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Tye‐Din JA. Evolution in coeliac disease diagnosis and management. JGH Open 2024; 8:e13107. [PMID: 38957478 PMCID: PMC11217771 DOI: 10.1002/jgh3.13107] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Revised: 05/04/2024] [Accepted: 05/28/2024] [Indexed: 07/04/2024]
Abstract
The traditional gut-centric view of coeliac disease is evolving as immune and genetic insights underscore the central importance of a systemic, T cell immune response to gluten in disease pathogenesis. As the field increasingly recognize the limitations of small intestinal histology as the diagnostic standard, data supporting the accuracy of an immune (serologic) diagnosis of coeliac disease - well demonstrated in children - are growing for adults. Novel biomarkers such as interleukin-2 that identify the gluten-specific T cell demonstrate high sensitivity and specificity for coeliac disease and offer the potential for a diagnostic approach that avoids the need for gluten challenge. Asymptomatic disease and manifestations outside the gut pose considerable challenges for diagnosis using a case-finding strategy and enthusiasm for population screening is growing. The gluten-free diet remains a highly restrictive treatment and there is a paucity of controlled data to inform a safe gluten intake threshold. Ongoing symptoms and enteropathy are common and require systematic evaluation. Slowly-responsive disease is prevalent in the older patient diagnosed with coeliac disease, and super-sensitivity to gluten is an emerging concept that may explain many cases of nonresponsive disease. While there is great interest in developing novel therapies for coeliac disease, no drug has yet been registered. Efficacy studies are generally assessing drugs in patients with treated coeliac disease who undergo gluten challenge or in patients with nonresponsive disease; however, substantial questions remain around specific endpoints relevant for patients, clinicians and regulatory agencies and optimal trial design. Novel immune tools are providing informative readouts for clinical trials and are now shaping their design.
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Affiliation(s)
- Jason A Tye‐Din
- Immunology DivisionWalter and Eliza Hall InstituteParkvilleVictoriaAustralia
- Department of Medical BiologyUniversity of MelbourneParkvilleVictoriaAustralia
- Department of GastroenterologyThe Royal Melbourne HospitalParkvilleVictoriaAustralia
- Centre for Food & Allergy ResearchThe Murdoch Children's Research InstituteParkvilleVictoriaAustralia
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2
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Djorgbenoo R, Hu J, Hu C, Sang S. Fermented Oats as a Novel Functional Food. Nutrients 2023; 15:3521. [PMID: 37630712 PMCID: PMC10459665 DOI: 10.3390/nu15163521] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Revised: 08/03/2023] [Accepted: 08/07/2023] [Indexed: 08/27/2023] Open
Abstract
Fermented oats are gaining popularity due to their nutritional value and the increasing consumer demand for health-conscious foods. These oats are believed to offer enhanced phytochemical and nutritional profiles compared to unfermented oats. The increased nutritional content of fermented oats is associated with various health benefits, including anti-inflammatory and antioxidant activities, which could potentially reduce the risk of chronic diseases. Further investigations are warranted to elucidate the nutritional benefits of fermented oats in human nutrition. This mini review provides a comprehensive overview of fermented oat products available on the market and the various production methods employed for fermenting oats. Furthermore, this review investigates how fermentation affects the chemical composition and biological functions of oats. Additionally, this manuscript presents some future perspectives on fermented oat products by discussing potential research directions and opportunities for further development. The findings presented in this review contribute to the expanding body of knowledge on fermented oats as a promising functional food, paving the way for future studies and applications in the field of nutrition and health.
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Affiliation(s)
| | | | | | - Shengmin Sang
- Laboratory for Functional Foods and Human Health, Center for Excellence in Post-Harvest Technologies, North Carolina Research Campus, North Carolina Agricultural and Technical State University, Kannapolis, NC 28081, USA; (R.D.); (J.H.); (C.H.)
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3
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Rubio-Tapia A, Hill ID, Semrad C, Kelly CP, Greer KB, Limketkai BN, Lebwohl B. American College of Gastroenterology Guidelines Update: Diagnosis and Management of Celiac Disease. Am J Gastroenterol 2023; 118:59-76. [PMID: 36602836 DOI: 10.14309/ajg.0000000000002075] [Citation(s) in RCA: 167] [Impact Index Per Article: 83.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Accepted: 08/23/2022] [Indexed: 01/06/2023]
Abstract
This guideline presents an update to the 2013 American College of Gastroenterology Guideline on the Diagnosis and Management of Celiac Disease with updated recommendations for the evaluation and management of patients with celiac disease (CD). CD is defined as a permanent immune-mediated response to gluten present in wheat, barley, and rye. CD has a wide spectrum of clinical manifestations that resemble a multisystemic disorder rather than an isolated intestinal disease, and is characterized by small bowel injury and the presence of specific antibodies. Detection of CD-specific antibodies (e.g., tissue transglutaminase) in the serum is very helpful for the initial screening of patients with suspicion of CD. Intestinal biopsy is required in most patients to confirm the diagnosis. A nonbiopsy strategy for the diagnosis of CD in selected children is suggested and discussed in detail. Current treatment for CD requires strict adherence to a gluten-free diet (GFD) and lifelong medical follow-up. Most patients have excellent clinical response to a GFD. Nonresponsive CD is defined by persistent or recurrent symptoms despite being on a GFD. These patients require a systematic workup to rule out specific conditions that may cause persistent or recurrent symptoms, especially unintentional gluten contamination. Refractory CD is a rare cause of nonresponsive CD often associated with poor prognosis.
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Affiliation(s)
- Alberto Rubio-Tapia
- Division of Gastroenterology, Hepatology, and Nutrition, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - Ivor D Hill
- Division of Gastroenterology, Hepatology, and Nutrition, Nationwide Children Hospital, Columbus, Ohio, USA
| | - Carol Semrad
- Division of Gastroenterology, University of Chicago, Chicago, Illinois, USA
| | - Ciarán P Kelly
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
| | - Katarina B Greer
- Department of Medicine, Section of Gastroenterology and Hepatology, Louis Stokes VA Medical Center, Cleveland, Ohio, USA
| | - Berkeley N Limketkai
- Division of Digestive Diseases, UCLA School of Medicine, Los Angeles, California, USA
| | - Benjamin Lebwohl
- Division of Gastroenterology and Hepatology, Columbia University, New York, USA
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Donnelly SC. Extensive Mucosal Disease: Coeliac Disease and Eosinophilic Enteritis. INTESTINAL FAILURE 2023:161-175. [DOI: 10.1007/978-3-031-22265-8_12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Tye‐Din JA. Review article: Follow-up of coeliac disease. Aliment Pharmacol Ther 2022; 56 Suppl 1:S49-S63. [PMID: 35815829 PMCID: PMC9542881 DOI: 10.1111/apt.16847] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Revised: 02/12/2022] [Accepted: 02/13/2022] [Indexed: 12/09/2022]
Abstract
Coeliac disease is a lifelong immune-mediated enteropathy with systemic features associated with increased morbidity and modestly increased mortality. Treatment with a strict gluten-free diet improves symptoms and mucosal damage but is not curative and low-level gluten intake is common despite strict attempts at adherence. Regular follow-up after diagnosis is considered best-practice however this is executed poorly in the community with the problem compounded by the paucity of data informing optimal approaches. The aim of dietary treatment is to resolve symptoms, reduce complication risk and improve quality of life. It follows that the goals of monitoring are to assess dietary adherence, monitor disease activity, assess symptoms and screen for complications. Mucosal disease remission is regarded a key measure of treatment success as healing is associated with positive health outcomes. However, persistent villous atrophy is common, even after many years of a gluten-free diet. As the clinical significance of asymptomatic enteropathy is uncertain the role for routine follow-up biopsies remains contentious. Symptomatic non-responsive coeliac disease is common and with systematic follow-up a cause is usually found. Effective models of care involving the gastroenterologist, dietitian and primary care doctor will improve the consistency of long-term management and likely translate into better patient outcomes. Identifying suitable treatment targets linked to long-term health is an important goal.
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Affiliation(s)
- J. A. Tye‐Din
- Immunology DivisionThe Walter and Eliza Hall InstituteParkvilleVictoriaAustralia,Department of Medical BiologyUniversity of MelbourneParkvilleVictoriaAustralia,Department of GastroenterologyThe Royal Melbourne HospitalParkvilleVictoriaAustralia,Centre for Food & Allergy ResearchMurdoch Children’s Research InstituteParkvilleVictoriaAustralia
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Bouchard J, Valookaran AF, Aloud BM, Raj P, Malunga LN, Thandapilly SJ, Netticadan T. Impact of oats in the prevention/management of hypertension. Food Chem 2022; 381:132198. [PMID: 35123221 DOI: 10.1016/j.foodchem.2022.132198] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2021] [Revised: 01/16/2022] [Accepted: 01/17/2022] [Indexed: 12/24/2022]
Abstract
Oats are a rich source of a soluble fibre, beta-glucan, phenolic compounds, as well as functional lipid and protein components that could potentially aid in preventing and managing hypertension. Processing techniques commonly used to manufacture oat based foods have been shown to improve its physiological efficacy. Hypertension is a common condition that is a risk factor for cardiovascular disease, a primary cause of mortality worldwide. Though exercise and pharmacological interventions are often used in the management of hypertension, diet is an incredibly important factor. One preclinical study and a handful of clinical studies have shown that oat components/products are effective in lowering blood pressure. However, research in this area is limited and more studies are needed to elucidate the anti-hypertensive potential of oats.
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Affiliation(s)
- Jenny Bouchard
- Richardson Center for Functional Foods and Nutraceuticals, Winnipeg, MB, Canada; Department of Food and Human Nutritional Sciences, University of Manitoba, Winnipeg, MB, Canada; Morden Research and Development Centre, Agriculture and Agri-Food Canada, Morden, MB, Canada
| | - Aleena Francis Valookaran
- Morden Research and Development Centre, Agriculture and Agri-Food Canada, Morden, MB, Canada; Canadian Centre for Agri-Food Research in Health and Medicine , Winnipeg, MB, Canada
| | | | - Pema Raj
- Morden Research and Development Centre, Agriculture and Agri-Food Canada, Morden, MB, Canada; Canadian Centre for Agri-Food Research in Health and Medicine , Winnipeg, MB, Canada
| | - Lovemore Nkhata Malunga
- Richardson Center for Functional Foods and Nutraceuticals, Winnipeg, MB, Canada; Department of Food and Human Nutritional Sciences, University of Manitoba, Winnipeg, MB, Canada; Morden Research and Development Centre, Agriculture and Agri-Food Canada, Morden, MB, Canada
| | - Sijo Joseph Thandapilly
- Richardson Center for Functional Foods and Nutraceuticals, Winnipeg, MB, Canada; Department of Food and Human Nutritional Sciences, University of Manitoba, Winnipeg, MB, Canada; Morden Research and Development Centre, Agriculture and Agri-Food Canada, Morden, MB, Canada.
| | - Thomas Netticadan
- Morden Research and Development Centre, Agriculture and Agri-Food Canada, Morden, MB, Canada; Canadian Centre for Agri-Food Research in Health and Medicine , Winnipeg, MB, Canada; Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, MB, Canada.
