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Carroccio A, Rostami K, Fasano A, Giuliano A, Catassi C. Nonceliac Wheat Sensitivity. Gastrointest Endosc Clin N Am 2025. [DOI: 10.1016/j.giec.2025.02.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/01/2025]
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Manza F, Lungaro L, Costanzini A, Caputo F, Carroccio A, Mansueto P, Seidita A, Raju SA, Volta U, De Giorgio R, Sanders DS, Caio G. Non-Celiac Gluten/Wheat Sensitivity-State of the Art: A Five-Year Narrative Review. Nutrients 2025; 17:220. [PMID: 39861350 PMCID: PMC11767908 DOI: 10.3390/nu17020220] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2024] [Revised: 12/31/2024] [Accepted: 01/03/2025] [Indexed: 01/27/2025] Open
Abstract
Background: Non-celiac gluten/wheat sensitivity (NCGWS) is a syndrome for which pathogenesis and management remain debated. It is described as a condition characterized by gastrointestinal and extra-intestinal symptoms rapidly occurring after gluten ingestion in subjects who have had celiac disease or wheat allergy excluded. To date, the diagnosis of NCGWS is challenging as no universally recognized biomarkers have been yet identified, nor has a predisposing genetic profile been described. However, the research is moving fast, and new data regarding pathogenic pathways, patients' classification, potential candidate biomarkers, and dietary interventions are emerging. Methods: This literature review aims to address the state of the art and summarize the latest updates in this field from 2019 to date. Results and Conclusions: Clinical studies regarding NCGWS in the last five years are reported to shed light on this complex condition and to guide specialists towards a more in-depth, prompt, and objective diagnosis.
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Affiliation(s)
- Francesca Manza
- Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy; (F.M.); (A.C.); (F.C.); (R.D.G.); (G.C.)
- Academic Unit of Gastroenterology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield S5 7AT, UK; (S.A.R.); (D.S.S.)
| | - Lisa Lungaro
- Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy; (F.M.); (A.C.); (F.C.); (R.D.G.); (G.C.)
| | - Anna Costanzini
- Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy; (F.M.); (A.C.); (F.C.); (R.D.G.); (G.C.)
| | - Fabio Caputo
- Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy; (F.M.); (A.C.); (F.C.); (R.D.G.); (G.C.)
| | - Antonio Carroccio
- Unit of Internal Medicine, “V. Cervello” Hospital, Ospedali Riuniti “Villa Sofia-Cervello”, 90146 Palermo, Italy; (A.C.); (A.S.)
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy;
| | - Pasquale Mansueto
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy;
| | - Aurelio Seidita
- Unit of Internal Medicine, “V. Cervello” Hospital, Ospedali Riuniti “Villa Sofia-Cervello”, 90146 Palermo, Italy; (A.C.); (A.S.)
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy;
- Institute for Biomedical Research and Innovation (IRIB), National Research Council (CNR), 90146 Palermo, Italy
| | - Suneil A. Raju
- Academic Unit of Gastroenterology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield S5 7AT, UK; (S.A.R.); (D.S.S.)
| | - Umberto Volta
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy;
| | - Roberto De Giorgio
- Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy; (F.M.); (A.C.); (F.C.); (R.D.G.); (G.C.)
| | - David S. Sanders
- Academic Unit of Gastroenterology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield S5 7AT, UK; (S.A.R.); (D.S.S.)
| | - Giacomo Caio
- Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy; (F.M.); (A.C.); (F.C.); (R.D.G.); (G.C.)
- Mucosal Immunology and Biology Research Center, Massachusetts General Hospital—Harvard Medical School, Boston, MA 02114, USA
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Catassi G, Catassi C. An overview of progress in establishing a diagnostic tool for non-celiac gluten sensitivity. Expert Rev Mol Diagn 2025; 25:59-66. [PMID: 39863935 DOI: 10.1080/14737159.2025.2458469] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2024] [Revised: 01/17/2025] [Accepted: 01/22/2025] [Indexed: 01/27/2025]
Abstract
INTRODUCTION Non-Celiac Gluten Sensitivity (NCGS) is a common disorder characterized by symptoms resembling those of irritable bowel syndrome. In recent years there has been progress in the understanding of the pathogenic pathways and data suggest that NCGS has a distinct immunological profile that differs from celiac disease (CeD). This has fostered the search for a specific biomarker of NCGS. AREAS COVERED In this review we will firstly update on pioneer NCGS diagnostic tools, particularly the gluten challenge, serum IgG class antigliadin antibodies, and certain histological characteristics seen at the small intestinal biopsy. Then we will examine the most recent research on potential biomarkers of NCGS, specifically focusing on markers of damage to enterocytes, of translocation of bacteria from the gut into the bloodstream, intestinal permeability, and inflammation. EXPERT OPINION So far, no specific biomarker of NCGS has been detected. The diagnosis of NCGS still relies on clinical criteria. A gluten challenge may be useful for diagnostic purposes, however a strong nocebo effect limits the efficacy of this procedure. Additional investigation is necessary to identify biomarkers for NCGS, that may be useful to investigate the epidemiology, clinical spectrum, and natural history of this common disorder.
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Affiliation(s)
- Giulia Catassi
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Carlo Catassi
- Department of Pediatrics, Polytechnic University of Marche, Ancona, Italy
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Whelan K, Ford AC, Burton-Murray H, Staudacher HM. Dietary management of irritable bowel syndrome: considerations, challenges, and solutions. Lancet Gastroenterol Hepatol 2024; 9:1147-1161. [PMID: 39521003 DOI: 10.1016/s2468-1253(24)00238-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Revised: 07/19/2024] [Accepted: 07/23/2024] [Indexed: 11/16/2024]
Abstract
Diet is a cornerstone in the management of irritable bowel syndrome (IBS). There is evidence of efficacy across the spectrum of dietary management strategies, including some supplements (eg, specific fibres), foods, and whole diets (eg, a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols [known as the low-FODMAP diet]). Whole-diet interventions, in particular those that restrict intake, can be challenging to deliver effectively and safely. Factors to consider include patient demographics, food cost and availability, and the acceptability of dietary management and its impact on food-related quality of life. There is concern regarding a potential role of restrictive whole-diet interventions in eating disorder risk. Optimal approaches to delivering dietary management in the health-care setting are unclear. The aim of this Review is to summarise the clinical evidence for the dietary management of IBS; to discuss the challenges, burdens, and risks of dietary management; and to propose how these challenges, burdens, and risks should be mitigated and minimised in clinical practice.
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Affiliation(s)
- Kevin Whelan
- Department of Nutritional Sciences, King's College London, London, UK.
| | - Alexander C Ford
- Leeds Gastroenterology Institute, St James's University Hospital, Leeds, UK; Leeds Institute of Medical Research, University of Leeds, Leeds, UK
| | - Helen Burton-Murray
- Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA
| | - Heidi M Staudacher
- Food and Mood Centre, Institute for Mental and Physical Health and Clinical Translation, Deakin University, Geelong, VIC, Australia
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Herfindal AM, Nilsen M, Aspholm TE, Schultz GIG, Valeur J, Rudi K, Thoresen M, Lundin KEA, Henriksen C, Bøhn SK. Effects of fructan and gluten on gut microbiota in individuals with self-reported non-celiac gluten/wheat sensitivity-a randomised controlled crossover trial. BMC Med 2024; 22:358. [PMID: 39227818 PMCID: PMC11373345 DOI: 10.1186/s12916-024-03562-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Accepted: 08/14/2024] [Indexed: 09/05/2024] Open
Abstract
BACKGROUND Individuals with non-celiac gluten/wheat sensitivity (NCGWS) experience improvement in gastrointestinal symptoms following a gluten-free diet. Although previous results have indicated that fructo-oligosaccharides (FOS), a type of short-chain fructans, were more likely to induce symptoms than gluten in self-reported NCGWS patients, the underlying mechanisms are unresolved. METHODS Our main objective was therefore to investigate whether FOS-fructans and gluten affect the composition and diversity of the faecal microbiota (16S rRNA gene sequencing), faecal metabolites of microbial fermentation (short-chain fatty acids [SCFA]; gas chromatography with flame ionization detector), and a faecal biomarker of gut inflammation (neutrophil gelatinase-associated lipocalin, also known as lipocalin 2, NGAL/LCN2; ELISA). In the randomised double-blind placebo-controlled crossover study, 59 participants with self-reported NCGWS underwent three different 7-day diet challenges with gluten (5.7 g/day), FOS-fructans (2.1 g/day), and placebo separately (three periods, six challenge sequences). RESULTS The relative abundances of certain bacterial taxa were affected differently by the diet challenges. After the FOS-fructan challenge, Fusicatenibacter increased, while Eubacterium (E.) coprostanoligenes group, Anaerotruncus, and unknown Ruminococcaceae genera decreased. The gluten challenge was primarily characterized by increased abundance of Eubacterium xylanophilum group. However, no differences were found for bacterial diversity (α-diversity), overall bacterial community structure (β-diversity), faecal metabolites (SCFA), or NGAL/LCN2. Furthermore, gastrointestinal symptoms in response to FOS-fructans were generally not linked to substantial shifts in the gut bacterial community. However, the reduction in E. coprostanoligenes group following the FOS-fructan challenge was associated with increased gastrointestinal pain. Finally, correlation analysis revealed that changes in gastrointestinal symptoms following the FOS-fructan and gluten challenges were linked to varying bacterial abundances at baseline. CONCLUSIONS In conclusion, while FOS-fructans induced more gastrointestinal symptoms than gluten in the NCGWS patients, we did not find that substantial shifts in the composition nor function of the faecal microbiota could explain these differences in the current study. However, our results indicate that individual variations in baseline bacterial composition/function may influence the gastrointestinal symptom response to both FOS-fructans and gluten. Additionally, the change in E. coprostanoligenes group, which was associated with increased symptoms, implies that attention should be given to these bacteria in future trials investigating the impact of dietary treatments on gastrointestinal symptoms. TRIAL REGISTRATION Clinicaltrials.gov as NCT02464150.
