasing numbers of individuals are empirically trying a gluten-free diet for a variety of signs and symptoms. Celiac disease (CD) is a common immune-mediated enteropathy characterized by gluten-induced small intestinal damage with loss of absorptive villi in genetically susceptible individuals. On the other hand, nonceliac gluten sensitivity (also referred to as wheat intolerance syndrome) is diagnosed in individuals who do not have celiac disease or wheat allergy but who have symptoms related to ingestion of gluten-containing grains, with symptomatic improvement on their withdrawal. However, while celiac disease is well-established, much remains unknown about how and whether gluten can be a trigger of gastrointestinal and/or extra-intestinal symptoms in patients without celiac disease. In addition, many questions remain unanswered, and although both conditions are treated with a gluten-free diet, distinguishing between celiac disease and nonceliac gluten sensitivity is important for long-term therapy.

The list of topics to be covered should deal with this exciting and evolving field, covering updated information concerning pathogenesis, role of the gut microbiota, evolving clinical presentations, diagnostic approaches, and new treatments appearing on the horizon.

Prof. Dr. Antonio Gasbarrini
Prof. Dr. Giovanni Cammarota
Guest Editors

Manuscript Submission Information

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Keywords

  • Celiac disease
  • Diagnosis
  • Diet
  • Nonceliac gluten sensitivity
  • Pathogenesis
  • Treatment
  • Wheat intolerance syndrome

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Published Papers (5 papers)