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Gell G, Bugyi Z, Florides CG, Birinyi Z, Réder D, Szegő Z, Mucsi E, Schall E, Ács K, Langó B, Purgel S, Simon K, Varga B, Vida G, Veisz O, Tömösközi S, Békés F. Investigation of Protein and Epitope Characteristics of Oats and Its Implications for Celiac Disease. Front Nutr 2021; 8:702352. [PMID: 34660657 PMCID: PMC8511309 DOI: 10.3389/fnut.2021.702352] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Accepted: 08/23/2021] [Indexed: 12/14/2022] Open
Abstract
The use of pure oats (oats cultivated with special care to avoid gluten contamination from wheat, rye, and barley) in the gluten-free diet (GFD) represents important nutritional benefits for the celiac consumer. However, emerging evidence suggests that some oat cultivars may contain wheat gliadin analog polypeptides. Consequently, it is necessary to screen oats in terms of protein and epitope composition to be able to select safe varieties for gluten-free applications. The overall aim of our study is to investigate the variability of oat protein composition directly related to health-related and techno-functional properties. Elements of an oat sample population representing 162 cultivated varieties from 20 countries and the protein composition of resulting samples have been characterized. Size distribution of the total protein extracts has been analyzed by size exclusion-high performance liquid chromatography (SE-HPLC) while the 70% ethanol-extracted proteins were analyzed by RP-HPLC. Protein extracts separated into three main groups of fractions on the SE-HPLC column: polymeric proteins, avenins (both containing three subgroups based on their size), and soluble proteins, representing respectively 68.79–86.60, 8.86–27.72, and 2.89–11.85% of the total protein content. The ratio of polymeric to monomeric proteins varied between 1.37 and 3.73. Seventy-six reversed phase-HPLC-separated peaks have been differentiated from the ethanol extractable proteins of the entire population. Their distribution among the cultivars varied significantly, 6–23 peaks per cultivar. The number of appearances of peaks also showed large variation: one peak has been found in 107 samples, while 15 peaks have been identified, which appeared in less than five cultivars. An estimation method for ranking the avenin-epitope content of the samples has been developed by using MS spectrometric data of collected RP-HPLC peaks and bioinformatics methods. Using ELISA methodology with the R5 antibody, a high number of the investigated samples were found to be contaminated with wheat, barley, or rye.
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Affiliation(s)
- Gyöngyvér Gell
- Department of Biological Resources, Agricultural Institute, Centre for Agricultural Research, EötvösLoránd Research Network, Martonvásár, Hungary.,Department of Applied Biotechnology and Food Science, Research Group of Cereal Science and Food Quality, Budapest University of Technology and Economics, Budapest, Hungary
| | - Zsuzsanna Bugyi
- Department of Applied Biotechnology and Food Science, Research Group of Cereal Science and Food Quality, Budapest University of Technology and Economics, Budapest, Hungary
| | | | - Zsófia Birinyi
- Department of Biological Resources, Agricultural Institute, Centre for Agricultural Research, EötvösLoránd Research Network, Martonvásár, Hungary
| | - Dalma Réder
- Department of Biological Resources, Agricultural Institute, Centre for Agricultural Research, EötvösLoránd Research Network, Martonvásár, Hungary
| | - Zsuzsanna Szegő
- Department of Applied Biotechnology and Food Science, Research Group of Cereal Science and Food Quality, Budapest University of Technology and Economics, Budapest, Hungary
| | - Edina Mucsi
- Department of Applied Biotechnology and Food Science, Research Group of Cereal Science and Food Quality, Budapest University of Technology and Economics, Budapest, Hungary
| | - Eszter Schall
- Department of Applied Biotechnology and Food Science, Research Group of Cereal Science and Food Quality, Budapest University of Technology and Economics, Budapest, Hungary
| | - Katalin Ács
- Cereal Research Non-Profit Ltd., Szeged, Hungary
| | | | | | | | - Balázs Varga
- Cereal Breeding Department, Agricultural Institute, Centre for Agricultural Research, EötvösLoránd Research Network, Martonvásár, Hungary
| | - Gyula Vida
- Cereal Breeding Department, Agricultural Institute, Centre for Agricultural Research, EötvösLoránd Research Network, Martonvásár, Hungary
| | - Ottó Veisz
- Cereal Breeding Department, Agricultural Institute, Centre for Agricultural Research, EötvösLoránd Research Network, Martonvásár, Hungary
| | - Sándor Tömösközi
- Department of Applied Biotechnology and Food Science, Research Group of Cereal Science and Food Quality, Budapest University of Technology and Economics, Budapest, Hungary
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8
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Valido E, Stoyanov J, Bertolo A, Hertig-Godeschalk A, Zeh RM, Flueck JL, Minder B, Stojic S, Metzger B, Bussler W, Muka T, Kern H, Glisic M. Systematic Review of the Effects of Oat Intake on Gastrointestinal Health. J Nutr 2021; 151:3075-3090. [PMID: 34486656 DOI: 10.1093/jn/nxab245] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Revised: 04/27/2021] [Accepted: 06/28/2021] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Oats are a food source with multiple health benefits that could support beneficial bacterial groups and provide important bioactive compounds for the gut. OBJECTIVES This review explores the association between oat intake, gastrointestinal (GI) symptoms, and microbial community changes in individuals with celiac disease (CeD), irritable bowel syndrome (IBS), and inflammatory bowel disease (IBD) and without GI disease. METHODS Four databases and Google Scholar were systematically searched from inception until April 29, 2021. Clinical trials, observational studies, and in vitro studies with human gut-derived samples were included. RESULTS There were 84 articles [23 randomized controlled trials (RCTs), 21 nonrandomized trials, 8 observational studies, and 32 in vitro studies] included. Oat intake increased total bacterial count, Lactobacilli spp., and Bifidobacterium spp. in healthy individuals and those with CeD. There was an increased concentration of short-chain fatty acids and improved gut permeability with oat intake but with no significant quality-of-life difference. In some individuals with CeD, consumption of certain oat types was associated with worsening of GI symptoms. We found no studies reporting on IBS and only 3 for IBD. The quality of RCTs showed some concerns mostly in domains of randomization (73.9%), whereas the quality of evidence of non-RCTs, observational studies, and in vitro studies was satisfactory. CONCLUSIONS Oat intake was associated with the increase of beneficial bacterial groups in individuals without GI disease and those with CeD. Most studies showed no changes in GI symptoms with oat consumption. In vitro studies in CeD provide insight to oat-sensitive individuals and their GI mucosa, but the clinical studies remain limited, precluding our ability to draw firm conclusions. The prevalence of oat sensitivity in individuals with CeD should be further explored as this could improve clinical management and facilitate inclusion of oat in the diet for this population.
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Affiliation(s)
- Ezra Valido
- Swiss Paraplegic Research, Nottwil, Switzerland
- Department of Health Sciences, University of Lucerne, Lucerne, Switzerland
| | | | | | | | | | | | - Beatrice Minder
- Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland
| | - Stevan Stojic
- Department of Health Sciences, University of Lucerne, Lucerne, Switzerland
| | - Brandon Metzger
- Standard Process Nutrition Innovation Center, Kannapolis, NC, USA
| | - Weston Bussler
- Standard Process Nutrition Innovation Center, Kannapolis, NC, USA
| | - Taulant Muka
- Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland
| | - Hua Kern
- Standard Process Nutrition Innovation Center, Kannapolis, NC, USA
| | - Marija Glisic
- Swiss Paraplegic Research, Nottwil, Switzerland
- Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland
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Ranking of immunodominant epitopes in celiac disease: Identification of reliable parameters for the safety assessment of innovative food proteins. Food Chem Toxicol 2021; 157:112584. [PMID: 34582965 DOI: 10.1016/j.fct.2021.112584] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2021] [Revised: 08/30/2021] [Accepted: 09/22/2021] [Indexed: 01/25/2023]
Abstract
A ranking of gluten T-cell epitopes triggering celiac disease (CD) for its potential application in the safety assessment of innovative food proteins is developed. This ranking takes into account clinical relevance and information derived from key steps involved in the CD pathogenic pathway: enzymatic digestion, epitope binding to HLA-DQ receptors of the antigen-presenting cells and activation of pro-inflammatory CD4 T-cells, which recognizes the HLA-DQ-epitope complex and initiates the inflammatory response. In silico chymotrypsin digestion was the most discriminatory tool for the ranking of gluten T-cell epitopes among all digestive enzymes studied, classifying 81% and 60% of epitopes binding HLA-DQ2.5 and HLA-DQ8 molecules, respectively, with a high risk. A positive relationship between the number of prolines and the risk of gluten T-cell epitopes was identified. HLA-binding data analysis revealed the additional role played by the flanking regions of the 9-mer epitopes whereas the integration of T-cell activation data into the ranking strategy was incomplete because it was difficult to combine results from different studies. The overall ranking proposed in decreasing order of immunological relevance was: α-gliadins > ω-gliadins > hordeins > γ-gliadins ∼ avenins ∼ secalins > glutenins. This novel approach can be considered as a first step to reshape the risk assessment strategy of innovative proteins and their potential to trigger CD.
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A Novel Sprouted Oat Fermented Beverage: Evaluation of Safety and Health Benefits for Celiac Individuals. Nutrients 2021; 13:nu13082522. [PMID: 34444682 PMCID: PMC8401588 DOI: 10.3390/nu13082522] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Revised: 07/20/2021] [Accepted: 07/21/2021] [Indexed: 12/12/2022] Open
Abstract
The safety and health effects for celiac people of a novel beverage (SOFB) developed from sprouted oat flour by fermentation with Lactobacillus plantarum was explored. In vitro reactivity against anti-gliadin antibodies (AGA) and antioxidant/anti-inflammatory potential of SOFB in RAW 264.7 macrophages and Caco-2 cells were evaluated. Immunoreactivity against AGA and antioxidant activity were not detected in SOFB, but it exhibited significant anti-inflammatory activity. The tolerability and impact of SOFB consumption for 6 months on nutritional status and intestinal microbiota composition were investigated in 10 celiac adults (five treated and five control). SOFB consumption did not adversely affect duodenal mucosa nor the total IgA or anti-tissue transglutaminase antibody (IgA-tTG) levels in celiac participants, but it significantly decreased total cholesterol levels at all sampling times and folic acid levels at the end of the study compared to the placebo beverage. SOFB administration also shifted gut microbiota, leading to a higher relative abundance of some beneficial bacteria including the genera Subdoligranulum, Ruminococcus and Lactobacillus in the SOFB group. This study provides supporting evidence of the safety of health benefits of a novel functional beverage produced from sprouted oat.
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Colombo F, Di Lorenzo C, Biella S, Bani C, Restani P. Ancient and Modern Cereals as Ingredients of the Gluten-Free Diet: Are They Safe Enough for Celiac Consumers? Foods 2021; 10:foods10040906. [PMID: 33924221 PMCID: PMC8074585 DOI: 10.3390/foods10040906] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Revised: 04/14/2021] [Accepted: 04/17/2021] [Indexed: 02/05/2023] Open
Abstract
Celiac disease is an autoimmune disorder that occurs in genetically predisposed individuals after consuming prolamins from some cereals. Although the products available for celiac subjects have increased significantly in quality and quantity over the last few decades, research still focuses on identifying new ingredients to improve the nutritional, sensorial and functional qualities of gluten-free products. In terms of toxicity for people with celiac disease, there is a wide variability between ancient and modern grains. The most contradictory results are related to the role of oats in the gluten-free diet. In order to clarify the role of minor cereals (such as oat) and ancient grains in the diets of celiac patients, this review discusses recent in vitro and in vivo studies performed on those cereals for which the toxicity for celiac subjects is still controversial. According to in vivo studies, selected oat varieties could be tolerated by celiac patients. On the other hands, although some wheat-ancient grains (Triticum monococcum, Triticum aestivum ssp. spelta and Kamut®) showed a reduced in vitro toxicity, to date, these grains are still considered toxic for celiac patients. Contradictory results underline the importance of studying the safety of "unusual" cereals in more detail.