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Affiliation(s)
- Anne Mari Herfindal
- Faculty of Chemistry, Biotechnology and Food Sciences, Norwegian University of Life Sciences, P. O. Box 5003, N-1432, Ås, Norway
| | - Morten Nilsen
- Faculty of Chemistry, Biotechnology and Food Sciences, Norwegian University of Life Sciences, P. O. Box 5003, N-1432, Ås, Norway
| | - Trude E Aspholm
- Faculty of Chemistry, Biotechnology and Food Sciences, Norwegian University of Life Sciences, P. O. Box 5003, N-1432, Ås, Norway
| | | | - Jørgen Valeur
- Unger-Vetlesen Institute, Lovisenberg Diaconal Hospital, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Knut Rudi
- Faculty of Chemistry, Biotechnology and Food Sciences, Norwegian University of Life Sciences, P. O. Box 5003, N-1432, Ås, Norway
| | - Magne Thoresen
- Department of Biostatistics, Faculty of Medicine, University of Oslo, Oslo, Norway
| | - Knut E A Lundin
- Disease Research Centre, Norwegian Coeliac, University of Oslo, Oslo, Norway
- Department of Gastroenterology, Oslo University Hospital Rikshospitalet, Oslo, Norway
| | - Christine Henriksen
- Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
| | - Siv K Bøhn
- Faculty of Chemistry, Biotechnology and Food Sciences, Norwegian University of Life Sciences, P. O. Box 5003, N-1432, Ås, Norway.
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Wall E, Semrad CE. Celiac Disease, Gluten Sensitivity, and Diet Management. Curr Gastroenterol Rep 2024; 26:191-199. [PMID: 38865028 DOI: 10.1007/s11894-024-00931-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/02/2024] [Indexed: 06/13/2024]
Abstract
PURPOSE OF REVIEW Celiac disease is a common chronic inflammatory condition of the small bowel triggered by gluten in wheat, rye and barley in the diet. Non-celiac gluten sensitivity presents with symptoms similar to celiac disease with the ingestion of gluten or other components of wheat. In this article, we review challenges presented by a gluten free diet for the treatment of both disorders. RECENT FINDINGS Wheat is ubiquitous in the diet and medications/products. A registered dietitian is mandatory for patient education on the gluten free diet. Naturally gluten free foods provide a healthy diet for those with celiac disease. Whole grains labelled gluten free, including oats, are encouraged in the diet as refined grains may be deficient in fiber, protein, and micronutrients, particularly folate. Gluten contamination is the most common cause of persistent symptoms in celiac disease though shared equipment of food preparation may not be as large a problem as suspected. Most with celiac disease on a gluten free diet will fully recover and gain weight that poses a problem for those overweight to start. The gluten free diet may have a negative impact on quality of life for both celiac patients and their families. Those with hypervigilance of the gluten free diet and avoidance of dining out have the lowest quality of life. The gluten free diet is currently the only effective treatment for celiac disease. A registered dietitian is needed to educate patients on the complexity of the gluten free diet with a goal of healthy eating, maintaining a healthy weight, and avoiding disordered eating or diet hypervigilance; key to a good quality of life.
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Affiliation(s)
- Elizabeth Wall
- Clinical Nutrition, University of Chicago Medicine, Chicago, IL, USA
| | - Carol E Semrad
- Section of Gastroenterology, Hepatology and Nutrition, University of Chicago Medicine, Chicago, IL, USA.
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Seidita A, Giuliano A, Soresi M, Chiavetta M, Nardi E, Mogavero G, Giannone G, Carroccio A, Mansueto P. Fecal calprotectin levels in patients with non-celiac wheat sensitivity: a proof of concept. Intern Emerg Med 2024; 19:1255-1266. [PMID: 38609737 PMCID: PMC11364563 DOI: 10.1007/s11739-024-03595-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Accepted: 03/23/2024] [Indexed: 04/14/2024]
Abstract
Some data suggest the existence of intestinal inflammation in patients with non-celiac wheat sensitivity (NCWS). We aimed to verify whether fecal calprotectin (FCP), a marker of intestinal inflammation, could be used to confirm this inflammatory status and to test its diagnostic performance in differentiating NCWS from irritable bowel syndrome/functional dyspepsia (IBS/FD). We conducted a multicenter study, comparing NCWS patients, diagnosed by a double-blind placebo-controlled wheat challenge, with IBS/FD subjects. In the retrospective phase, FCP values were analyzed to define the prevalence of its positivity and its role as a NCWS diagnostic biomarker. In the prospective phase we tested the effects of a strict 6-month wheat-free diet (WFD) on FCP values. 31.3% (n = 63/201) of NCWS patients had above normal FCP values (NCWS FCP +), whereas all IBS/FD patients proved negative (P = 0.0001). FCP using a cut-off value > 41 µg/g showed a 58.6% sensitivity and a 98.0% specificity (AUC 0.755, 95% C.I. 0.702-0.837) in distinguishing NCWS from IBS/FD patients. Of the 63 NCWS FCP+, 65.1% had negative FCP values after ≥ 6 months of WFD, with a significant reduction in FCP values (P < 0.0001). All NCWS FCP- subjects still preserved negative FCP values after ≥ 6 months of WFD. Our study showed that FCP can be a useful but supplementary diagnostic marker for differentiating between NCWS and IBS/FD. Strict WFD adherence reduced FCP values, normalizing them in 65.1% of NCWS FCP + subjects. These data suggest the existence of two NCWS subgroups: NCWS FCP + characterized by a probable predominantly inflammatory/immunologic pattern and NCWS FCP- featuring non-immuno-mediated etiopathogenetic mechanisms. (Registration number NCT01762579).
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Affiliation(s)
- Aurelio Seidita
- Unit of Internal Medicine, "V. Cervello" Hospital, Ospedali Riuniti "Villa Sofia-Cervello", Via Trabucco, 180, 90146, Palermo, Italy
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy
- Institute for Biomedical Research and Innovation (IRIB), National Research Council (CNR), Palermo, Italy
| | - Alessandra Giuliano
- Unit of Internal Medicine, "V. Cervello" Hospital, Ospedali Riuniti "Villa Sofia-Cervello", Via Trabucco, 180, 90146, Palermo, Italy
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy
| | - Maurizio Soresi
- Unit of Internal Medicine, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy
| | - Marta Chiavetta
- Unit of Internal Medicine, "V. Cervello" Hospital, Ospedali Riuniti "Villa Sofia-Cervello", Via Trabucco, 180, 90146, Palermo, Italy
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy
| | - Emilio Nardi
- Unit of Internal Medicine II, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy
| | - Giuseppe Mogavero
- Unit of Gastroenterology, "V. Cervello" Hospital, Ospedali Riuniti "Villa Sofia-Cervello", Palermo, Italy
| | - Giulio Giannone
- Pathology Unit, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy
| | - Antonio Carroccio
- Unit of Internal Medicine, "V. Cervello" Hospital, Ospedali Riuniti "Villa Sofia-Cervello", Via Trabucco, 180, 90146, Palermo, Italy.
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy.
| | - Pasquale Mansueto
- Unit of Internal Medicine, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy
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van Haaps AP, Brouns F, Schreurs AM, Keszthelyi D, Maas JW, Mijatovic V. A gluten-free diet for endometriosis patients lacks evidence to recommend it. AJOG GLOBAL REPORTS 2024; 4:100369. [PMID: 39040659 PMCID: PMC11262165 DOI: 10.1016/j.xagr.2024.100369] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/24/2024] Open
Abstract
Endometriosis is an estrogen-dependent chronic disease characterized by the presence of endometriumlike tissue outside the uterus and is often associated with symptoms, such as dysmenorrhea, dysuria, dyschezia, chronic pelvic pain, and infertility. Moreover, women diagnosed with endometriosis can report gastrointestinal symptoms, including bloating, constipation or diarrhea, and abdominal cramping, which can be associated with irritable bowel syndrome and can result in the misdiagnosis of endometriosis as irritable bowel syndrome at first. Treatment usually involves hormonal therapy, pain management, surgery, and/or assisted reproductive techniques in case of infertility. Nonetheless, these treatment methods can be insufficient for alleviating symptoms or can have unacceptable side effects, leading to noncompliance. Therefore, women often apply self-management strategies, including dietary interventions. One of the diets frequently suggested as a tool to manage endometriosis-related symptoms on social media and patient forums is a gluten-free diet. Although a gluten-free diet has been proven effective in managing nonceliac wheat sensitivity or celiac disease, its effectiveness in endometriosis remains uncertain. The Nurses' Health Study II found it unlikely that gluten intake was a strong factor in endometriosis etiology and symptomatology. To the best of our knowledge, the most frequently cited and sole published intervention study on the efficacy of a gluten-free diet for endometriosis has several important limiting factors, including the absence of a control group. In addition, gluten consumption is highly susceptible to a placebo effect and a nocebo effect, where women might experience symptom relief after eliminating gluten and return of symptoms after they consume gluten again, solely because they believe that gluten is bad for them. Despite the inverse association between body mass index and endometriosis and between a gluten-free diet and increased body mass index, this is an association, and no causality was proven. In addition, other factors should be taken into consideration. Of note, a gluten-free diet is expensive, has limited availability, and has a significant effect on quality of life. Moreover, without proper dietary guidance, it may adversely affect the gastrointestinal microbiome. Therefore, scientifically substantiated advice regarding the use of a gluten-free diet for endometriosis-related symptoms is currently not available, and a gluten-free diet should be discouraged unless there is an additional diagnosis of nonceliac wheat sensitivity or celiac disease.