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Research

10 pages, 942 KiB  
Article
A Two-Sample Mendelian Randomization Analysis Investigates Associations Between Gut Microbiota and Celiac Disease
by Iraia García-Santisteban, Ariadna Cilleros-Portet, Elisabet Moyua-Ormazabal, Alexander Kurilshikov, Alexandra Zhernakova, Koldo Garcia-Etxebarria, Nora Fernandez-Jimenez and Jose Ramon Bilbao
Nutrients 2020, 12(5), 1420; https://doi.org/10.3390/nu12051420 - 14 May 2020
Cited by 27 | Viewed by 8059
Abstract
Celiac disease (CeD) is a complex immune-mediated inflammatory condition triggered by the ingestion of gluten in genetically predisposed individuals. Literature suggests that alterations in gut microbiota composition and function precede the onset of CeD. Considering that microbiota is partly determined by host genetics, [...] Read more.
Celiac disease (CeD) is a complex immune-mediated inflammatory condition triggered by the ingestion of gluten in genetically predisposed individuals. Literature suggests that alterations in gut microbiota composition and function precede the onset of CeD. Considering that microbiota is partly determined by host genetics, we speculated that the genetic makeup of CeD patients could elicit disease development through alterations in the intestinal microbiota. To evaluate potential causal relationships between gut microbiota and CeD, we performed a two-sample Mendelian randomization analysis (2SMR). Exposure data were obtained from the raw results of a previous genome-wide association study (GWAS) of gut microbiota and outcome data from summary statistics of CeD GWAS and Immunochip studies. We identified a number of putative associations between gut microbiota single nucleotide polymorphisms (SNPs) associated with CeD. Regarding bacterial composition, most of the associated SNPs were related to Firmicutes phylum, whose relative abundance has been previously reported to be altered in CeD patients. In terms of functional units, we linked a number of SNPs to several bacterial metabolic pathways that seemed to be related to CeD. Overall, this study represented the first 2SMR approach to elucidate the relationship between microbiome and CeD. Full article
(This article belongs to the Special Issue Celiac Disease and Nonceliac Gluten Sensitivity: Update of the Pathophysiology, Diagnosis and Treatment)
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10 pages, 239 KiB  
Article
The Long-Term Safety and Quality of Life Effects of Oats in Dermatitis Herpetiformis
by Anna Alakoski, Kaisa Hervonen, Eriika Mansikka, Timo Reunala, Katri Kaukinen, Laura Kivelä, Pilvi Laurikka, Heini Huhtala, Kalle Kurppa and Teea Salmi
Nutrients 2020, 12(4), 1060; https://doi.org/10.3390/nu12041060 - 11 Apr 2020
Cited by 9 | Viewed by 3053
Abstract
The treatment of choice for dermatitis herpetiformis (DH), a cutaneous manifestation of coeliac disease, is a life-long gluten-free diet (GFD). In a GFD, wheat, rye and barley should be strictly avoided, but the role of oats is more controversial. This study aimed to [...] Read more.
The treatment of choice for dermatitis herpetiformis (DH), a cutaneous manifestation of coeliac disease, is a life-long gluten-free diet (GFD). In a GFD, wheat, rye and barley should be strictly avoided, but the role of oats is more controversial. This study aimed to investigate the safety and long-term quality of life and health effects of oat consumption in 312 long-term treated DH patients. Baseline data were gathered from patient records and follow-up data from questionnaires or interviews, and validated questionnaires were used to assess quality of life. We found that altogether 256 patients (82%) were consuming oats as part of their GFD at the follow-up. Long-term follow-up data showed that there were no differences in the presence of long-term illnesses, coeliac disease complications or the usage of medication between those consuming and not consuming oats. However, oat consumers had a better quality of life and reported ongoing gastrointestinal symptoms less frequently (4% vs 19%, p = 0.004) at the follow-up than those not consuming oats. The study established that oats are safe for DH patients and in the long-term seem to improve the quality of life of DH patients. Full article
(This article belongs to the Special Issue Celiac Disease and Nonceliac Gluten Sensitivity: Update of the Pathophysiology, Diagnosis and Treatment)
10 pages, 637 KiB  
Article
Intestinal TG3- and TG2-Specific Plasma Cell Responses in Dermatitis Herpetiformis Patients Undergoing a Gluten Challenge
by Hanna Sankari, Minna Hietikko, Kalle Kurppa, Katri Kaukinen, Eriika Mansikka, Heini Huhtala, Kaija Laurila, Timo Reunala, Kaisa Hervonen, Teea Salmi and Katri Lindfors
Nutrients 2020, 12(2), 467; https://doi.org/10.3390/nu12020467 - 13 Feb 2020
Cited by 14 | Viewed by 3042
Abstract
Dermatitis herpetiformis (DH), a cutaneous manifestation of coeliac disease, is characterized by transglutaminase (TG) 3-targeted dermal immunoglobulin A (IgA) deposits. The treatment for DH is the same as for coeliac disease, namely a life-long gluten-free diet. DH patients typically have gluten-dependent circulating autoantibodies [...] Read more.