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12
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Mumolo MG, Rettura F, Melissari S, Costa F, Ricchiuti A, Ceccarelli L, de Bortoli N, Marchi S, Bellini M. Is Gluten the Only Culprit for Non-Celiac Gluten/Wheat Sensitivity? Nutrients 2020; 12:E3785. [PMID: 33321805 PMCID: PMC7762999 DOI: 10.3390/nu12123785] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2020] [Revised: 12/05/2020] [Accepted: 12/07/2020] [Indexed: 12/12/2022] Open
Abstract
The gluten-free diet (GFD) has gained increasing popularity in recent years, supported by marketing campaigns, media messages and social networks. Nevertheless, real knowledge of gluten and GF-related implications for health is still poor among the general population. The GFD has also been suggested for non-celiac gluten/wheat sensitivity (NCG/WS), a clinical entity characterized by intestinal and extraintestinal symptoms induced by gluten ingestion in the absence of celiac disease (CD) or wheat allergy (WA). NCG/WS should be regarded as an "umbrella term" including a variety of different conditions where gluten is likely not the only factor responsible for triggering symptoms. Other compounds aside from gluten may be involved in the pathogenesis of NCG/WS. These include fructans, which are part of fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs), amylase trypsin inhibitors (ATIs), wheat germ agglutinin (WGA) and glyphosate. The GFD might be an appropriate dietary approach for patients with self-reported gluten/wheat-dependent symptoms. A low-FODMAP diet (LFD) should be the first dietary option for patients referring symptoms more related to FODMAPs than gluten/wheat and the second-line treatment for those with self-reported gluten/wheat-related symptoms not responding to the GFD. A personalized approach, regular follow-up and the help of a skilled dietician are mandatory.
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Affiliation(s)
| | - Francesco Rettura
- Gastrointestinal Unit, Department of Translational Sciences and New Technologies in Medicine and Surgery, University of Pisa, 56124 Pisa, Italy; (M.G.M.); (S.M.); (F.C.); (A.R.); (L.C.); (N.d.B.); (S.M.); (M.B.)
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13
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Nyachoti S, Adebayo S, Godebo TR. Elemental composition of teff (a gluten-free grain), maize and wheat: Staple crops in the Main Ethiopian Rift Valley. J Food Compost Anal 2020; 100. [PMID: 34366562 DOI: 10.1016/j.jfca.2020.103660] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Teff, maize, and wheat are the major cereals grown in volcanic ash-rich soils of the Main Ethiopian Rift (MER) Valley. Teff is a gluten-free cereal native to Ethiopia, used for making a local flat bread called injera, and is getting popularity globally due to its nutritional value (gluten-free and high fiber content). Teff can thus be an alternative diet for the treatment of celiac disease, a lifelong intolerance to gluten. This study aims to assess the distribution of toxic and essential elements in these staple cereals using Inductively Coupled Plasma Mass Spectrometry (ICP-MS) and compare with mineral composition of wheat, and maize consumed in the Main Ethiopian Rift Valley. We found significantly higher mean concentrations (in mg/kg) of Mg (1400), Ca (1210), Na (33), Fe (159), Mn (71), Sr (5.6), and Cu (4.8) in teff compared to wheat and maize. Maize had the lowest concentrations of these essential elements. Mean concentrations (in μg/kg) of As (24.7) and Pb (70) in teff were relatively higher compared to wheat and maize, which had similar values of As (4.5) and Pb (8.9). Teff and wheat had similar Cd concentrations (in μg/kg) of 4.8 and 5.4 respectively compared to maize (1.5). Cadmium concentrations were below the Codex standard established for Cd in cereal grains (100 μg/kg). Only one teff sample exceeded the Codex standard set for Pb (200 μg/kg) in cereal grains. This study provides information on nutritional values and food safety of maize, wheat, and teff; the latter is becoming an alternative gluten-free diet for celiac patients in countries where wheat is commonly a staple food.
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Affiliation(s)
- Syprose Nyachoti
- Department of Environmental Health Sciences, Tulane University, New Orleans, LA, 70112, USA
| | - Segun Adebayo
- Department of Earth and Environmental Sciences, Tulane University, New Orleans, LA, 70118, USA
| | - Tewodros Rango Godebo
- Department of Environmental Health Sciences, Tulane University, New Orleans, LA, 70112, USA
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Marasco G, Cirota GG, Rossini B, Lungaro L, Di Biase AR, Colecchia A, Volta U, De Giorgio R, Festi D, Caio G. Probiotics, Prebiotics and Other Dietary Supplements for Gut Microbiota Modulation in Celiac Disease Patients. Nutrients 2020; 12:2674. [PMID: 32887325 PMCID: PMC7551848 DOI: 10.3390/nu12092674] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2020] [Revised: 08/27/2020] [Accepted: 08/28/2020] [Indexed: 02/06/2023] Open
Abstract
To date, the only available treatment for celiac disease (CD) patients is a life-lasting gluten-free diet (GFD). Lack of adherence to the GFD leads to a significant risk of adverse health consequences. Food cross-contamination, nutritional imbalances, and persistent gastrointestinal symptoms are the main concerns related to GFD. Moreover, despite rigid compliance to GFD, patients struggle in achieving a full restoring of the gut microbiota, which plays a role in the nutritive compounds processing, and absorption. Pivotal studies on the supplementation of GFD with probiotics, such as Bifidobacterium and Lactobacilli, reported a potential to restore gut microbiota composition and to pre-digest gluten in the intestinal lumen, reducing the inflammation associated with gluten intake, the intestinal permeability, and the cytokine and antibody production. These findings could explain an improvement in symptoms and quality of life in patients treated with GFD and probiotics. On the other hand, the inclusion of prebiotics in GFD could also be easy to administer and cost-effective as an adjunctive treatment for CD, having the power to stimulate the growth of potentially health-promoting bacteria strains. However, evidence regarding the use of prebiotics and probiotics in patients with CD is still insufficient to justify their use in clinical practice.
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Affiliation(s)
- Giovanni Marasco
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Via Massarenti 9, 40138 Bologna, Italy; (G.G.C.); (B.R.); (U.V.); (D.F.)
| | - Giovanna Grazia Cirota
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Via Massarenti 9, 40138 Bologna, Italy; (G.G.C.); (B.R.); (U.V.); (D.F.)
| | - Benedetta Rossini
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Via Massarenti 9, 40138 Bologna, Italy; (G.G.C.); (B.R.); (U.V.); (D.F.)
| | - Lisa Lungaro
- Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, 44124 Ferrara, Italy; (L.L.); (R.D.G.)
| | - Anna Rita Di Biase
- Department of Pediatrics, Policlinic Hospital, University of Modena, Via del Pozzo 71, 41126 Modena, Italy;
| | - Antonio Colecchia
- Gastroenterology Unit, Borgo Trento University Hospital of Verona, P.le Aristide Stefani 1, 37126 Verona, Italy;
| | - Umberto Volta
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Via Massarenti 9, 40138 Bologna, Italy; (G.G.C.); (B.R.); (U.V.); (D.F.)
| | - Roberto De Giorgio
- Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, 44124 Ferrara, Italy; (L.L.); (R.D.G.)
| | - Davide Festi
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Via Massarenti 9, 40138 Bologna, Italy; (G.G.C.); (B.R.); (U.V.); (D.F.)
| | - Giacomo Caio
- Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, 44124 Ferrara, Italy; (L.L.); (R.D.G.)
- Celiac Center and Mucosal Immunology and Biology Research, Massachusetts General Hospital-Harvard Medical School, Boston, MA 02114, USA
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15
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Ahola HG, Sontag-Strohm TS, Schulman AH, Tanhuanpää P, Viitala S, Huang X. Immunochemical analysis of oat avenins in an oat cultivar and landrace collection. J Cereal Sci 2020. [DOI: 10.1016/j.jcs.2020.103053] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
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16
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Affiliation(s)
- James J Ashton
- Department of Paediatric Gastroenterology, Southampton Children's Hospital, Southampton SO16 6YD, UK
- Department of Human Genetics and Genomics, University of Southampton, Southampton, UK
| | - Rebecca Smith
- Department of Gastroenterology, University Hospital Southampton, Southampton, UK
| | - Trevor Smith
- Department of Gastroenterology, University Hospital Southampton, Southampton, UK
| | - R Mark Beattie
- Department of Paediatric Gastroenterology, Southampton Children's Hospital, Southampton SO16 6YD, UK
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17
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Kosová K, Leišová-Svobodová L, Dvořáček V. Oats as a Safe Alternative to Triticeae Cereals for People Suffering from Celiac Disease? A Review. PLANT FOODS FOR HUMAN NUTRITION (DORDRECHT, NETHERLANDS) 2020; 75:131-141. [PMID: 32133597 DOI: 10.1007/s11130-020-00800-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
Oats represent a promising alternative to small-grain cereals from Triticeae group (wheat, barley, rye) for persons suffering from any form of gluten intolerance, especially celiac disease (CD), since oat-specific prolamins avenins reveal generally lower gluten content and immunoreactivity. Recent studies on avenin molecular structure revealed large genetic variability in avenin sequences affecting the spectrum of gluten peptides produced by hydrolases in human digestive tract. The aim of the present review is to summarise recent knowledge obtained in laboratory studies focused on the effect of avenin-derived peptides on reactivity of crucial components of human immune system such as dendritic cells (DC) and T-cells. The other part of the review summarises the results of clinical studies with CD patients including oat products in their diet. Since different clinical studies revealed contradictory results regarding potential safety of oats for CD patients, the focus has to be directed at genetic variability in oat avenins. Identification of avenin isoforms with minimum CD immunoreactivity will open up ways leading to designing novel oat cultivars suitable for CD patients. Knowledge on immunoreactivity of gluten peptides together with breeding new oat cultivars revealing minimum avenin immunoreactivity with respect to CD as well as application of food processing technologies leading to gluten content reduction should result in development of gluten-free oats safe for celiacs.
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Affiliation(s)
- Klára Kosová
- Division of Crop Genetics and Breeding, Crop Research Institute, Prague, 6-Ruzyně, Czechia.
| | | | - Václav Dvořáček
- Division of Crop Genetics and Breeding, Crop Research Institute, Prague, 6-Ruzyně, Czechia
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18
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The Long-Term Safety and Quality of Life Effects of Oats in Dermatitis Herpetiformis. Nutrients 2020; 12:nu12041060. [PMID: 32290504 PMCID: PMC7230654 DOI: 10.3390/nu12041060] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2020] [Revised: 04/03/2020] [Accepted: 04/09/2020] [Indexed: 12/20/2022] Open
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 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.
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19
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Naegeli H, Bresson J, Dalmay T, Dewhurst IC, Epstein MM, Firbank LG, Guerche P, Hejatko J, Moreno FJ, Mullins E, Nogué F, Rostoks N, Sánchez Serrano JJ, Savoini G, Veromann E, Veronesi F, Álvarez F, Ardizzone M, Dumont AF, Devos Y, Gennaro A, Gómez Ruiz JÁ, Lanzoni A, Neri FM, Paraskevopoulos K. Assessment of genetically modified soybean SYHT0H2 for food and feed uses, import and processing, under Regulation (EC) No 1829/2003 (application EFSA-GMO-DE-2012-111). EFSA J 2020; 18:e05946. [PMID: 32626498 PMCID: PMC7008876 DOI: 10.2903/j.efsa.2020.5946] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
The scope of application EFSA-GMO-DE-2012-111 is for food and feed uses, import and processing of genetically modified (GM) soybean SYHT0H2 in the European Union. Soybean SYHT0H2 was developed to confer tolerance to the herbicidal active substances mesotrione and other p-hydroxyphenylpyruvate dioxygenase (HPPD)-inhibiting herbicides and glufosinate ammonium. The molecular characterisation data and bioinformatic analyses do not identify issues except for sequence similarity of AvHPPD-03 to bacterial haemolysins that was considered in food/feed safety assessment. The outcome of the comparative analysis (agronomic/phenotypic and compositional characteristics) did not need further assessment except for the changes in seed levels of α-tocopherol and γ-tocopherol that were assessed for food and feed relevance. The GMO Panel does not identify toxicological and allergenicity concerns for the AvHPPD-03 and PAT proteins expressed in soybean SYHT0H2 and finds no evidence that the genetic modification would change the overall allergenicity of soybean SYHT0H2. The nutritional impact of food/feed from soybean SYHT0H2 is expected to be the same as that of food/feed from the conventional counterpart and commercial non-GM soybean reference varieties. The GMO Panel concludes that soybean SYHT0H2 is as safe as and nutritionally equivalent to the conventional counterpart and the tested non-GM soybean reference varieties, and no post-market monitoring of food/feed is considered necessary. In the case of accidental release of viable soybean SYHT0H2 grains into the environment, soybean SYHT0H2 would not raise environmental safety concerns. The post-market environmental monitoring plan and reporting intervals are in line with the intended uses of soybean SYHT0H2. In conclusion, the GMO Panel considers that soybean SYHT0H2, as described in this application, is as safe as its conventional counterpart and the tested non-GM soybean reference varieties with respect to potential effects on human and animal health and the environment.