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Affiliation(s)
- Annelotte P. van Haaps
- Department of Reproductive Medicine and Endometriosis Center, Amsterdam University Medical Center, Amsterdam, The Netherlands (van Haaps, Schreurs, and Mijatovic)
- Amsterdam Reproduction and Development Research Institute, Amsterdam, The Netherlands (van Haaps, Schreurs, and Mijatovic)
| | - Fred Brouns
- Department of Human Biology, School for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands (Brouns)
| | - Anneke M.F. Schreurs
- Department of Reproductive Medicine and Endometriosis Center, Amsterdam University Medical Center, Amsterdam, The Netherlands (van Haaps, Schreurs, and Mijatovic)
- Amsterdam Reproduction and Development Research Institute, Amsterdam, The Netherlands (van Haaps, Schreurs, and Mijatovic)
| | - Daniel Keszthelyi
- Department of Gastroenterology and Hepatology, Nutrition and Translational Research in Metabolism Research Institute, Maastricht University Medical Center, Maastricht University, Maastricht, The Netherlands (Keszthelyi)
| | - Jacques W.M. Maas
- GROW Research Institute for Oncology and Reproduction, Maastricht University, Maastricht, The Netherlands (Maas)
- Department of Obstetrics and Gynaecology, Maastricht University Medical Center, Maastricht, The Netherlands (Maas)
| | - Velja Mijatovic
- Department of Reproductive Medicine and Endometriosis Center, Amsterdam University Medical Center, Amsterdam, The Netherlands (van Haaps, Schreurs, and Mijatovic)
- Amsterdam Reproduction and Development Research Institute, Amsterdam, The Netherlands (van Haaps, Schreurs, and Mijatovic)
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Martín-Cardona A, Carrasco A, Arau B, Vidal J, Tristán E, Ferrer C, Gonzalez-Puglia G, Pallarès N, Tebé C, Farrais S, Núñez C, Fernández-Bañares F, Esteve M. γδ+ T-Cells Is a Useful Biomarker for the Differential Diagnosis between Celiac Disease and Non-Celiac Gluten Sensitivity in Patients under Gluten Free Diet. Nutrients 2024; 16:2294. [PMID: 39064736 PMCID: PMC11279444 DOI: 10.3390/nu16142294] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Revised: 07/09/2024] [Accepted: 07/10/2024] [Indexed: 07/28/2024] Open
Abstract
BACKGROUND The differential diagnosis between patients with celiac disease (CD) and non-celiac gluten sensitivity (NCGS) is difficult when a gluten-free diet (GFD) has been initiated before the diagnostic work-up. Isolated increases in TCRγδ+ and celiac lymphogram (increased TCRγδ+ plus decreased CD3-) may enable differential diagnosis in this challenging clinical setting. This study evaluated: (1) the accuracy of %TCRγδ+ and celiac lymphogram for diagnosing CD before and after GFD and for differentiation with NCGS; (2) TCRγδ+ kinetics at baseline and after starting GFD in both CD and NCGS. METHODS The inclusion criteria were patients with CD (n = 104), NCGS (n = 37), and healthy volunteers (n = 18). An intestinal biopsy for intraepithelial lymphogram by flow cytometry was performed at baseline and after GFD. The optimal cutoff for CD diagnostic accuracy was established by maximizing the Youden index and via logistic regression. RESULTS %TCRγδ+ showed better diagnostic accuracy than celiac lymphogram for identifying CD before and after GFD initiation. With a cutoff > 13.31, the accuracy for diagnosing CD in patients under GFD was 0.88 [0.80-0.93], whereas the accuracy for diagnosing NCGS (%TCRγδ+ ≤ 13.31) was 0.84 [0.76-0.89]. The percentage of TCRγδ+ cells showed differential kinetics between CD (baseline 22.7% [IQR, 16.4-33.6] vs. after GFD 26.4% [IQR, 17.8-36.8]; p = 0.026) and NCGS (baseline 9.4% [IQR, 4.1-14.6] vs. after GFD 6.4% [IQR, 3.2-11]; p = 0.022). CONCLUSION TCRγδ+ T cell assessment accurately diagnoses CD before and after a GFD. Increased TCRγδ+ was maintained in the long term after GFD in CD but not in NCGS. Altogether, this suggests the potential usefulness of this marker for the differential diagnosis of these two entities in patients on a GFD.
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Affiliation(s)
- Albert Martín-Cardona
- Gastroenterology Department, Hospital Universitari Mútua Terrassa, University of Barcelona, 08221 Terrassa, Spain; (A.M.-C.); (A.C.); (B.A.); (E.T.); (G.G.-P.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Anna Carrasco
- Gastroenterology Department, Hospital Universitari Mútua Terrassa, University of Barcelona, 08221 Terrassa, Spain; (A.M.-C.); (A.C.); (B.A.); (E.T.); (G.G.-P.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Beatriz Arau
- Gastroenterology Department, Hospital Universitari Mútua Terrassa, University of Barcelona, 08221 Terrassa, Spain; (A.M.-C.); (A.C.); (B.A.); (E.T.); (G.G.-P.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Judith Vidal
- Department of Flow Cytometry, Catlab, 08232 Viladecavalls, Spain;
| | - Eva Tristán
- Gastroenterology Department, Hospital Universitari Mútua Terrassa, University of Barcelona, 08221 Terrassa, Spain; (A.M.-C.); (A.C.); (B.A.); (E.T.); (G.G.-P.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Carme Ferrer
- Pathology Department, Hospital Universitari Mútua Terrassa, University of Barcelona, 08221 Terrassa, Spain;
| | - Gerardo Gonzalez-Puglia
- Gastroenterology Department, Hospital Universitari Mútua Terrassa, University of Barcelona, 08221 Terrassa, Spain; (A.M.-C.); (A.C.); (B.A.); (E.T.); (G.G.-P.)
| | - Natàlia Pallarès
- Biostatistics Support and Research Unit, Germans Trias i Pujol Research Institute and Hospital (IGTP), 08916 Badalona, Spain; (N.P.); (C.T.)
| | - Cristian Tebé
- Biostatistics Support and Research Unit, Germans Trias i Pujol Research Institute and Hospital (IGTP), 08916 Badalona, Spain; (N.P.); (C.T.)
| | - Sergio Farrais
- Gastroenterology Department, Hospital Universitario Fundación Jiménez Díaz, 28040 Madrid, Spain;
| | - Concepción Núñez
- Laboratorio de Investigación en Genética de Enfermedades Complejas, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid, Spain;
| | - Fernando Fernández-Bañares
- Gastroenterology Department, Hospital Universitari Mútua Terrassa, University of Barcelona, 08221 Terrassa, Spain; (A.M.-C.); (A.C.); (B.A.); (E.T.); (G.G.-P.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Maria Esteve
- Gastroenterology Department, Hospital Universitari Mútua Terrassa, University of Barcelona, 08221 Terrassa, Spain; (A.M.-C.); (A.C.); (B.A.); (E.T.); (G.G.-P.)
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain
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10
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Mousavi Khaneghah A, Mostashari P. Decoding food reactions: a detailed exploration of food allergies vs. intolerances and sensitivities. Crit Rev Food Sci Nutr 2024; 65:2669-2713. [PMID: 38747015 DOI: 10.1080/10408398.2024.2349740] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
The food matrix is a complex system encompassing all constituent elements in food production. It influences the digestibility of these elements through direct interactions and affects the digestive environment. Furthermore, the gastrointestinal system possesses precise mechanisms that efficiently process dietary components into essential nutrients, effectively preventing the onset of abnormal immune responses or dysfunctional host reactions in most instances. However, the incidence of adverse food reactions is constantly increasing, and evidence indicates that this process is environmental. Adverse reactions can be categorized as toxic or nontoxic. Toxic reactions are dose-dependent and can result from natural compounds, processing-induced substances, or contaminants. Nontoxic reactions like food intolerance and hypersensitivity depend on individual susceptibility and evoke specific pathological and physiological responses. This review aims to elucidate the mechanisms underlying the occurrence of immune- (food allergies and sensitivities) and non-immune-mediated (food intolerance) reactions, emphasizing the fundamental distinctions between these two categories. Enhanced comprehension and distinction of these mechanisms will significantly contribute to advancing preventive and therapeutic approaches and establishing guidelines for food labeling concerning immune-mediated reactions.