Dermatitis herpetiformis (DH), a cutaneous manifestation of coeliac disease, is characterized by transglutaminase (TG) 3-targeted dermal immunoglobulin A (IgA) deposits. The treatment for DH is the same as for coeliac disease, namely a life-long gluten-free diet. DH patients typically have gluten-dependent circulating autoantibodies targeting TG3 and TG2, and plasma cells secreting such autoantibodies have been detected in the small intestinal mucosa. This study investigates the gluten-responsiveness of intestinal TG3 and TG2 antibody-secreting plasma cells in 16 treated DH patients undergoing a gluten challenge. The frequency of both plasma cell populations increased significantly during the challenge, and their frequency correlated with the corresponding serum autoantibody levels at post-challenge. TG3-specific plasma cells were absent in all 18 untreated coeliac disease patients and seven non-coeliac control subjects on gluten-containing diets. These findings indicate that, in DH, both intestinal TG3- and TG2-antibody secreting plasma cells are gluten-dependent, and that TG3-antibody secreting plasma cells are DH-specific. Full article
(This article belongs to the Special Issue Celiac Disease and Nonceliac Gluten Sensitivity: Update of the Pathophysiology, Diagnosis and Treatment)
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16 pages, 3266 KiB  
Article
Stimulatory Response of Celiac Disease Peripheral Blood Mononuclear Cells Induced by RNAi Wheat Lines Differing in Grain Protein Composition
by Susana Sánchez-León, María José Giménez, Isabel Comino, Carolina Sousa, Miguel Ángel López Casado, María Isabel Torres and Francisco Barro
Nutrients 2019, 11(12), 2933; https://doi.org/10.3390/nu11122933 - 3 Dec 2019
Cited by 8 | Viewed by 3155
Abstract
Wheat gluten proteins are responsible for the bread-making properties of the dough but also for triggering important gastrointestinal disorders. Celiac disease (CD) affects approximately 1% of the population in Western countries. The only treatment available is the strict avoidance of gluten in the [...] Read more.
Wheat gluten proteins are responsible for the bread-making properties of the dough but also for triggering important gastrointestinal disorders. Celiac disease (CD) affects approximately 1% of the population in Western countries. The only treatment available is the strict avoidance of gluten in the diet. Interference RNA (RNAi) is an excellent approach for the down-regulation of genes coding for immunogenic proteins related to celiac disease, providing an alternative for the development of cereals suitable for CD patients. In the present work, we report a comparative study of the stimulatory capacity of seven low-gluten RNAi lines differing in grain gluten and non-gluten protein composition, relevant for CD and other gluten pathologies. Peripheral blood mononuclear cells (PBMCs) of 35 patients with active CD were included in this study to assess the stimulatory response induced by protein extracts from the RNAi lines. Analysis of the proliferative response and interferon-gamma (INF-γ) release of PBMCs demonstrated impaired stimulation in response to all RNAi lines. The lower response was provided by lines with a very low content of α- and γ-gliadins, and low or almost devoid of DQ2.5 and p31–43 α-gliadin epitopes. The non-gluten protein seems not to play a key role in PBMC stimulation. Full article
(This article belongs to the Special Issue Celiac Disease and Nonceliac Gluten Sensitivity: Update of the Pathophysiology, Diagnosis and Treatment)
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12 pages, 1686 KiB  
Article
CX3CL1–CX3CR1 Axis: A New Player in Coeliac Disease Pathogenesis
by Marta Fernández-Prieto, María Jesús Fernández-Aceñero, Natalia López-Palacios, Andrés Bodas, Sergio Farrais, David Cuevas, Virginia Pascual, M. Ángeles Cerón-Nieto, Saúl Horta-Herrera, Laura Espino-Paisán, Isabel Salazar and Concepción Núñez
Nutrients 2019, 11(11), 2551; https://doi.org/10.3390/nu11112551 - 23 Oct 2019
Cited by 8 | Viewed by 3175
Abstract
Background: The CX3CL1–CX3CR1 axis has been related to numerous diseases. The aim of our study was to investigate its involvement in coeliac disease (CD) pathogenesis, particularly in the early phase of the disease. Methods: We collected peripheral blood from CD patients and controls, [...] Read more.
Background: The CX3CL1–CX3CR1 axis has been related to numerous diseases. The aim of our study was to investigate its involvement in coeliac disease (CD) pathogenesis, particularly in the early phase of the disease. Methods: We collected peripheral blood from CD patients and controls, enrolled in a 3-day gluten challenge, to study soluble CX3CL1, I-TAC and MIG by Luminex, CX3CL1 and CX3CR1 gene expression by qPCR, and CX3CR1 protein expression in monocytes and CD8+, CD4+ and γδ+ T cells, by flow cytometry. We also analysed the expression of the CX3CL1 and CX3CR1 mRNA and protein in the duodenal biopsies of CD patients with active and treated disease, and in non-CD control individuals, by qPCR and immunohistochemistry. Results: After the gluten challenge, increased levels of CX3CL1, I-TAC and MIG proteins were observed in the peripheral blood of CD patients, with no changes in CX3CL1 mRNA, or CX3CR1 mRNA and protein. Regarding duodenal tissue, CX3CL1 was absent or barely present in the superficial and basal epithelium of CD patients, contrasting with the moderate to high levels present in controls. Conclusions: CX3CL1 seems to be involved in the appearance and progression of CD, and it appears to be a potential diagnostic biomarker. Its use as an alternative therapeutic target in CD deserves further research. Full article
(This article belongs to the Special Issue Celiac Disease and Nonceliac Gluten Sensitivity: Update of the Pathophysiology, Diagnosis and Treatment)
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