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20
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Tanner G, Juhász A, Florides CG, Nye-Wood M, Békés F, Colgrave ML, Russell AK, Hardy MY, Tye-Din JA. Preparation and Characterization of Avenin-Enriched Oat Protein by Chill Precipitation for Feeding Trials in Celiac Disease. Front Nutr 2019; 6:162. [PMID: 31681788 PMCID: PMC6803533 DOI: 10.3389/fnut.2019.00162] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2019] [Accepted: 09/26/2019] [Indexed: 12/15/2022] Open
Abstract
The safety of oats for people with celiac disease remains unresolved. While oats have attractive nutritional properties that can improve the quality and palatability of the restrictive, low fiber gluten-free diet, rigorous feeding studies to address their safety in celiac disease are needed. Assessing the oat prolamin proteins (avenins) in isolation and controlling for gluten contamination and other oat components such as fiber that can cause non-specific effects and symptoms is crucial. Further, the avenin should contain all reported immunogenic T cell epitopes, and be deliverable at a dose that enables biological responses to be correlated with clinical effects. To date, isolation of a purified food-grade avenin in sufficient quantities for feeding studies has not been feasible. Here, we report a new gluten isolation technique that enabled 2 kg of avenin to be extracted from 400 kg of wheat-free oats under rigorous gluten-free and food grade conditions. The extract consisted of 85% protein of which 96% of the protein was avenin. The concentration of starch (1.8% dry weight), β-glucan (0.2% dry weight), and free sugars (1.8% dry weight) were all low in the final avenin preparation. Other sugars including oligosaccharides, small fructans, and other complex sugars were also low at 2.8% dry weight. Liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis of the proteins in these preparations showed they consisted only of oat proteins and were uncontaminated by gluten containing cereals including wheat, barley or rye. Proteomic analysis of the avenin enriched samples detected more avenin subtypes and fewer other proteins compared to samples obtained using other extraction procedures. The identified proteins represented five main groups, four containing known immune-stimulatory avenin peptides. All five groups were identified in the 50% (v/v) ethanol extract however the group harboring the epitope DQ2.5-ave-1b was less represented. The avenin-enriched protein fractions were quantitatively collected by reversed phase HPLC and analyzed by MALDI-TOF mass spectrometry. Three reverse phase HPLC peaks, representing ~40% of the protein content, were enriched in proteins containing DQ2.5-ave-1a epitope. The resultant high quality avenin will facilitate controlled and definitive feeding studies to establish the safety of oat consumption by people with celiac disease.
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Affiliation(s)
- Greg Tanner
- School of Biosciences, University of Melbourne, Melbourne, VIC, Australia
| | - Angéla Juhász
- School of Science, Edith Cowan University, Joondalup, WA, Australia
| | | | | | | | | | - Amy K. Russell
- Immunology Division, The Walter and Eliza Hall Institute, Melbourne, VIC, Australia
- Department of Medical Biology, The University of Melbourne, Melbourne, VIC, Australia
| | - Melinda Y. Hardy
- Immunology Division, The Walter and Eliza Hall Institute, Melbourne, VIC, Australia
- Department of Medical Biology, The University of Melbourne, Melbourne, VIC, Australia
| | - Jason A. Tye-Din
- Immunology Division, The Walter and Eliza Hall Institute, Melbourne, VIC, Australia
- Department of Medical Biology, The University of Melbourne, Melbourne, VIC, Australia
- Department of Gastroenterology, The Royal Melbourne Hospital, Parkville, VIC, Australia
- Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, VIC, Australia
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21
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Hoffmanová I, Sánchez D, Szczepanková A, Tlaskalová-Hogenová H. The Pros and Cons of Using Oat in a Gluten-Free Diet for Celiac Patients. Nutrients 2019; 11:nu11102345. [PMID: 31581722 PMCID: PMC6835965 DOI: 10.3390/nu11102345] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2019] [Revised: 09/12/2019] [Accepted: 09/25/2019] [Indexed: 02/07/2023] Open
Abstract
A therapeutic gluten-free diet often has nutritional limitations. Nutritional qualities such as high protein content, the presence of biologically active and beneficial substances (fiber, beta-glucans, polyunsaturated fatty acids, essential amino acids, antioxidants, vitamins, and minerals), and tolerance by the majority of celiac patients make oat popular for use in gluten-free diet. The health risk of long-time consumption of oat by celiac patients is a matter of debate. The introduction of oat into the diet is only recommended for celiac patients in remission. Furthermore, not every variety of oat is also appropriate for a gluten-free diet. The risk of sensitization and an adverse immunologically mediated reaction is a real threat in some celiac patients. Several unsolved issues still exist which include the following: (1) determination of the susceptibility markers for the subgroup of celiac patients who are at risk because they do not tolerate dietary oat, (2) identification of suitable varieties of oat and estimating the safe dose of oat for the diet, and (3) optimization of methods for detecting the gliadin contamination in raw oat used in a gluten-free diet.
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Affiliation(s)
- Iva Hoffmanová
- 2nd Department of Internal Medicine, University Hospital Královské Vinohrady and Third Faculty of Medicine, Charles University, Ruská 87, 10000 Prague, Czech Republic.
| | - Daniel Sánchez
- Laboratory of Cellular and Molecular Immunology, Institute of Microbiology of the Czech Academy of Sciences, Vídeňská 1083, 14220 Prague, Czech Republic.
| | - Adéla Szczepanková
- Laboratory of Cellular and Molecular Immunology, Institute of Microbiology of the Czech Academy of Sciences, Vídeňská 1083, 14220 Prague, Czech Republic.
- First Faculty of Medicine, Charles University, Kateřinská 1660/32, 121 08 Prague, Czech Republic.
| | - Helena Tlaskalová-Hogenová
- Laboratory of Cellular and Molecular Immunology, Institute of Microbiology of the Czech Academy of Sciences, Vídeňská 1083, 14220 Prague, Czech Republic.
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22
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Spector Cohen I, Day AS, Shaoul R. To Be Oats or Not to Be? An Update on the Ongoing Debate on Oats for Patients With Celiac Disease. Front Pediatr 2019; 7:384. [PMID: 31616650 PMCID: PMC6775206 DOI: 10.3389/fped.2019.00384] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2019] [Accepted: 09/05/2019] [Indexed: 12/12/2022] Open
Abstract
To date, the only known effective treatment for celiac disease (CD) is a strict gluten-free diet (GFD) for life. Patients with CD often find it difficult to adhere to strict GFD. Oats, compared with wheat, barley, and rye, contain less amounts of prolamins. Inclusion of oats in a GFD might be valuable due to their nutritional and health benefits and increase of food variety. Therefore, they may potentially improve feeding diversity for these children and improve taste and satiety. We reviewed the literature to evaluate the safety of oats in CD patients. We have searched PUBMED, societal guidelines and national health authorities' recommendations. The following aspects were reviewed: gastrointestinal symptoms, malabsorption, serology including specific avenin antibodies, mucosal changes, avenin toxicity, immunogenicity of oats, and quality of life. We also referred to wheat contamination of oat products, the safe amount of oats for CD patients and the type of oats recommended. Data support that pure oats are well-tolerated by most CD patients, at moderate amounts (20-25 g/day dry rolled oats for children; 50-70 g/day for adults). Nevertheless, since the potential for sensitivity/toxicity exists, oats should be added with caution to a GFD, only after all CD symptoms including weight loss and growth disturbances have resolved, after at least 6 months of conventional GFD and probably also after normalization of serology. The need for pre exposure biopsy is unclear and should be considered on an individual basis.
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Affiliation(s)
- Inna Spector Cohen
- Pediatric Gastroenterology and Nutrition Institute, Ruth Children's Hospital of Haifa, Rambam Medical Center, Faculty of Medicine, Technion, Haifa, Israel
| | - Andrew S. Day
- Department of Paediatrics, University of Otago, Christchurch, New Zealand
| | - Ron Shaoul
- Pediatric Gastroenterology and Nutrition Institute, Ruth Children's Hospital of Haifa, Rambam Medical Center, Faculty of Medicine, Technion, Haifa, Israel
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23
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Jung KH, Shin D, Kim S, Min D, Kim W, Kim J, Lee G, Bae H. Intratracheal Ovalbumin Administration Induces Colitis Through the IFN-γ Pathway in Mice. Front Immunol 2019; 10:530. [PMID: 30949176 PMCID: PMC6437076 DOI: 10.3389/fimmu.2019.00530] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2018] [Accepted: 02/27/2019] [Indexed: 12/16/2022] Open
Abstract
Recent studies have reported an increased incidence of inflammatory bowel disease (IBD) in patients with pulmonary diseases. Despite clinical and epidemiological studies of the interplay between colitis and asthma, the diseases' related underlying mechanisms remain unclear. In this study, we evaluated the development of colitis in a model of allergic airway inflammation. We revealed that intratracheal chronic ovalbumin (OVA) exposure induces colitis and allergic airway inflammation. Interestingly, induction of colitis was largely regulated by Th1, rather than Th2 responses, whereas allergic airway inflammation was primarily mediated by Th2 responses. Experiments in Tbx21 (T-bet) and Ifng (IFN-γ) deficient mice have confirmed that IFN-γ is a major mediator involved in OVA-induced colitis. These findings broaden current understanding of allergen induced colitis pathology and could play a role in the development of novel clinical treatment strategies for asthmatic patients who are at risk of developing colitis.