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Affiliation(s)
| | - Parisa Mostashari
- Department of Food Science and Technology, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Department of Food Science and Technology, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
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11
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Abbasi A, Bazzaz S, A. Ibrahim S, Hekmatdoost A, Hosseini H, Sabahi S, Sheykhsaran E, Rahbar Saadat Y, Asghari Ozma M, Lahouty M. A Critical Review on the Gluten-Induced Enteropathy/Celiac Disease: Gluten-Targeted Dietary and Non-Dietary Therapeutic Approaches. FOOD REVIEWS INTERNATIONAL 2024; 40:883-923. [DOI: 10.1080/87559129.2023.2202405] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Affiliation(s)
- Amin Abbasi
- Student Research Committee, Department of Food Science and Technology, National Nutrition and Food Technology Research Institute, Faculty of Nutrition Science and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sara Bazzaz
- Department of Food Science and Technology, National Nutrition and Food Technology Research Institute, Faculty of Nutrition Science and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Salam A. Ibrahim
- Food Microbiology and Biotechnology Laboratory, Food and Nutritional Sciences Program, College of Agriculture and Environmental Sciences, North Carolina A & T State University, Greensboro, North Carolina, USA
| | - Azita Hekmatdoost
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hedayat Hosseini
- Department of Food Science and Technology, National Nutrition and Food Technology Research Institute, Faculty of Nutrition Science and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sahar Sabahi
- Department of Nutrition, School of Allied Medical Sciences, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Elham Sheykhsaran
- Department of Medical Bacteriology and Virology, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Mahdi Asghari Ozma
- Department of Medical Bacteriology and Virology, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Masoud Lahouty
- Department of Microbiology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran
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12
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Landaas VØ, Skjerven HO, Carlsen KCL, Størdal K, Håland G. Home-Based Double-Blind, Placebo-Controlled Challenges for Diagnosis of Delayed Gluten/Milk Hypersensitivity in Children. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. IN PRACTICE 2024; 12:652-659.e5. [PMID: 38154555 DOI: 10.1016/j.jaip.2023.12.032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/04/2023] [Revised: 12/12/2023] [Accepted: 12/18/2023] [Indexed: 12/30/2023]
Abstract
BACKGROUND Delayed hypersensitivity to gluten and milk protein is frequently reported but may be difficult to diagnose. OBJECTIVE We aimed to explore if a method of home-based double-blind placebo-controlled food challenges (H-FC) can identify and reduce unnecessary elimination diets in children. METHODS We included 73 of 92 children aged 1 to 17 years referred to a tertiary allergy clinic from 2011 to 2021 due to self-reported, delayed symptoms to gluten or milk. The children were randomized to H-FC, receiving gluten/milk protein or placebo for 5 to 7 days in a double-blind crossover manner, separated by 3 washout weeks. Patients/parents recorded symptoms using standardized forms. Two crossover periods were used from 2011 to 2016 and 3 periods from 2017 to 2021. A positive challenge required significantly more symptoms during the active period versus the placebo period. After the challenge, reintroduction of milk/gluten was assessed by a follow-up interview. The primary outcome was the proportion of children with a positive challenge. RESULTS The children, with a mean age of 11 years, had followed a strict gluten-free or milk-protein-free diet for a median duration of 24 months (range: 3-180 months). A positive challenge was observed in 18 of 73 children (25%), more often using 2 (35%) compared with 3 challenge periods (12%). At follow-up, 44 of 55 (80%) children with a negative challenge had successfully reintroduced milk/gluten. CONCLUSIONS H-FC may be an effective method in avoiding unnecessary elimination diets in children. Only 25% of the challenges were positive, and 80% of the children with negative challenges succeeded in reintroducing the food. Three challenge periods may be necessary to reduce false-positive outcomes.
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Affiliation(s)
- Vibeke Østberg Landaas
- Division of Child and Adolescent Medicine, Oslo University Hospital, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
| | - Håvard Ove Skjerven
- Division of Child and Adolescent Medicine, Oslo University Hospital, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Karin C Lødrup Carlsen
- Division of Child and Adolescent Medicine, Oslo University Hospital, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Ketil Størdal
- Division of Child and Adolescent Medicine, Oslo University Hospital, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Geir Håland
- Division of Child and Adolescent Medicine, Oslo University Hospital, Oslo, Norway
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13
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Nordin E, Landberg R, Hellström PM, Brunius C. Exploration of differential responses to FODMAPs and gluten in people with irritable bowel syndrome- a double-blind randomized cross-over challenge study. Metabolomics 2024; 20:21. [PMID: 38347192 PMCID: PMC10861383 DOI: 10.1007/s11306-023-02083-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Accepted: 12/19/2023] [Indexed: 02/15/2024]
Abstract
INTRODUCTION There is large variation in response to diet in irritable bowel syndrome (IBS) and determinants for differential response are poorly understood. OBJECTIVES Our aim was to investigate differential clinical and molecular responses to provocation with fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs) and gluten in individuals with IBS. METHODS Data were used from a crossover study with week-long interventions with either FODMAPs, gluten or placebo. The study also included a rapid provocation test. Molecular data consisted of fecal microbiota, short chain fatty acids, and untargeted plasma metabolomics. IBS symptoms were evaluated with the IBS severity scoring system. IBS symptoms were modelled against molecular and baseline questionnaire data, using Random Forest (RF; regression and clustering), Parallel Factor Analysis (PARAFAC), and univariate methods. RESULTS Regression and classification RF models were in general of low predictive power (Q2 ≤ 0.22, classification rate < 0.73). Out of 864 clustering models, only 2 had significant associations to clusters (0.69 < CR < 0.73, p < 0.05), but with no associations to baseline clinical measures. Similarly, PARAFAC revealed no clear association between metabolome data and IBS symptoms. CONCLUSION Differential IBS responses to FODMAPs or gluten exposures could not be explained from clinical and molecular data despite extensive exploration with different data analytical approaches. The trial is registered at www. CLINICALTRIALS gov as NCT03653689 31/08/2018.
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Affiliation(s)
- Elise Nordin
- Department of Life Sciences, Division of Food and Nutrition Science, Chalmers University of Technology, 412 96, Gothenburg, Sweden.
| | - Rikard Landberg
- Department of Life Sciences, Division of Food and Nutrition Science, Chalmers University of Technology, 412 96, Gothenburg, Sweden
| | - Per M Hellström
- Department of Medical Sciences, Gastroenterology/Hepatology, Uppsala University, 75185, Uppsala, Sweden
| | - Carl Brunius
- Department of Life Sciences, Division of Food and Nutrition Science, Chalmers University of Technology, 412 96, Gothenburg, Sweden
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14
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de Graaf MCG, Lawton CL, Croden F, Smolinska A, Winkens B, Hesselink MAM, van Rooy G, Weegels PL, Shewry PR, Houghton LA, Witteman BJM, Keszthelyi D, Brouns FJPH, Dye L, Jonkers DMAE. The effect of expectancy versus actual gluten intake on gastrointestinal and extra-intestinal symptoms in non-coeliac gluten sensitivity: a randomised, double-blind, placebo-controlled, international, multicentre study. Lancet Gastroenterol Hepatol 2024; 9:110-123. [PMID: 38040019 DOI: 10.1016/s2468-1253(23)00317-5] [Citation(s) in RCA: 18] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Revised: 09/07/2023] [Accepted: 09/12/2023] [Indexed: 12/03/2023]
Abstract
BACKGROUND Many individuals without coeliac disease or wheat allergy reduce their gluten intake because they believe that gluten causes their gastrointestinal symptoms. Symptoms could be affected by negative expectancy. Therefore, we aimed to investigate the effects of expectancy versus actual gluten intake on symptoms in people with non-coeliac gluten sensitivity (NCGS). METHODS This randomised, double-blind, placebo-controlled, international, multicentre study was done at the University of Leeds (Leeds, UK), Maastricht University (Maastricht, the Netherlands), and Wageningen University and Research (Wageningen, the Netherlands). People aged 18-70 years with self-reported NCGS (ie, gastrointestinal symptoms within 8 h of gluten consumption) without coeliac disease and wheat allergy were recruited. Participants had to follow a gluten-free or gluten-restricted diet for at least 1 week before (and throughout) study participation and had to be asymptomatic or mildly symptomatic (overall gastrointestinal symptom score ≤30 mm on the Visual Analogue Scale [VAS]) while on the diet. Participants were randomly assigned (1:1:1:1; blocks of eight; stratified by site and gender) to one of four groups based on the expectation to consume gluten-containing (E+) or gluten-free (E-) oat bread for breakfast and lunch (two slices each) and actual intake of gluten-containing (G+) or gluten-free (G-) oat bread. Participants, investigators, and those assessing outcomes were masked to the actual gluten assignment, and participants were also masked to the expectancy part of the study. The primary outcome was overall gastrointestinal symptom score on the VAS, which was measured at and corrected for baseline (before breakfast) and hourly for 8 h, with lunch served after 4 h, and analysed per-protocol. Safety analysis included all participants incorporated in the per-protocol analysis. The study is registered at ClinicalTrials.gov, NCT05779358, and has ended. FINDINGS Between Oct 19, 2018, and Feb 14, 2022, 165 people were screened and 84 were randomly assigned to E+G+ (n=21), E+G- (n=21), E-G+ (n=20), or E-G- (n=22). One person in the E+G+ group was excluded due to not following test day instructions, leaving 83 participants in the per-protocol analysis. Median age was 27·0 years (IQR 21·0-45·0), 71 (86%) of 83 people were women, and 12 (14%) were men. Mean overall gastrointestinal symptom score was significantly higher for E+G+ (16·6 mm [95% CI 13·1 to 20·0]) than for E-G+ (6·9 mm [3·5 to 10·4]; difference 9·6 mm [95% CI 3·0 to 16·2], p=0·0010) and E-G- (7·4 mm [4·2 to 10·7]; difference 9·1 mm [2·7 to 15·6], p=0·0016), but not for E+G- (11·7 mm [8·3 to 15·1]; difference 4·9 mm [-1·7 to 11·5], p=0·28). There was no difference between E+G- and E-G+ (difference 4·7 mm [-1·8 to 11·3], p=0·33), E+G- and E-G- (difference 4·2 mm [-2·2 to 10·7], p=0·47), and E-G+ and E-G- (difference -0·5 mm [-7·0 to 5·9], p=1·0). Adverse events were reported by two participants in the E+G- group (itching jaw [n=1]; feeling lightheaded and stomach rumbling [n=1]) and one participant in the E-G+ group (vomiting). INTERPRETATION The combination of expectancy and actual gluten intake had the largest effect on gastrointestinal symptoms, reflecting a nocebo effect, although an additional effect of gluten cannot be ruled out. Our results necessitate further research into the possible involvement of the gut-brain interaction in NCGS. FUNDING Government of the Netherlands Topsector Agri & Food Top Consortium for Knowledge and Innovation, AB Mauri Global Bakery Ingredients, Baking Industry Research Trust, Borgesius-Albert Heijn, CSM Innovation Centre, the International Maize and Wheat Improvement Center (CIMMYT), DSM Food Specialties, Fazer, Healthgrain Forum, the International Association for Cereal Science and Technology, the International Wheat Gluten Association, Lantmännen, Mondelez International, Nederlands Bakkerij Centrum, Nutrition & Santé, Puratos, Rademaker, Sonneveld Group, and Zeelandia HJ Doeleman.
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Affiliation(s)
- Marlijne C G de Graaf
- Department of Gastroenterology-Hepatology, Maastricht University Medical Center+, Maastricht, Netherlands; NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, Netherlands
| | | | - Fiona Croden
- School of Psychology, University of Leeds, Leeds, UK
| | - Agnieszka Smolinska
- NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, Netherlands; Department of Pharmacology and Toxicology, Maastricht University, Maastricht, Netherlands
| | - Bjorn Winkens
- Department of Methodology and Statistics, Care and Public Health Research Institute, Maastricht University, Maastricht, Netherlands
| | - Martine A M Hesselink
- Department of Gastroenterology-Hepatology, Maastricht University Medical Center+, Maastricht, Netherlands; NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, Netherlands
| | - Gonny van Rooy
- Department of Gastroenterology-Hepatology, Maastricht University Medical Center+, Maastricht, Netherlands; NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, Netherlands
| | - Peter L Weegels
- Laboratory of Food Chemistry, Wageningen University and Research, Wageningen, Netherlands; European Bakery Innovation Centre, Sonneveld Group, Papendrecht, Netherlands
| | | | - Lesley A Houghton
- Division of Gastroenterology and Surgical Sciences, Leeds Institute of Medical Research, University of Leeds, Leeds, UK; Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL, USA
| | - Ben J M Witteman
- Division of Human Nutrition, Wageningen University and Research, Wageningen, Netherlands; Division of Gastroenterology-Hepatology, Gelderse Vallei Hospital, Ede, Netherlands
| | - Daniel Keszthelyi
- Department of Gastroenterology-Hepatology, Maastricht University Medical Center+, Maastricht, Netherlands; NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, Netherlands
| | - Fred J P H Brouns
- NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, Netherlands; Department of Human Biology, Maastricht University, Maastricht, Netherlands
| | - Louise Dye
- School of Psychology, University of Leeds, Leeds, UK; School of Food Science and Nutrition, University of Leeds, Leeds, UK
| | - Daisy M A E Jonkers
- Department of Gastroenterology-Hepatology, Maastricht University Medical Center+, Maastricht, Netherlands; NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, Netherlands.
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15
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Shiha MG, Raju SA, Penny HA, Sanders DS. Non-coeliac gluten sensitivity: from Salerno to Rome. Lancet Gastroenterol Hepatol 2024; 9:94-95. [PMID: 38040020 DOI: 10.1016/s2468-1253(23)00358-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2023] [Revised: 10/09/2023] [Accepted: 10/10/2023] [Indexed: 12/03/2023]
Affiliation(s)
- Mohamed G Shiha
- Academic Unit of Gastroenterology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield S10 2JF, UK; Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, Sheffield, UK
| | - Suneil A Raju
- Academic Unit of Gastroenterology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield S10 2JF, UK; Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, Sheffield, UK
| | - Hugo A Penny
- Academic Unit of Gastroenterology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield S10 2JF, UK; Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, Sheffield, UK
| | - David S Sanders
- Academic Unit of Gastroenterology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield S10 2JF, UK; Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, Sheffield, UK.
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16
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Seidita A, Mansueto P, Giuliano A, Carroccio A. Nonceliac gluten-related disorders. PEDIATRIC AND ADULT CELIAC DISEASE 2024:261-282. [DOI: 10.1016/b978-0-443-13359-6.00022-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Brouns F, Van Haaps A, Keszthelyi D, Venema K, Bongers M, Maas J, Mijatovic V. Diet associations in endometriosis: a critical narrative assessment with special reference to gluten. Front Nutr 2023; 10:1166929. [PMID: 37731404 PMCID: PMC10507348 DOI: 10.3389/fnut.2023.1166929] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Accepted: 08/21/2023] [Indexed: 09/22/2023] Open
Abstract
Endometriosis is characterized by the presence of endometrium-like tissue outside the uterus. The etiology remains largely unknown. Despite adequate treatment, patients can still experience symptoms or side effects resulting in therapy incompliance and in self-management strategies such as dietary measures is increasing. A gluten free diet is thought to be contributory in reducing endometriosis-related pain, thereby optimizing quality of life. However, data is conflicting and currently provides no evidence for causality. This narrative review aims to put the effect of dietary self-management strategies on endometriosis in a balanced perspective, especially the effect of gluten and a gluten free diet. Several studies have found a strong overlap in symptoms, metabolic and immune responses associated with endometriosis and those associated with celiac disease, ulcerative colitis, Crohn's disease, irritable bowel syndrome and non-celiac wheat sensitivity. However, it remains unclear whether these diseases and/or disorders are causal to an increased risk of endometriosis. Some studies have found a positive effect on the risk of endometriosis, endometriosis-related symptoms and quality of life (QoL) when women either avoided certain nutrients or foods, or applied a specific nutrient supplementation. This includes the avoidance of red meat, an increasing intake of foods rich in anti-oxidants, omega-3, micronutrients and dietary fibers (e.g., fruit, vegetables) and the appliance of a gluten free diet. However, data from the available studies were generally graded of low quality and it was noted that placebo and/or nocebo effects influenced the reported positive effects. In addition, such effects were no longer seen when adjusting for confounders such as overweight, when a translation was made from in vitro to in vivo, or when the nutrients were not supplemented as isolated sources but as part of a mixed daily diet. Finally, some studies showed that long-term adherence to a gluten free diet is often associated with an impaired diet quality and nutrient intake, leading to negative health outcomes and reduced QoL. Concluding, scientific evidence on the efficacy of dietary interventions on well-defined clinical endpoints of endometriosis is lacking and recommending a gluten free diet to women solely diagnosed with endometriosis should therefore not be advised.
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Affiliation(s)
- Fred Brouns
- Department of Human Biology, School for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, Netherlands
| | - Annelotte Van Haaps
- Endometriosis Center, Amsterdam University Medical Centers, Academic Medical Center, Amsterdam, Netherlands
- Amsterdam Reproduction and Development Research Institute, Amsterdam, Netherlands
| | - Daniel Keszthelyi
- Division of Gastroenterology-Hepatology, Department of Internal Medicine, School for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, Netherlands
| | - Koen Venema
- Centre for Healthy Eating & Food Innovation (HEFI), Maastricht University, Maastricht, Netherlands
| | - Marlies Bongers
- Department of Obstetrics and Gynecology, Máxima Medical Center, Veldhoven, Netherlands
- Grow-School of Oncology and Reproduction, Maastricht University, Maastricht, Netherlands
| | - Jacques Maas
- Grow-School of Oncology and Reproduction, Maastricht University, Maastricht, Netherlands
- Department of Obstetrics and Gynaecology MUMC+, Maastricht, Netherlands
| | - Velja Mijatovic
- Endometriosis Center, Amsterdam University Medical Centers, Academic Medical Center, Amsterdam, Netherlands
- Amsterdam Reproduction and Development Research Institute, Amsterdam, Netherlands
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18
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Mansueto P, Seidita A, Soresi M, Giuliano A, Riccio G, Volta U, Caio G, La Blasca F, Disclafani R, De Giorgio R, Carroccio A. Anemia in non-celiac wheat sensitivity: Prevalence and associated clinical and laboratory features. Dig Liver Dis 2023; 55:735-742. [PMID: 36535870 DOI: 10.1016/j.dld.2022.11.022] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Revised: 11/28/2022] [Accepted: 11/29/2022] [Indexed: 05/29/2023]
Abstract
BACKGROUND Patients suffering from non-celiac wheat sensitivity (NCWS) frequently report extra-intestinal symptoms, such as anemia. AIMS We investigated the prevalence and associated clinical features of anemia in NCWS patients. METHODS Data from 244 NCWS patients, diagnosed by double-blind placebo-controlled wheat challenge, were retrospectively reviewed and compared with 2 control groups (celiac disease (CD) and irritable bowel syndrome (IBS)). Furthermore, 31 NCWS anemic patients were prospectively re-evaluated after at least 12 months on the "strict" wheat-free diet (WFD). RESULTS Anemia prevalence in NCWS patients was 34.8% (mean hemoglobin 10.4 ± 1.4 g/dl), significantly higher than in IBS (17.4%, P = 0.03), but not in CD ones. The NCWS group, on the whole, had sideropenic-like features with low serum iron and altered iron deposits. Both anemia prevalence and sideropenic-like features were more evident in CD than in NCWS patients, whereas only a few IBS subjects showed such features. Significant differences were found in anemic vs non-anemic NCWS patients as regards to female sex, diagnostic delay, poly/hypermenorrhea, iron deficiency, and higher TSH values. A long-term WFD significantly reduced anemia and improved iron metabolism. CONCLUSION Microcytic/hypochromic anemia and altered iron metabolism occur frequently in NCWS and can be treated with a long-term strict WFD. NCWS should be included in differential diagnosis of anemic patients with "functional gastrointestinal troubles".