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Affiliation(s)
- Kyoung-Hwa Jung
- Department of Physiology, College of Korean Medicine, Kyung Hee University, Seoul, South Korea
| | - Dasom Shin
- Department of Physiology, College of Korean Medicine, Kyung Hee University, Seoul, South Korea
| | - Sejun Kim
- Department of Physiology, College of Korean Medicine, Kyung Hee University, Seoul, South Korea
| | - Daeun Min
- Department of Physiology, College of Korean Medicine, Kyung Hee University, Seoul, South Korea
| | - Woogyeong Kim
- Department of Korean Physiology, College of Pharmacy, Kyung Hee University, Seoul, South Korea
| | - Jinju Kim
- Department of Korean Physiology, College of Pharmacy, Kyung Hee University, Seoul, South Korea
| | - Gihyun Lee
- College of Korean Medicine, Dongshin University, Naju, South Korea
| | - Hyunsu Bae
- Department of Physiology, College of Korean Medicine, Kyung Hee University, Seoul, South Korea
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24
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Smart CE, Annan F, Higgins LA, Jelleryd E, Lopez M, Acerini CL. ISPAD Clinical Practice Consensus Guidelines 2018: Nutritional management in children and adolescents with diabetes. Pediatr Diabetes 2018; 19 Suppl 27:136-154. [PMID: 30062718 DOI: 10.1111/pedi.12738] [Citation(s) in RCA: 123] [Impact Index Per Article: 17.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2018] [Accepted: 07/16/2018] [Indexed: 02/06/2023] Open
Affiliation(s)
- Carmel E Smart
- Department of Paediatric Endocrinology, John Hunter Children's Hospital, Newcastle, NSW, Australia.,School of Health Sciences, University of Newcastle, Newcastle, NSW, Australia
| | | | | | | | | | - Carlo L Acerini
- Department of Paediatrics, University of Cambridge, Cambridge, UK
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25
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Fritz RD, Chen Y. Oat safety for celiac disease patients: theoretical analysis correlates adverse symptoms in clinical studies to contaminated study oats. Nutr Res 2018; 60:54-67. [PMID: 30527260 DOI: 10.1016/j.nutres.2018.09.003] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2018] [Revised: 08/29/2018] [Accepted: 09/11/2018] [Indexed: 02/07/2023]
Abstract
Inclusion of oats in a gluten-free (GF) diet can provide whole grain nutritional benefits to celiac disease (CD) patients, but there has been debate regarding oat safety for these individuals. This is because of conflicting research findings, with inconsistencies attributed to varying CD subject's sensitivities to "pure" oats. Clinical trials to date have assumed oats provided to subjects to be lightly contaminated, if at all. This assumption is challenged here since oat's propensity to be "kernel" contaminated with gluten sources like wheat and barley has recently been shown to significantly complicate confirmation of a GF state. We therefore hypothesize that clinical studies may have inadvertently provided pill-like gluten kernels intermittently to study subjects, leading to adverse outcomes that could potentially explain inconsistencies between study conclusions. To test this theory, potential gluten contamination of oats used in a cross-section of 12 important oat feeding studies has been estimated, done according to descriptions of oats used, published contamination rates for various oat types, and study oat dosages. Expected gluten exposures were found to be at levels to elicit clinical effects in a large portion of CD patients, correlating with observed clinical reaction rates in those studies (P value = .0006). Estimated gluten doses were found insufficient, however, to affect morphological outcomes, whereas only 1 study had 1 case. Our analysis provides a new perspective with which to view oat safety study conclusions and justifies new clinical trials using today's higher-purity GF oats to settle the oat safety for CD patient debate.
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Affiliation(s)
- Ronald D Fritz
- PepsiCo R&D Measurement Sciences, 617 W Main St, Barrington, IL 60010, USA.
| | - Yumin Chen
- PepsiCo R&D Measurement Sciences, 617 W Main St, Barrington, IL 60010, USA
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26
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Boschetto D, Mirzaei H, Leong RWL, Tarroni G, Grisan E. Semiautomatic detection of villi in confocal endoscopy for the evaluation of celiac disease. ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY. IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY. ANNUAL INTERNATIONAL CONFERENCE 2018; 2015:8143-6. [PMID: 26738184 DOI: 10.1109/embc.2015.7320284] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
Celiac Disease (CD) is an immune-mediated enteropathy, diagnosed in the clinical practice by intestinal biopsy and the concomitant presence of a positive celiac serology. Confocal Laser Endomicroscopy (CLE) allows skilled and trained experts to potentially perform in vivo virtual histology of small-bowel mucosa. In particular, it allows the qualitative evaluation of mucosa alteration such as a decrease in goblet cells density, presence of villous atrophy or crypt hypertrophy. We present a semi-automatic method for villi detection from confocal endoscopy images, whose appearance change in case of villous atrophy. Starting from a set of manual seeds, a first rough segmentation of the villi is obtained by means of mathematical morphology operations. A merge and split procedure is then performed, to ensure that each seed originates a different region in the final segmentation. A border refinement process is finally performed, evolving the shape of each region according to local gradient intensities. Mean and median Dice coefficients for 290 villi originating from 66 images when compared to manually obtained ground truth are 80.71% and 87.96% respectively.
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27
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Lionetti E, Gatti S, Galeazzi T, Caporelli N, Francavilla R, Cucchiara S, Roggero P, Malamisura B, Iacono G, Tomarchio S, Kleon W, Restani P, Brusca I, Budelli A, Gesuita R, Carle F, Catassi C. Safety of Oats in Children with Celiac Disease: A Double-Blind, Randomized, Placebo-Controlled Trial. J Pediatr 2018; 194:116-122.e2. [PMID: 29478494 DOI: 10.1016/j.jpeds.2017.10.062] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2017] [Revised: 09/04/2017] [Accepted: 10/26/2017] [Indexed: 12/26/2022]
Abstract
OBJECTIVE To evaluate the long-term validity and safety of pure oats in the treatment of children with celiac disease. STUDY DESIGN This noninferiority clinical trial used a double-blind, placebo-controlled, crossover design extended over 15 months. Three hundred six children with a biopsy-proven diagnosis of celiac disease on a gluten-free diet for ≥2 years were randomly assigned to eat specifically prepared gluten-free food containing an age-dependent amount (15-40 g) of either placebo or purified nonreactive varieties of oats for 2 consecutive 6-month periods separated by washout standard gluten-free diet for 3 months. Clinical (body mass index, Gastrointestinal Symptoms Rating Scale score), serologic (IgA antitransglutaminase antibodies, and IgA anti-avenin antibodies), and intestinal permeability data were measured at baseline, and after 6, 9, and 15 months. Direct treatment effect was evaluated by a nonparametric approach using medians (95% CI) as summary statistic. RESULTS After the exclusion of 129 patients who dropped out, the cohort included 177 children (79 in the oats-placebo and 98 in the placebo-oats group; median, 0.004; 95% CI, -0.0002 to 0.0089). Direct treatment effect was not statistically significant for clinical, serologic, and intestinal permeability variables (body mass index: median, -0.5; 95% CI, -0.12 to 0.00; Gastrointestinal Symptoms Rating Scale score: median, 0; 95% CI, -2.5 to 0.00; IgA antitransglutaminase antibodies: median, -0.02; 95% CI, -0.25 to 0.23; IgA anti-avenin antibodies: median, -0.0002; 95% CI, -0.0007 to 0.0003; intestinal permeability test: median, 0.004; 95% CI, -0.0002 to 0.0089). CONCLUSIONS Pure nonreactive oat products are a safe dietary choice in the treatment of children with celiac disease. TRIAL REGISTRATION ClinicalTrials.gov: NCT00808301.
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Affiliation(s)
- Elena Lionetti
- Department of Pediatrics, Marche Polytechnic University, Ancona, Italy.
| | - Simona Gatti
- Department of Pediatrics, Marche Polytechnic University, Ancona, Italy
| | - Tiziana Galeazzi
- Department of Pediatrics, Marche Polytechnic University, Ancona, Italy
| | - Nicole Caporelli
- Department of Pediatrics, Marche Polytechnic University, Ancona, Italy
| | | | | | - Paola Roggero
- Neonatal Intensive Care Unit, Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
| | - Basilio Malamisura
- Department of Pediatrics, S. Maria dell'Olmo Hospital Cava de' Tirreni, University Hospital of Salerno, Italy
| | - Giuseppe Iacono
- Pediatric Gastroenterology Unit, "G. Di Cristina" Children Hospital, Palermo, Italy
| | | | - Wolfgang Kleon
- Department of Pediatrics, Bolzano Hospital, Bolzano, Italy
| | - Patrizia Restani
- Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy
| | - Ignazio Brusca
- Clinical Pathology Laboratory, Buccheri La Ferla Hospital, Palermo, Italy
| | | | - Rosaria Gesuita
- Center of Epidemiology, Biostatistics and Medical Information Technology, Marche Polytechnic University, Ancona, Italy
| | - Flavia Carle
- Center of Epidemiology, Biostatistics and Medical Information Technology, Marche Polytechnic University, Ancona, Italy
| | - Carlo Catassi
- Department of Pediatrics, Marche Polytechnic University, Ancona, Italy
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Dawson C, Mendoza-Porras O, Byrne K, Hooper T, Howitt C, Colgrave M. Oat of this world: Defining peptide markers for detection of oats in processed food. Pept Sci (Hoboken) 2018. [DOI: 10.1002/pep2.24045] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Affiliation(s)
- Charlotte Dawson
- CSIRO Agriculture and Food; 306 Carmody Road; St Lucia QLD 4067 Australia
| | | | - Keren Byrne
- CSIRO Agriculture and Food; 306 Carmody Road; St Lucia QLD 4067 Australia
| | - Thomas Hooper
- CSIRO Agriculture and Food; 306 Carmody Road; St Lucia QLD 4067 Australia
| | - Crispin Howitt
- CSIRO Agriculture and Food; GPO Box 1700; Canberra ACT 2601 Australia
| | - Michelle Colgrave
- CSIRO Agriculture and Food; 306 Carmody Road; St Lucia QLD 4067 Australia
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Tye-Din JA, Galipeau HJ, Agardh D. Celiac Disease: A Review of Current Concepts in Pathogenesis, Prevention, and Novel Therapies. Front Pediatr 2018; 6:350. [PMID: 30519552 PMCID: PMC6258800 DOI: 10.3389/fped.2018.00350] [Citation(s) in RCA: 92] [Impact Index Per Article: 13.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2018] [Accepted: 10/29/2018] [Indexed: 12/14/2022] Open
Abstract
Our understanding of celiac disease and how it develops has evolved significantly over the last half century. Although traditionally viewed as a pediatric illness characterized by malabsorption, it is now better seen as an immune illness with systemic manifestations affecting all ages. Population studies reveal this global disease is common and, in many countries, increasing in prevalence. These studies underscore the importance of specific HLA susceptibility genes and gluten consumption in disease development and suggest that other genetic and environmental factors could also play a role. The emerging data on viral and bacterial microbe-host interactions and their alterations in celiac disease provides a plausible mechanism linking environmental risk and disease development. Although the inflammatory lesion of celiac disease is complex, the strong HLA association highlights a central role for pathogenic T cells responding to select gluten peptides that have now been defined for the most common genetic form of celiac disease. What remains less understood is how loss of tolerance to gluten occurs. New insights into celiac disease are now providing opportunities to intervene in its development, course, diagnosis, and treatment.
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Affiliation(s)
- Jason A Tye-Din
- Immunology Division, The Walter and Eliza Hall Institute, Parkville, VIC, Australia.,Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia.,Department of Gastroenterology, The Royal Melbourne Hospital, Parkville, VIC, Australia.,Centre for Food & Allergy Research, Murdoch Children's Research Institute, Parkville, VIC, Australia
| | - Heather J Galipeau
- Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - Daniel Agardh
- The Diabetes and Celiac Disease Unit, Department of Clinical Sciences, Lund University, Malmö, Sweden.,Unit of Endocrinology and Gastroenterology, Department of Pediatrics, Skåne University Hospital, Malmö, Sweden
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30
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Oats in healthy gluten-free and regular diets: A perspective. Food Res Int 2017; 110:3-10. [PMID: 30029703 DOI: 10.1016/j.foodres.2017.11.031] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2017] [Revised: 11/11/2017] [Accepted: 11/19/2017] [Indexed: 12/11/2022]
Abstract
During the 20th century, the economic position of oats (Avena sativa L.) decreased strongly in favour of higher yielding crops including winter wheat and maize. Presently, oat represents only ~1.3% of the total world grain production, and its production system is fragmented. Nonetheless, current interest is growing because of recent knowledge on its potential benefits in food, feed and agriculture. This perspective will serve as a further impetus, with special focus on the recently valued advantages of oats in human food and health. Five approved European Food Safety Authority (EFSA) health claims apply to oats. Four relate to the oat-specific soluble fibres, the beta-glucans, and concern the maintenance and reduction of blood cholesterol, better blood glucose balance and increased faecal bulk. The fifth claim concerns the high content of unsaturated fatty acids, especially present in the endosperm, which reduces the risks of heart and vascular diseases. Furthermore, oat starch has a low glycemic index, which is favourable for weight control. Oat-specific polyphenols and avenanthramides have antioxidant and anti-inflammatory properties. Thus, oats can contribute significantly to the presently recommended whole-grain diet. Next to globulins, oats contain a small fraction of prolamin storage proteins, called 'avenins', but at a much lower quantity than gluten proteins in wheat, barley and rye. Oat avenins do not contain any of the known coeliac disease epitopes from gluten of wheat, barley and rye. Long-term food studies confirm the safety of oats for coeliac disease patients and the positive health effects of oat products in a gluten-free diet. These effects are general and independent of oat varieties. In the EU (since 2009), the USA (since 2013) and Canada (since 2015) oat products may be sold as gluten-free provided that any gluten contamination level is below 20ppm. Oats are, however, generally not gluten-free when produced in a conventional production chain, because of regular contamination with wheat, barley or rye. Therefore, establishing a separate gluten-free oat production chain requires controlling all steps in the chain; the strict conditions will be discussed. Genomic tools, including a single nucleotide polymorphism (SNP) marker array and a dense genetic map, have recently been developed and will support marker-assisted breeding. In 2015, the Oat Global initiative emerged enabling a world-wide cooperation starting with a data sharing facility on genotypic, metabolic and phenotypic characteristics. Further, the EU project TRAFOON (Traditional Food Networks) facilitated the transfer of knowledge to small- and medium-sized enterprises (SMEs) to stimulate innovations in oat production, processing, products and marketing, among others with regard to gluten-free. Finally, with focus on counteracting market fragmentation of the global oat market and production chains, interactive innovation strategies between customers (consumers) and companies through co-creation are discussed.