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Affiliation(s)
- Pasquale Mansueto
- Unit of Internal Medicine, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127, Palermo, Italy
| | - Aurelio Seidita
- Unit of Internal Medicine, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127, Palermo, Italy
| | - Maurizio Soresi
- Unit of Internal Medicine, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127, Palermo, Italy
| | - Alessandra Giuliano
- Unit of Internal Medicine, "V. Cervello" Hospital, Ospedali Riuniti "Villa Sofia-Cervello", 90146, Palermo, Italy; Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127, Palermo, Italy
| | - Giorgia Riccio
- Unit of Internal Medicine, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127, Palermo, Italy
| | - Umberto Volta
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40138, Bologna, Italy
| | - Giacomo Caio
- Department of Translational Medicine, University of Ferrara, 44121, Ferrara, Italy
| | - Francesco La Blasca
- Unit of Internal Medicine, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127, Palermo, Italy
| | - Rosaria Disclafani
- Istituto Zooprofilattico Sperimentale della Sicilia (IZSS), 90129, Palermo, Italy
| | - Roberto De Giorgio
- Department of Translational Medicine, University of Ferrara, 44121, Ferrara, Italy
| | - Antonio Carroccio
- Unit of Internal Medicine, "V. Cervello" Hospital, Ospedali Riuniti "Villa Sofia-Cervello", 90146, Palermo, Italy; Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127, Palermo, Italy.
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19
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Jossen J, Lebwohl B. Non-celiac Gluten Intolerance: A Call to Clarify. Dig Dis Sci 2023; 68:1084-1085. [PMID: 36662340 DOI: 10.1007/s10620-022-07802-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/16/2022] [Indexed: 01/21/2023]
Affiliation(s)
- Jacqueline Jossen
- Departments of Medicine and Pediatrics, The Celiac Disease Center at Columbia University, 180 Fort Washington Avenue, Suite 936, New York, NY, 10032, USA
| | - Benjamin Lebwohl
- Departments of Medicine and Pediatrics, The Celiac Disease Center at Columbia University, 180 Fort Washington Avenue, Suite 936, New York, NY, 10032, USA.
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20
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Seidita A, Mansueto P, Giuliano A, Chiavetta M, Mandreucci F, Soresi M, Pistone M, Compagnoni S, Castellucci D, Bisso G, Faraci F, Maestri S, Disclafani R, Sapone A, Fasano A, Carroccio A. Potential tolerability of ancient grains in non-celiac wheat sensitivity patients: A preliminary evaluation. Front Med (Lausanne) 2022; 9:995019. [PMID: 36250065 PMCID: PMC9554215 DOI: 10.3389/fmed.2022.995019] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Accepted: 09/13/2022] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND AND AIMS A wheat-free diet (WFD) represents the elective treatment for Non-celiac Wheat Sensitivity (NCWS) patients. Preliminary reports have shown a possible better tolerability of ancient grains in these subjects. The aim of this observational study was to evaluate the frequency of consumption of ancient grains and its correlation with clinical manifestations in NCWS patients. METHODS 223 NCWS patients were recruited, and their consumption of ancient grains was monitored. Participants were first administered a modified version of the Pavia/Biagi questionnaire to investigate their adherence to "modern WFD." The appearance/exacerbation of symptoms after ingestion of ancient grains was then assessed with WHO toxicity grading scale. RESULTS 50.2% of the recruited patients reported consuming ancient grains before NCWS diagnosis; the diagnostic delay in this group was significantly higher than in non-consumers [median (range) 72 (6-612) vs. 60 months (3-684), P = 0.03] and these patients reported lower frequency of constipation (P = 0.04). Of the 107 patients with optimal adherence to modern WFD, 14 reported eating ancient wheat after NCWS diagnosis. Among them, 5 reported milder symptoms than those caused by modern wheat intake and 3 had an excellent tolerability without symptoms. Timilia/Tumminia variety was the most frequently used ancient grain. CONCLUSIONS NCWS patients who consume ancient grains may receive a late diagnosis due to the possible clinical benefit (tolerability) obtained with these grains. Even after diagnosis, 10% of the patients still consumed ancient grains and had mild or no symptoms. Further studies are required to define the pathophysiological mechanism behind their putative greater tolerability.
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Affiliation(s)
- Aurelio Seidita
- Unit of Internal Medicine, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy
| | - Pasquale Mansueto
- Unit of Internal Medicine, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy
| | - Alessandra Giuliano
- Unit of Internal Medicine, “V. Cervello” Hospital, Ospedali Riuniti “Villa Sofia-Cervello”, Palermo, Italy
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy
| | - Marta Chiavetta
- Unit of Internal Medicine, “V. Cervello” Hospital, Ospedali Riuniti “Villa Sofia-Cervello”, Palermo, Italy
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy
| | - Francesca Mandreucci
- Unit of Internal Medicine, “V. Cervello” Hospital, Ospedali Riuniti “Villa Sofia-Cervello”, Palermo, Italy
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy
| | - Maurizio Soresi
- Unit of Internal Medicine, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy
| | - Mattia Pistone
- Unit of Internal Medicine, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy
| | - Stella Compagnoni
- Unit of Internal Medicine, “V. Cervello” Hospital, Ospedali Riuniti “Villa Sofia-Cervello”, Palermo, Italy
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy
| | - Daniele Castellucci
- Unit of Internal Medicine, “V. Cervello” Hospital, Ospedali Riuniti “Villa Sofia-Cervello”, Palermo, Italy
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy
| | - Gianluca Bisso
- Unit of Internal Medicine, “V. Cervello” Hospital, Ospedali Riuniti “Villa Sofia-Cervello”, Palermo, Italy
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy
| | - Francesco Faraci
- Unit of Internal Medicine, “V. Cervello” Hospital, Ospedali Riuniti “Villa Sofia-Cervello”, Palermo, Italy
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy
| | - Salvatore Maestri
- Unit of Internal Medicine, “V. Cervello” Hospital, Ospedali Riuniti “Villa Sofia-Cervello”, Palermo, Italy
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy
| | | | - Anna Sapone
- Division of Pediatric Gastroenterology and Nutrition, Mucosal Immunology and Biology Research Center, Center for Celiac Research, Harvard Medical School, Massachusetts General Hospital for Children, Boston, MA, United States
| | - Alessio Fasano
- Division of Pediatric Gastroenterology and Nutrition, Mucosal Immunology and Biology Research Center, Center for Celiac Research, Harvard Medical School, Massachusetts General Hospital for Children, Boston, MA, United States
| | - Antonio Carroccio
- Unit of Internal Medicine, “V. Cervello” Hospital, Ospedali Riuniti “Villa Sofia-Cervello”, Palermo, Italy
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy
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21
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Zimmermann J, Longin FH, Schweinlin A, Basrai M, Bischoff SC. No Difference in Tolerance between Wheat and Spelt Bread in Patients with Suspected Non-Celiac Wheat Sensitivity. Nutrients 2022; 14:nu14142800. [PMID: 35889757 PMCID: PMC9319925 DOI: 10.3390/nu14142800] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Revised: 06/30/2022] [Accepted: 07/05/2022] [Indexed: 12/03/2022] Open
Abstract
Individuals with suspected non-celiac wheat sensitivity (NCWS) often report better tolerance of spelt (Triticum aestivum ssp. spelta) compared to wheat (Triticum aestivum ssp. aestivum) bakery products. This experience has neither been validated nor explained on a molecular level. Therefore, we performed blinded wheat and spelt bread challenge in this patient group. Twenty-four adults with a history of NCWS but suspected spelt tolerance were challenged in a single-blinded crossover design over six weeks with six different study breads each at 300 g per day for 4 days followed by a washout phase of 3 days. Study breads comprised spelt and wheat breads made either after a traditional (T) or a current (C) recipe, resulting in four bread types plus a gluten-free bread with 1.5% added oligosaccharides (+FODMAP) and a gluten-free bread with 5% added wheat gluten (+Gluten). The main outcome parameter was the Irritable Bowel Syndrome—Severity Scoring System, which was higher than self-estimated by the participants after spelt bread consumption (p = 0.002 for T; p = 0.028 for C) and lower for wheat bread (p = 0.052 for T; p = 0.007 for C), resulting in no difference between wheat and spelt bread tolerance. The +FODMAP bread was better tolerated than both T breads (p = 0.003 for spelt; p = 0.068 for wheat) and equally well tolerated as both C breads and +Gluten breads after normalization to the washout scores. Neither signs of inflammation nor markers for intestinal barrier integrity were influenced. Our data do not confirm, on an objective basis, the differences in expected symptoms resulting from wheat and spelt products, suggesting a strong nocebo effect for wheat and a placebo effect for spelt.