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Abstract
Objective and Conclusion: Uncertainty still exists about the use of oats and wheat starch as part of a gluten-free diet in patients with celiac disease (CD). This review should help to clarify the issues at hand. Whereas uncontaminated (from gluten/gliadin) oats and oats from cultivars not containing celiac-activating sequences of proline and glutamine can be used without risk of intestinal damage, wheat starch should not be used, unless it is free of gluten-that is, deglutinized-because even small amounts of gluten over time are able to induce small intestinal mucosal damage.
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Affiliation(s)
- J Rainer Poley
- a Eastern Virginia Medical School , Division of Pediatric Gastroenterology and Nutrition, Department of Pediatrics EVMS, and Childrens' Hospital of the King's Daughters , Norfolk , Virginia, (ret).,b Division of Pediatric Gastroenterology and Nutrition, Department of Pediatrics, Brody School of Medicine , East Carolina University , Greenville , North Carolina (ret)
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Lee G, Jung KH, Shin D, Lee C, Kim W, Lee S, Kim J, Bae H. Cigarette Smoking Triggers Colitis by IFN-γ + CD4 + T Cells. Front Immunol 2017; 8:1344. [PMID: 29163466 PMCID: PMC5671659 DOI: 10.3389/fimmu.2017.01344] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2017] [Accepted: 10/03/2017] [Indexed: 12/21/2022] Open
Abstract
The increased incidence of Crohn’s disease in smokers has been recently reported, suggesting a strong association of cigarette smoke (CS) with colitis. However, the mechanism of the action of CS on colitis has not yet been explored. Here, we demonstrate that CS exposure is sufficient to induce colitis in mice. Interestingly, the colitis is mainly mediated by Th1, but not Th17, responses. CD4+ T-cell depletion or T-bet/IFN-γ deficiency protects against the development of colitis induced by CS. Additionally, IFN-γ-producing CD4+ T cells play a substantial role in CS-induced colitis. The adoptive transfer (AT) of effector T cells from CS-exposed WT mice into colitis-prone mice caused these mice to develop colitis, while the AT of effector T cells from IFN-γ knock-out mice did not. These findings have implications for broadening our understanding of CS-induced pathology and for the development of novel therapeutic strategies to treat Crohn’s disease.
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Affiliation(s)
- Gihyun Lee
- Department of Science in Korean Medicine, Kyung Hee University, Seoul, South Korea
| | - Kyoung-Hwa Jung
- Department of Science in Korean Medicine, Kyung Hee University, Seoul, South Korea
| | - Dasom Shin
- Department of Science in Korean Medicine, Kyung Hee University, Seoul, South Korea
| | - Chanju Lee
- Department of Science in Korean Medicine, Kyung Hee University, Seoul, South Korea
| | - Woogyeong Kim
- Department of Korean Physiology, College of Pharmacy, Kyung Hee University, Seoul, South Korea
| | - Sujin Lee
- Department of Science in Korean Medicine, Kyung Hee University, Seoul, South Korea
| | - Jinju Kim
- Department of Korean Physiology, College of Pharmacy, Kyung Hee University, Seoul, South Korea
| | - Hyunsu Bae
- Department of Science in Korean Medicine, Kyung Hee University, Seoul, South Korea
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33
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Development and in-house validation of a competitive ELISA for the quantitative detection of gluten in food. Food Control 2017. [DOI: 10.1016/j.foodcont.2017.05.021] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
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Pinto-Sánchez MI, Causada-Calo N, Bercik P, Ford AC, Murray JA, Armstrong D, Semrad C, Kupfer SS, Alaedini A, Moayyedi P, Leffler DA, Verdú EF, Green P. Safety of Adding Oats to a Gluten-Free Diet for Patients With Celiac Disease: Systematic Review and Meta-analysis of Clinical and Observational Studies. Gastroenterology 2017; 153:395-409.e3. [PMID: 28431885 DOI: 10.1053/j.gastro.2017.04.009] [Citation(s) in RCA: 71] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2017] [Revised: 03/28/2017] [Accepted: 04/06/2017] [Indexed: 12/27/2022]
Abstract
BACKGROUND & AIMS Patients with celiac disease should maintain a gluten-free diet (GFD), excluding wheat, rye, and barley. Oats might increase the nutritional value of a GFD, but their inclusion is controversial. We performed a systematic review and meta-analysis to evaluate the safety of oats as part of a GFD in patients with celiac disease. METHODS We searched the Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE databases for clinical trials and observational studies of the effects of including oats in GFD of patients with celiac disease. The studies reported patients' symptoms, results from serology tests, and findings from histologic analyses. We used the GRADE approach to assess the quality of evidence. RESULTS We identified 433 studies; 28 were eligible for analysis. Of these, 6 were randomized and 2 were not randomized controlled trials comprising a total of 661 patients-the remaining studies were observational. All randomized controlled trials used pure/uncontaminated oats. Oat consumption for 12 months did not affect symptoms (standardized mean difference: reduction in symptom scores in patients who did and did not consume oats, -0.22; 95% CI, -0.56 to 0.13; P = .22), histologic scores (relative risk for histologic findings in patients who consumed oats, 0.24; 95% CI, 0.01-4.8; P = .35), intraepithelial lymphocyte counts (standardized mean difference, 0.21; 95% CI, reduction of 1.44 to increase in 1.86), or results from serologic tests. Subgroup analyses of adults vs children did not reveal differences. The overall quality of evidence was low. CONCLUSIONS In a systematic review and meta-analysis, we found no evidence that addition of oats to a GFD affects symptoms, histology, immunity, or serologic features of patients with celiac disease. However, there were few studies for many endpoints, as well as limited geographic distribution and low quality of evidence. Rigorous double-blind, placebo-controlled, randomized controlled trials, using commonly available oats sourced from different regions, are needed.
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Affiliation(s)
- María Inés Pinto-Sánchez
- Department of Medicine, Farncombe Family Digestive Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Natalia Causada-Calo
- Department of Medicine, Farncombe Family Digestive Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Premysl Bercik
- Department of Medicine, Farncombe Family Digestive Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Alexander C Ford
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, United Kingdom; Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, United Kingdom
| | - Joseph A Murray
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - David Armstrong
- Department of Medicine, Farncombe Family Digestive Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Carol Semrad
- Celiac Disease Center at University of Chicago Medicine, Chicago, Illinois
| | - Sonia S Kupfer
- Celiac Disease Center at University of Chicago Medicine, Chicago, Illinois
| | - Armin Alaedini
- Celiac Disease Center at Columbia University, New York, New York
| | - Paul Moayyedi
- Department of Medicine, Farncombe Family Digestive Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Daniel A Leffler
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, Massachusetts
| | - Elena F Verdú
- Department of Medicine, Farncombe Family Digestive Research Institute, McMaster University, Hamilton, Ontario, Canada.
| | - Peter Green
- Celiac Disease Center at Columbia University, New York, New York
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Chen Y, Fritz RD, Kock L, Garg D, Davis RM, Kasturi P. A stepwise, 'test-all-positives' methodology to assess gluten-kernel contamination at the serving-size level in gluten-free (GF) oat production. Food Chem 2017; 240:391-395. [PMID: 28946288 DOI: 10.1016/j.foodchem.2017.07.153] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2017] [Revised: 07/22/2017] [Accepted: 07/28/2017] [Indexed: 01/29/2023]
Abstract
A step-wise, 'test-all-positive-gluten' analytical methodology has been developed and verified to assess kernel-based gluten contamination (i.e., wheat, barley and rye kernels) during gluten-free (GF) oat production. It targets GF claim compliance at the serving-size level (of a pouch or approximately 40-50g). Oat groats are collected from GF oat production following a robust attribute-based sampling plan then split into 75-g subsamples, and ground. R-Biopharm R5 sandwich ELISA R7001 is used for analysis of all the first15-g portions of the ground sample. A >20-ppm result disqualifies the production lot, while a >5 to <20-ppm result triggers complete analysis of the remaining 60-g of ground sample, analyzed in 15-g portions. If all five 15-g test results are <20ppm, and their average is <10.67ppm (since a 20-ppm contaminant in 40g of oats would dilute to 10.67ppm in 75-g), the lot is passed.
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Affiliation(s)
- Yumin Chen
- PepsiCo, Inc. Global R&D Measurement Sciences, 617 W. Main Street, Barrington, IL 60010, USA
| | - Ronald D Fritz
- PepsiCo, Inc. Global R&D Measurement Sciences, 617 W. Main Street, Barrington, IL 60010, USA.
| | - Lindsay Kock
- PepsiCo, Inc. Global R&D Measurement Sciences, 617 W. Main Street, Barrington, IL 60010, USA
| | - Dinesh Garg
- PepsiCo, Inc. Milling R&D, 418 2ndStreet NE, Cedar Rapids, IA 52401, USA
| | - R Mark Davis
- PepsiCo, Inc. Global R&D Food Safety, 617 W. Main Street, Barrington, IL 60010, USA
| | - Prabhakar Kasturi
- PepsiCo, Inc. Global R&D Measurement Sciences, 617 W. Main Street, Barrington, IL 60010, USA
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Aaltonen K, Laurikka P, Huhtala H, Mäki M, Kaukinen K, Kurppa K. The Long-Term Consumption of Oats in Celiac Disease Patients Is Safe: A Large Cross-Sectional Study. Nutrients 2017; 9:E611. [PMID: 28617328 PMCID: PMC5490590 DOI: 10.3390/nu9060611] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2017] [Revised: 06/09/2017] [Accepted: 06/12/2017] [Indexed: 12/20/2022] Open
Abstract
A strict gluten-free diet (GFD) can be diversified by non-contaminated oats, but there is a shortage of long-term studies concerning its safety. We compared long-term treatment outcomes and factors associated with the introduction of oats between celiac patients on a GFD with or without oats. Eight hundred sixty-nine previously diagnosed celiac patients were interviewed. The validated Gastrointestinal Symptom Rating Scale (GSRS), Psychological General Well-Being (PGWB), and Short-Form 36 Health Survey (SF-36) questionnaires were used to assess symptoms and quality of life, serological tests were performed, and results of histology were confirmed from patient records. We found the median duration of GFD to be 10 years and 82% using oats. Factors predicting the consumption of oats were diagnosis after the year 2000, advice from a dietitian, detection by screening, and mild clinical presentation. Oat consumers and non-consumers did not differ in dietary adherence (96.5% vs. 97.4%, p = 0.746), the prevalence of symptoms (22.9% vs. 22.5%, p = 0.931), positivity for endomysial antibodies (8.8% vs. 6.0%, p = 0.237), histological recovery after one year (63.1% vs. 60.0%, p = 0.773), malignancy (4.8% vs. 3.3%, p = 0.420), osteoporosis/osteopenia (9.2% vs. 11.0%, p = 0.489), or fractures (26.9% vs. 27.9%, p = 0.791). The oat consumers had better SF-36 physical role limitations and general health scores. Based on our results, the long-term consumption of oats in celiac disease patients is safe and may improve quality of life.
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Affiliation(s)
- Katri Aaltonen
- Center for Child Health Research, Tampere University Hospital, 33521 Tampere, Finland.
- The Faculty of Medicine and Life Sciences, University of Tampere, 33014 Tampere, Finland.
| | - Pilvi Laurikka
- Celiac Disease Research Centre, Tampere University Hospital, 33521 Tampere, Finland.
| | - Heini Huhtala
- Faculty of Social Sciences, University of Tampere, 33014 Tampere, Finland.
| | - Markku Mäki
- Center for Child Health Research, Tampere University Hospital, 33521 Tampere, Finland.
| | - Katri Kaukinen
- The Faculty of Medicine and Life Sciences, University of Tampere, 33014 Tampere, Finland.
- Celiac Disease Research Centre, Tampere University Hospital, 33521 Tampere, Finland.
- Department of Internal Medicine, Tampere University Hospital, 33521 Tampere, Finland.
| | - Kalle Kurppa
- Center for Child Health Research, Tampere University Hospital, 33521 Tampere, Finland.
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Naegeli H, Birch AN, Casacuberta J, De Schrijver A, Gralak MA, Guerche P, Jones H, Manachini B, Messéan A, Nielsen EE, Nogué F, Robaglia C, Rostoks N, Sweet J, Tebbe C, Visioli F, Wal JM, Eigenmann P, Epstein M, Hoffmann-Sommergruber K, Koning F, Lovik M, Mills C, Moreno FJ, van Loveren H, Selb R, Fernandez Dumont A. Guidance on allergenicity assessment of genetically modified plants. EFSA J 2017; 15:e04862. [PMID: 32728397 PMCID: PMC7384481 DOI: 10.2903/j.efsa.2017.4862] [Citation(s) in RCA: 96] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
This document provides supplementary guidance on specific topics for the allergenicity risk assessment of genetically modified plants. In particular, it supplements general recommendations outlined in previous EFSA GMO Panel guidelines and Implementing Regulation (EU) No 503/2013. The topics addressed are non-IgE-mediated adverse immune reactions to foods, in vitro protein digestibility tests and endogenous allergenicity. New scientific and regulatory developments regarding these three topics are described in this document. Considerations on the practical implementation of those developments in the risk assessment of genetically modified plants are discussed and recommended, where appropriate.
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Benoit L, Masiri J, Del Blanco IA, Meshgi M, Gendel SM, Samadpour M. Assessment of Avenins from Different Oat Varieties Using R5-Based Sandwich ELISA. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2017; 65:1467-1472. [PMID: 28141922 DOI: 10.1021/acs.jafc.6b05105] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/06/2023]
Abstract
Gluten derived from wheat and related triticeae cereals possesses distinct amino acid sequences that provoke the immunopathogenic features of celiac disease (CD) in genetically susceptible individuals. However, the role of oat-derived gluten, or avenins, in CD pathogenesis remains a disputed matter, as evidenced by a lack in harmonized legislation regarding gluten classification in relation to gluten-free labeling. In this study, we have analyzed a panel of pure oat cultivars using a sandwich ELISA based on the R5 monoclonal antibody (mAb), which binds to canonical epitopes occurring within celiagenic peptides present in triticeae-derived gluten but reportedly not present in avenins. We have identified three varieties of oats that reproducibly bind R5 antibodies and levels indicating the presence of gluten at more than the 20 ppm gluten regulatory threshold. Nested assessment using Western blot analysis and alternative gluten detection systems corroborated these results. Collectively, these data suggest that select oat varieties may prove problematic to patients with CD and to food companies and regulatory agencies and will extend our basic understanding of current gluten detection systems.
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Affiliation(s)
- Lora Benoit
- IEH Laboratories and Consulting Group, Inc. (IEH) , 15300 Bothell Way N.E., Lake Forest Park, Washington 98155, United States
- Department of Biology, California State University-Fresno , Fresno, California 93740, United States
| | - Jongkit Masiri
- Molecular Epidemiology, Inc. (MEI) , 15300 Bothell Way N.E., Lake Forest Park, Washington 98155, United States
| | - Isabel A Del Blanco
- Department of Plant Sciences, University of California , One Shields Avenue, Davis, California 95616, United States
| | - Mahzad Meshgi
- Molecular Epidemiology, Inc. (MEI) , 15300 Bothell Way N.E., Lake Forest Park, Washington 98155, United States
| | - Steven M Gendel
- IEH Laboratories and Consulting Group, Inc. (IEH) , 15300 Bothell Way N.E., Lake Forest Park, Washington 98155, United States
| | - Mansour Samadpour
- IEH Laboratories and Consulting Group, Inc. (IEH) , 15300 Bothell Way N.E., Lake Forest Park, Washington 98155, United States
- Molecular Epidemiology, Inc. (MEI) , 15300 Bothell Way N.E., Lake Forest Park, Washington 98155, United States
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Abstract
Gluten is the main storage protein of wheat grains. Gluten is a complex mixture of hundreds of related but distinct proteins, mainly gliadin and glutenin. Similar storage proteins exist as secalin in rye, hordein in barley, and avenins in oats and are collectively referred to as "gluten." The objective was to discuss the biochemical and functional properties of the gluten proteins, including structure, sources, and dietary intakes. Literature was reviewed from food science and nutrition journals. The gluten protein networks vary because of different components and sizes, and variability caused by genotype, growing conditions, and technological processes. The structures and interactions of this matrix contribute to the unique properties of gluten. The resulting functions are essential to determining the dough quality of bread and other baked products. Gluten is heat stable and has the capacity to act as a binding and extending agent and is commonly used as an additive in processed foods for improved texture, moisture retention, and flavor. Gliadin contains peptide sequences that are highly resistant to gastric, pancreatic, and intestinal proteolytic digestion in the gastrointestinal tract. The average daily gluten intake in a Western diet is thought to be 5-20 g/day and has been implicated in several disorders. Gluten containing grains (wheat, rye, barley, and oats) are important staple foods. Gluten is among the most complex protein networks and plays a key role in determining the rheological dough properties.
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Giménez MJ, Real A, García-Molina MD, Sousa C, Barro F. Characterization of celiac disease related oat proteins: bases for the development of high quality oat varieties suitable for celiac patients. Sci Rep 2017; 7:42588. [PMID: 28209962 PMCID: PMC5314403 DOI: 10.1038/srep42588] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2016] [Accepted: 01/11/2017] [Indexed: 12/16/2022] Open
Abstract
Some studies have suggested that the immunogenicity of oats depends on the cultivar. RP-HPLC has been proposed as a useful technique to select varieties of oats with reduced immunogenicity. The aim of this study was to identify both the avenin protein patterns associated with low gluten content and the available variability for the development of new non-toxic oat cultivars. The peaks of alcohol-soluble avenins of a collection of landraces and cultivars of oats have been characterized based on the RP-HPLC elution times. The immunotoxicity of oat varieties for patients with celiac disease (CD) has been tested using a competitive ELISA based on G12 monoclonal antibody. The oat lines show, on average, seven avenin peaks giving profiles with certain similarities. Based on this similarity, most of the accessions have been grouped into avenin patterns. The variability of RP-HPLC profiles of the collection is great, but not sufficient to uniquely identify the different varieties of the set. Overall, the immunogenicity of the collection is less than 20 ppm. However, there is a different distribution of toxicity ranges between the different peak patterns. We conclude that the RP-HPLC technique is useful to establish groups of varieties differing in degree of toxicity for CD patients.
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Affiliation(s)
| | - Ana Real
- INSERM U1218 "ACTION", Bordeaux University, Bordeaux Cedex, France
| | | | - Carolina Sousa
- Departamento de Microbiología y Parasitología, Facultad de Farmacia, Universidad de Sevilla, Sevilla, Spain
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Fritz RD, Chen Y, Contreras V. Gluten-containing grains skew gluten assessment in oats due to sample grind non-homogeneity. Food Chem 2017; 216:170-5. [DOI: 10.1016/j.foodchem.2016.08.031] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2016] [Revised: 08/08/2016] [Accepted: 08/10/2016] [Indexed: 02/07/2023]
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Gilissen LJWJ, van der Meer IM, Smulders MJM. Why Oats Are Safe and Healthy for Celiac Disease Patients. Med Sci (Basel) 2016; 4:medsci4040021. [PMID: 29083384 PMCID: PMC5635790 DOI: 10.3390/medsci4040021] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2016] [Revised: 11/09/2016] [Accepted: 11/21/2016] [Indexed: 12/12/2022] Open
Abstract
The water-insoluble storage proteins of cereals (prolamins) are called “gluten” in wheat, barley, and rye, and “avenins” in oat. Gluten can provoke celiac disease (CD) in genetically susceptible individuals (those with human leukocyte antigen (HLA)-DQ2 or HLA-DQ8 serotypes). Avenins are present at a lower concentration (10%–15% of total protein content) in oat as compared to gluten in wheat (80%–85%). The avenins in the genus Avena (cultivated oat as well as various wild species of which gene bank accessions were analyzed) are free of the known CD immunogenic epitopes from wheat, barley, and rye. T cells that recognize avenin-specific epitopes have been found very rarely in CD patients. CD patients that consume oats daily do not show significantly increased levels of intraepithelial lymphocyte (EIL) cells. The safety and the positive health effects of the long-term inclusion of oats in the gluten-free diet have been confirmed in long-term studies. Since 2009 (EC 41/2009) and 2013 (FDA) oat products may be sold as gluten-free in several countries provided a gluten contamination level below 20 ppm. Introduction of oats in the gluten-free diet of celiac patients is advised after the recovery of the intestine. Health effects of oat consumption are reflected in European Food Safety Authority (EFSA)- and Food and Drug Administration (FDA)-approved health claims. Oats can form a healthy, nutritious, fiber-rich, and safe complement to the gluten-free diet.
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Affiliation(s)
- Luud J W J Gilissen
- Wageningen University & Research, Bioscience, 6700 AA Wageningen, The Netherlands.
| | | | - Marinus J M Smulders
- Wageningen University & Research, Plant Breeding, 6700 AA Wageningen, The Netherlands.