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Affiliation(s)
- Julia Zimmermann
- Institute of Nutritional Medicine, University of Hohenheim, Fruwirthstrasse 12, 70599 Stuttgart, Germany; (J.Z.); (A.S.); (M.B.)
| | - Friedrich H. Longin
- State Plant Breeding Institute, University of Hohenheim, Fruwirthstrasse 21, 70599 Stuttgart, Germany;
| | - Anna Schweinlin
- Institute of Nutritional Medicine, University of Hohenheim, Fruwirthstrasse 12, 70599 Stuttgart, Germany; (J.Z.); (A.S.); (M.B.)
| | - Maryam Basrai
- Institute of Nutritional Medicine, University of Hohenheim, Fruwirthstrasse 12, 70599 Stuttgart, Germany; (J.Z.); (A.S.); (M.B.)
| | - Stephan C. Bischoff
- Institute of Nutritional Medicine, University of Hohenheim, Fruwirthstrasse 12, 70599 Stuttgart, Germany; (J.Z.); (A.S.); (M.B.)
- Correspondence: ; Tel.: +49-711-459-24100
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22
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Tye-Din JA. Editorial: lack of gastrointestinal symptoms caused by gluten in patients without coeliac disease-time to ditch the 'gluten' from 'non-coeliac gluten sensitivity'. Aliment Pharmacol Ther 2022; 56:340-341. [PMID: 35748828 DOI: 10.1111/apt.16951] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Affiliation(s)
- Jason A Tye-Din
- Immunology Division, The Walter and Eliza Hall Institute, Parkville, Victoria, Australia.,Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia.,Department of Gastroenterology, The Royal Melbourne Hospital, Parkville, Victoria, Australia.,Centre for Food & Allergy Research, Murdoch Children's Research Institute, Parkville, Victoria, Australia
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23
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Barberio B, Savarino EV, Black CJ, Ford AC. Adverse events in trials of licensed drugs for irritable bowel syndrome with constipation or diarrhea: Systematic review and meta-analysis. Neurogastroenterol Motil 2022; 34:e14279. [PMID: 34672052 DOI: 10.1111/nmo.14279] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Revised: 09/21/2021] [Accepted: 09/27/2021] [Indexed: 12/14/2022]
Abstract
BACKGROUND Nocebo effects occurring in patients receiving placebo frequently impact on adverse events reported in randomized controlled trials (RCTs) in irritable bowel syndrome (IBS). Therefore, we conducted a systematic review and meta-analysis to assess the proportion of patients randomized to placebo or active drug experiencing any adverse event in trials of licensed drugs for IBS with constipation (IBS-C) or diarrhea (IBS-D), and to estimate the risk of developing adverse events among patients randomized to placebo. METHODS We searched MEDLINE, EMBASE CLASSIC and EMBASE, and the Cochrane central register of controlled trials (through June 2021) to identify RCTs comparing licensed drugs with placebo in adults with IBS-C or IBS-D. We generated Forest plots of pooled adverse event rates in both active drug and placebo arms and pooled risk differences (RDs) with 95% confidence intervals (CIs). KEY RESULTS There were 21 RCTs of licensed drugs versus placebo in IBS-C (5953 patients placebo) and 17 in IBS-D (3854 patients placebo). Overall, 34.9% and 46.9% of placebo patients in IBS-C and IBS-D trials, respectively, developed at least one adverse event, with a statistically significantly higher risk of any adverse event and withdrawal due to an adverse event with active drug. In IBS-C and IBS-D trials, rates of each individual adverse event were generally higher with active drug. However, in IBS-C trials, only diarrhea or headache was significantly more common with active drug (RD 0.066 (95% CI 0.043-0.088) and RD 0.011 (95% CI 0.002-0.021), respectively), and in IBS-D trials only constipation, nausea, or abdominal pain (RD 0.096 (95% CI 0.054-0.138), 0.014 (95% CI 0.002-0.027), and 0.018 (95% CI 0.002-0.034), respectively). CONCLUSIONS & INFERENCES Patients with IBS randomized to placebo have a high risk of reporting adverse events, which might relate to both nocebo and non-nocebo factors. Although patients' expectations and psychosocial factors may be involved, further understanding of the mechanisms are important to control or optimize these effects in RCTs, as well as in clinical practice.
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Affiliation(s)
- Brigida Barberio
- Department of Surgery, Oncology and Gastroenterology (DISCOG), Gastroenterology Unit, University of Padova-Azienda Ospedaliera di Padova, Padova, Italy
| | - Edoardo V Savarino
- Department of Surgery, Oncology and Gastroenterology (DISCOG), Gastroenterology Unit, University of Padova-Azienda Ospedaliera di Padova, Padova, Italy
| | - Christopher J Black
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK.,Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
| | - Alexander C Ford
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK.,Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
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24
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Crawley C, Savino N, Halby C, Sander SD, Andersen AN, Arumugam M, Murray J, Christensen R, Husby S. The effect of gluten in adolescents and young adults with gastrointestinal symptoms: a blinded randomised cross-over trial. Aliment Pharmacol Ther 2022; 55:1116-1127. [PMID: 35352373 PMCID: PMC9313792 DOI: 10.1111/apt.16914] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2021] [Revised: 09/17/2021] [Accepted: 03/20/2022] [Indexed: 12/14/2022]
Abstract
BACKGROUND The popularity of the gluten-free diet and sales of gluten-free products have increased immensely. AIMS To investigate whether gluten induces gastrointestinal symptoms, measured by self-reported questionnaires, as well as mental health symptoms in adolescents from a population-based cohort. METHODS The eligible participants (n = 273) were recruited from a population-based cohort of 1266 adolescents and had at least four different gastrointestinal symptoms. Phase one (n = 54) was a run-in phase where the participants lived gluten-free for 2 weeks. If they improved they continued to phase 2 (n = 33), a blinded randomised cross-over trial. Participants were blindly randomised either to start with 7 days of gluten, eating two granola bars containing 10 g of gluten or to 7 days on placebo, eating two granola bars without gluten, followed by the reverse and separated by a 7-day washout period. The effects of the intervention on gastrointestinal symptoms and mental health symptoms were assessed. RESULTS In total, 54/273 participants entered the run-in phase and 35 were eligible for randomization. A total of 33 were randomised and 32 completed the trial. The median age was 20.3 (IQR 19.2-20.9) and 32/33 participants were females. Compared with a placebo, gluten did not induce gastrointestinal symptoms. The difference in the average VAS was -0.01 (95% confidence interval -2.07 to 2.05). Nor did we find a difference in the outcomes measuring mental health. CONCLUSION Compared with placebo, adding gluten to the diet did not induce gastrointestinal symptoms or worsened mental health in adolescents recruited from a population-based cohort. The trial registration number is NCT04639921.
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Affiliation(s)
- Caecilie Crawley
- Hans Christian Andersen Children’s HospitalOdense University HospitalOdenseDenmark,Department of Clinical ResearchUniversity of Southern DenmarkOdenseDenmark
| | - Nadia Savino
- Hans Christian Andersen Children’s HospitalOdense University HospitalOdenseDenmark,Department of Clinical ResearchUniversity of Southern DenmarkOdenseDenmark
| | - Cecilie Halby
- Hans Christian Andersen Children’s HospitalOdense University HospitalOdenseDenmark,Department of Clinical ResearchUniversity of Southern DenmarkOdenseDenmark
| | | | | | - Manimozhiyan Arumugam
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical SciencesUniversity of CopenhagenCopenhagenDenmark,Department of Gastroenterology and HepatologyOdense University HospitalOdenseDenmark
| | - Joseph Murray
- Division of Gastroenterology and Hepatology, Department of Internal MedicineMayo ClinicRochesterMinnesotaUSA
| | - Robin Christensen
- Section for Biostatistics and Evidence‐Based Research, the Parker InstituteBispebjerg and Frederiksberg HospitalCopenhagenDenmark,Research Unit of Rheumatology, Department of Clinical ResearchUniversity of Southern Denmark, Odense University HospitalOdenseDenmark
| | - Steffen Husby
- Hans Christian Andersen Children’s HospitalOdense University HospitalOdenseDenmark,Department of Clinical ResearchUniversity of Southern DenmarkOdenseDenmark
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25
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Gibson PR, Halmos EP, So D, Yao CK, Varney JE, Muir JG. Diet as a therapeutic tool in chronic gastrointestinal disorders: Lessons from the FODMAP journey. J Gastroenterol Hepatol 2022; 37:644-652. [PMID: 34994019 DOI: 10.1111/jgh.15772] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2021] [Revised: 12/12/2021] [Accepted: 12/24/2021] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND AIM Diet is a powerful tool in the management of gastrointestinal disorders, but developing diet therapies is fraught with challenge. This review discusses key lessons from the FODMAP diet journey. METHODS Published literature and clinical experience were reviewed. RESULTS Key to designing a varied, nutritionally adequate low-FODMAP diet was our accurate and comprehensive database of FODMAP composition, made universally accessible via our user-friendly, digital application. Our discovery that FODMAPs coexist with gluten in cereal products and subsequent gluten/fructan challenge studies in nonceliac gluten-sensitive populations highlighted issues of collinearity in the nutrient composition of food and confirmation bias in the interpretation of dietary studies. Despite numerous challenges in designing, funding, and executing dietary randomized controlled trials, efficacy of the low-FODMAP diet has been repeatedly demonstrated, and confirmed by real-world experience, giving this therapy credibility in the eyes of clinicians and researchers. Furthermore, real-world application of this diet saw the evolution of a safe and effective three-phased approach. Specialist dietitians must deliver this diet to optimize outcomes as they can target and tailor the therapy and to mitigate the key risks of compromising nutritional adequacy and precipitating disordered eating behaviors, skills outside the gastroenterologist's standard tool kit. While concurrent probiotics are ineffective, specific fiber supplements may improve short-term and long-term outcomes. CONCLUSIONS The FODMAP diet is highly effective, but optimal outcomes are contingent on the involvement of a gastroenterological dietitian who can assess, educate, and monitor patients and manage risks associated with implementation of this restrictive diet.