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Fritz RD, Chen Y. Kernel-based gluten contamination of gluten-free oatmeal complicates gluten assessment as it causes binary-like test outcomes. Int J Food Sci Technol 2016. [DOI: 10.1111/ijfs.13288] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Affiliation(s)
- Ronald D. Fritz
- PepsiCo Global R&D Measurement Sciences; 617 W. Main Street Barrington IL 60010 USA
| | - Yumin Chen
- PepsiCo Global R&D Measurement Sciences; 617 W. Main Street Barrington IL 60010 USA
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45
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Wahab WA, Šuligoj T, Ellis J, Côrtez-Real B, Ciclitira PJ. Coeliac disease: immunogenicity studies of barley hordein and rye secalin-derived peptides. Int J Exp Pathol 2016; 97:303-309. [PMID: 27659035 PMCID: PMC5061761 DOI: 10.1111/iep.12199] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2016] [Accepted: 07/27/2016] [Indexed: 12/31/2022] Open
Abstract
Coeliac disease (CD) is an inflammatory disorder of the small intestine. It includes aberrant adaptive immunity with presentation of CD toxic gluten peptides by HLA-DQ2 or DQ8 molecules to gluten-sensitive T cells. A ω-gliadin/C-hordein peptide (QPFPQPEQPFPW) and a rye-derived secalin peptide (QPFPQPQQPIPQ) were proposed to be toxic in CD, as they yielded positive responses when assessed with peripheral blood T-cell clones derived from individuals with CD. We sought to assess the immunogenicity of the candidate peptides using gluten-sensitive T-cell lines obtained from CD small intestinal biopsies. We also sought to investigate the potential cross-reactivity of wheat gluten-sensitive T-cell lines with peptic-tryptic digested barley hordein (PTH) and rye secalin (PTS). Synthesised candidate peptides were deamidated with tissue transglutaminase (tTG). Gluten-sensitive T-cell lines were generated by culturing small intestinal biopsies from CD patients with peptic-tryptic gluten (PTG), PTH or PTS, along with autologous PBMCs for antigen presentation. The stimulation indices were determined by measuring the relative cellular proliferation via incorporation of 3 H-thymidine. The majority of T-cell lines reacted to the peptides studied. There was also cross-reactivity between wheat gluten-sensitive T-cell lines and the hordein, gliadin and secalin peptides. PTH, PTS, barley hordein and rye secalin-derived CD antigen-sensitive T-cell lines showed positive stimulation with PTG. ω-gliadin/C-hordein peptide and rye-derived peptide are immunogenic to gluten-sensitive T-cell lines and potentially present in wheat, rye and barley. Additional CD toxic peptides may be shared.
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Affiliation(s)
- Widya A Wahab
- Department of Biotechnology, Kulliyyah of Science, International Islamic University Malaysia (IIUM), Kuantan, Malaysia
| | - Tanja Šuligoj
- Division of Diabetes and Nutritional Sciences, Department of Gastroenterology, King's College London, Rayne Institute, St. Thomas' Hospital, London, UK
| | - Julia Ellis
- Division of Diabetes and Nutritional Sciences, Department of Gastroenterology, King's College London, Rayne Institute, St. Thomas' Hospital, London, UK
| | - Beatriz Côrtez-Real
- Division of Diabetes and Nutritional Sciences, Department of Gastroenterology, King's College London, Rayne Institute, St. Thomas' Hospital, London, UK
| | - Paul J Ciclitira
- Division of Diabetes and Nutritional Sciences, Department of Gastroenterology, King's College London, Rayne Institute, St. Thomas' Hospital, London, UK.
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46
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Celiac disease: understanding the gluten-free diet. Eur J Nutr 2016; 56:449-459. [DOI: 10.1007/s00394-016-1238-5] [Citation(s) in RCA: 126] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2015] [Accepted: 05/27/2016] [Indexed: 12/15/2022]
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Singh AK, Singh R, Subramani R, Kumar R, Wankhede DP. Molecular Approaches to Understand Nutritional Potential of Coarse Cereals. Curr Genomics 2016; 17:177-92. [PMID: 27252585 PMCID: PMC4869005 DOI: 10.2174/1389202917666160202215308] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2015] [Revised: 06/26/2015] [Accepted: 06/29/2015] [Indexed: 01/01/2023] Open
Abstract
Coarse grains are important group of crops that constitutes staple food for large population residing primarily in the arid and semi-arid regions of the world. Coarse grains are designated as nutri-cereals as they are rich in essential amino acids, minerals and vitamins. In spite of having several nutritional virtues in coarse grain as mentioned above, there is still scope for improvement in quality parameters such as cooking qualities, modulation of nutritional constituents and reduction or elimination of anti-nutritional factors. Besides its use in traditional cooking, coarse grains have been used mainly in the weaning food preparation and other malted food production. Improvement in quality parameters will certainly increase consumer's preference for coarse grains and increase their demand. The overall genetic gain in quality traits of economic importance in the cultivated varieties will enhance their industrial value and simultaneously increase income of farmers growing these varieties. The urgent step for improvement of quality traits in coarse grains requires a detailed understanding of molecular mechanisms responsible for varied level of different nutritional contents in different genotypes of these crops. In this review we have discussed the progresses made in understanding of coarse grain biology with various omics tool coupled with modern breeding approaches and the current status with regard to our effort towards dissecting traits related to improvement of quality and nutritional constituents of grains.
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Affiliation(s)
- Amit Kumar Singh
- Division of Genomic Resources, ICAR- National Bureau of Plant Genetic Resources, New Delhi, India
| | - Rakesh Singh
- Division of Genomic Resources, ICAR- National Bureau of Plant Genetic Resources, New Delhi, India
| | - Rajkumar Subramani
- Division of Genomic Resources, ICAR- National Bureau of Plant Genetic Resources, New Delhi, India
| | - Rajesh Kumar
- Division of Genomic Resources, ICAR- National Bureau of Plant Genetic Resources, New Delhi, India
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Comino I, Bernardo D, Bancel E, de Lourdes Moreno M, Sánchez B, Barro F, Šuligoj T, Ciclitira PJ, Cebolla Á, Knight SC, Branlard G, Sousa C. Identification and molecular characterization of oat peptides implicated on coeliac immune response. Food Nutr Res 2016; 60:30324. [PMID: 26853779 PMCID: PMC4744869 DOI: 10.3402/fnr.v60.30324] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2015] [Revised: 12/06/2015] [Accepted: 12/07/2015] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Oats provide important nutritional and pharmacological properties, although their safety in coeliac patients remains controversial. Previous studies have confirmed that the reactivity of the anti-33-mer monoclonal antibody with different oat varieties is proportional to the immune responses in terms of T-cell proliferation. Although the impact of these varieties on the adaptive response has been studied, the role of the dendritic cells (DC) is still poorly understood. The aim of this study is to characterize different oat fractions and to study their effect on DC from coeliac patients. METHODS AND RESULTS Protein fractions were isolated from oat grains and analyzed by SDS-PAGE. Several proteins were characterized in the prolamin fraction using immunological and proteomic tools, and by Nano-LC-MS/MS. These proteins, analogous to α- and γ-gliadin-like, showed reactive sequences to anti-33-mer antibody suggesting their immunogenic potential. That was further confirmed as some of the newly identified oat peptides had a differential stimulatory capacity on circulating DC from coeliac patients compared with healthy controls. CONCLUSIONS This is the first time, to our knowledge, where newly identified oat peptides have been shown to elicit a differential stimulatory capacity on circulating DC obtained from coeliac patients, potentially identifying immunogenic properties of these oat peptides.
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Affiliation(s)
- Isabel Comino
- Departamento de Microbiología y Parasitología, Facultad de Farmacia, Universidad de Sevilla, Sevilla, Spain
| | - David Bernardo
- Gastroenterology Unit, Antigen Presentation Research Group, Imperial College London & St Mark's Hospital, Harrow, United Kingdom.,Hospital Universitario de La Princesa and Instituto de Investigación Sanitaria Princesa (IIS-IP), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | | | - María de Lourdes Moreno
- Departamento de Microbiología y Parasitología, Facultad de Farmacia, Universidad de Sevilla, Sevilla, Spain
| | - Borja Sánchez
- Nutrition and Bromatology Group, Department of Analytical and Food Chemistry, Food Science and Technology Faculty, University of Vigo-Ourense Campus, Ourense, Spain
| | | | - Tanja Šuligoj
- Division of Diabetes and Nutritional Sciences, King's College London, Gastroenterology, The Rayne Institute, St Thomas' Hospital, London, United Kingdom
| | - Paul J Ciclitira
- Division of Diabetes and Nutritional Sciences, King's College London, Gastroenterology, The Rayne Institute, St Thomas' Hospital, London, United Kingdom
| | | | - Stella C Knight
- Gastroenterology Unit, Antigen Presentation Research Group, Imperial College London & St Mark's Hospital, Harrow, United Kingdom
| | | | - Carolina Sousa
- Departamento de Microbiología y Parasitología, Facultad de Farmacia, Universidad de Sevilla, Sevilla, Spain;
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Panda R, Fiedler KL, Cho CY, Cheng R, Stutts WL, Jackson LS, Garber EAE. Effects of a Proline Endopeptidase on the Detection and Quantitation of Gluten by Antibody-Based Methods during the Fermentation of a Model Sorghum Beer. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2015; 63:10525-10535. [PMID: 26548701 DOI: 10.1021/acs.jafc.5b04205] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/05/2023]
Abstract
The effectiveness of a proline endopeptidase (PEP) in hydrolyzing gluten and its putative immunopathogenic sequences was examined using antibody-based methods and mass spectrometry (MS). Based on the results of the antibody-based methods, fermentation of wheat gluten containing sorghum beer resulted in a reduction in the detectable gluten concentration. The addition of PEP further reduced the gluten concentration. Only one sandwich ELISA was able to detect the apparent low levels of gluten present in the beers. A competitive ELISA using a pepsin-trypsin hydrolysate calibrant was unreliable because the peptide profiles of the beers were inconsistent with that of the hydrolysate calibrant. Analysis by MS indicated that PEP enhanced the loss of a fragment of an immunopathogenic 33-mer peptide in the beer. However, Western blot results indicated partial resistance of the high molecular weight (HMW) glutenins to the action of PEP, questioning the ability of PEP in digesting all immunopathogenic sequences present in gluten.
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Affiliation(s)
- Rakhi Panda
- Division of Bioanalytical Chemistry, Office of Regulatory Science, Center for Food Safety and Applied Nutrition (CFSAN), FDA , College Park, Maryland 20740, United States
| | - Katherine L Fiedler
- Division of Analytical Chemistry, Office of Regulatory Science, Center for Food Safety and Applied Nutrition (CFSAN), FDA , College Park, Maryland 20740, United States
| | - Chung Y Cho
- Division of Bioanalytical Chemistry, Office of Regulatory Science, Center for Food Safety and Applied Nutrition (CFSAN), FDA , College Park, Maryland 20740, United States
| | - Raymond Cheng
- Joint Institute for Food Safety and Applied Nutrition (JIFSAN), University of Maryland , College Park, Maryland 20740, United States
| | - Whitney L Stutts
- Division of Analytical Chemistry, Office of Regulatory Science, Center for Food Safety and Applied Nutrition (CFSAN), FDA , College Park, Maryland 20740, United States
| | - Lauren S Jackson
- Division of Food Processing Science and Technology, Office of Food Safety, CFSAN, FDA , Bedford Park, Illinois 60501, United States
| | - Eric A E Garber
- Division of Bioanalytical Chemistry, Office of Regulatory Science, Center for Food Safety and Applied Nutrition (CFSAN), FDA , College Park, Maryland 20740, United States
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50
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Comino I, Moreno MDL, Sousa C. Role of oats in celiac disease. World J Gastroenterol 2015; 21:11825-11831. [PMID: 26557006 PMCID: PMC4631980 DOI: 10.3748/wjg.v21.i41.11825] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2015] [Revised: 09/02/2015] [Accepted: 09/15/2015] [Indexed: 02/06/2023] Open
Abstract
A gluten-free diet is currently the only effective means of treating individuals with celiac disease. Such a diet enables celiac patients to control their symptoms and avoid various complications associated with this condition. However, while the quality of gluten-free foods has significantly improved during recent decades, maintenance of a gluten-free diet does not necessarily ensure adequate nutritional intake. Because oats are an important source of proteins, lipids, vitamins, minerals, and fibre, their inclusion in a gluten-free diet might improve the nutritional status of a celiac patient. Although oats are included in the list of gluten-free ingredients specified in European regulations, their safety when consumed by celiac patients remains debatable. Some studies claim that pure oats are safe for most celiac people, and contamination with other cereal sources is the main problem facing people with this disease. However, it is necessary to consider that oats include many varieties, containing various amino acid sequences and showing different immunoreactivities associated with toxic prolamins. As a result, several studies have shown that the immunogenicity of oats varies depending on the cultivar consumed. Thus, it is essential to thoroughly study the variety of oats used in a food ingredient before including it in a gluten-free diet.
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