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Affiliation(s)
- Peter R Gibson
- Department of Gastroenterology, Central Clinical School, Monash University and Alfred Health, Melbourne, Victoria, Australia
| | - Emma P Halmos
- Department of Gastroenterology, Central Clinical School, Monash University and Alfred Health, Melbourne, Victoria, Australia
| | - Daniel So
- Department of Gastroenterology, Central Clinical School, Monash University and Alfred Health, Melbourne, Victoria, Australia
| | - Chu K Yao
- Department of Gastroenterology, Central Clinical School, Monash University and Alfred Health, Melbourne, Victoria, Australia
| | - Jane E Varney
- Department of Gastroenterology, Central Clinical School, Monash University and Alfred Health, Melbourne, Victoria, Australia
| | - Jane G Muir
- Department of Gastroenterology, Central Clinical School, Monash University and Alfred Health, Melbourne, Victoria, Australia
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26
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Makharia G, Gibson PR, Bai JC, Karakan T, Lee YY, Collins L, Muir J, Oruc N, Quigley E, Sanders DS, Tuck C, Yurdaydin C, Le Mair A. World Gastroenterology Organisation Global Guidelines: Diet and the Gut. J Clin Gastroenterol 2022; 56:1-15. [PMID: 34860201 DOI: 10.1097/mcg.0000000000001588] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2019] [Accepted: 05/22/2021] [Indexed: 12/10/2022]
Affiliation(s)
- Govind Makharia
- All India Institute of Medical Sciences, Gastroenterology, & Human Nutrition, New Delhi, Delhi, India
| | - Peter R Gibson
- Department of Gastroenterology, Monash University and Alfred Health
| | - Julio C Bai
- University of Salvador and Dr. C. Bonorino Udaondo Gastroenterology Hospital, Buenos Aires, Argentina
| | | | - Yeong Yeh Lee
- University of Science, Malaysia, Kota Bharu, Malaysia
| | - Lyndal Collins
- Department of Gastroenterology, Monash University and Alfred Health
| | - Jane Muir
- Department of Gastroenterology, Monash University and Alfred Health
| | | | | | - David S Sanders
- Royal Hallamshire Hospital and University of Sheffield, Sheffield, UK
| | | | | | - Anton Le Mair
- Medical Guideline Development, ALM Consulting, Amsterdam, The Netherlands
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27
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Dale HF, Johannessen JCH, Brønstad I, Lied GA. Assessment of Markers of Gut Integrity and Inflammation in Non-Celiac Gluten Sensitivity After a Gluten Free-Diet. Int J Gen Med 2021; 14:9459-9470. [PMID: 34916830 PMCID: PMC8668436 DOI: 10.2147/ijgm.s333078] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Accepted: 10/08/2021] [Indexed: 12/12/2022] Open
Abstract
Purpose Markers for gut integrity and inflammation have received increasing interest as intestinal permeability and innate immune system activation are suggested as possible pathophysiological mechanisms in non-celiac gluten sensitivity (NCGS). We aimed to assess relevant biomarkers in NCGS by analyzing serum levels of gut integrity and permeability markers, pro-inflammatory cytokines and antigliadin IgG in patients with suspected NCGS on a gluten-free diet (GFD), and compare them to serum levels in patients with irritable bowel syndrome (IBS) and healthy controls (HC). Patients and Methods Serum samples collected from patients with suspected NCGS on a GFD (n=20, 14 women, 21–62 years), IBS (n=20, 16 women, 24–67 years) and HC (n=20, 14 women, 21–54 years) were analyzed. IBS severity scoring system (IBS-SSS) was applied to evaluate gastrointestinal symptoms. Results The IBS-SSS score was higher in subjects with suspected NCGS and IBS patients compared to HC (p<0.0001). No significant differences were found in the serum levels of any of the gut integrity and permeability markers, cytokines or antigliadin IgG antibodies between the three groups. However, positive correlations were observed between claudin-1 and i-FABP, and between claudin-1 and antigliadin IgG antibodies. Conclusion No differences in serum levels of gut integrity and permeability markers, pro-inflammatory cytokines or antigliadin IgG antibodies were found among patients with suspected NCGS on a GFD, IBS and HC.
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Affiliation(s)
- Hanna Fjeldheim Dale
- Centre for Nutrition, Department of Clinical Medicine, University of Bergen, Bergen, Norway.,Division of Gastroenterology, Department of Medicine, Haukeland University Hospital, Bergen, Norway.,National Centre of Functional Gastrointestinal Disorders, Haukeland University Hospital, Bergen, Norway
| | | | - Ingeborg Brønstad
- Division of Gastroenterology, Department of Medicine, Haukeland University Hospital, Bergen, Norway.,National Centre of Functional Gastrointestinal Disorders, Haukeland University Hospital, Bergen, Norway
| | - Gülen Arslan Lied
- Centre for Nutrition, Department of Clinical Medicine, University of Bergen, Bergen, Norway.,Division of Gastroenterology, Department of Medicine, Haukeland University Hospital, Bergen, Norway.,National Centre of Functional Gastrointestinal Disorders, Haukeland University Hospital, Bergen, Norway
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28
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Mansueto P, Soresi M, Peralta S, Perricone S, La Blasca F, Sichera R, Giambalvo O, Carroccio A. Self-reported nonceliac wheat sensitivity in an outpatient digestive endoscopy center: high frequency but insufficient medical approach. Eur J Gastroenterol Hepatol 2021; 33:e789-e795. [PMID: 34334709 DOI: 10.1097/meg.0000000000002257] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
OBJECTIVE 'Self-reported wheat sensitivity' (SRWS) is a self-reported condition caused by wheat ingestion in the absence of celiac disease or wheat allergy. The aim of the study was to investigate the frequency and characteristics of SRWS in outpatients referred for digestive endoscopy. METHODS The study, performed at the University of Palermo, enrolled 496 outpatients. RESULTS Seven individuals (1.4%) had an already established diagnosis of celiac disease. The questionnaire was administered to the other 489 individuals: 98 subjects (20%) were SRWS, the remaining 391 served as controls (i.e. not-SRWS). SRWS patients were younger (P < 0.001), with a higher percentage of females (P = 0.002) than not-SRWS. 'gastroesophageal reflux disease and ulcer-like dyspepsia' and 'chronic unexplained diarrhea' were more frequently the reasons for the endoscopy study in SRWS than in not-SRWS (P = 0.002, and P = 0.05, respectively). Food allergies/intolerances (P = 0.04), milk allergy/intolerance (P = 0.0001), GERD (P = 0.0001), IBS (0.0001), anxiety (P = 0.005) and depression (P = 0.04) were the previous medical diagnoses reported more frequently in SRWS patients than in not-SRWS. In the SRWS group, 38% of the patients had already undergone previous upper endoscopy and 24% colonoscopy. After these investigations, 58% of SRWS patients received no diagnosis, and the other 42% were informed that they 'were not suffering from celiac disease or wheat allergy'. Finally, 28.6% SRWS patients had followed a gluten-free diet (GFD), and 71.4% of them referred being asymptomatic on GFD. CONCLUSIONS Our data showed a high frequency of SRWS in outpatients referred to a digestive endoscopy center and a lack of medical accuracy in identifying a possible gluten-related disease. REGISTRATION The study was registered on Clinicaltrials.gov (registration number: NCT04154137), accessible at: https://clinicaltrials.gov/ct2/show/NCT04154137?term=non+celiac+wheat&draw=2&rank=1.
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Affiliation(s)
- Pasquale Mansueto
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), Unit of Internal Medicine, University of Palermo
| | - Maurizio Soresi
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), Unit of Internal Medicine, University of Palermo
| | - Sergio Peralta
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), Unit of Gastroenterology, University of Palermo
| | - Simona Perricone
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), Unit of Internal Medicine, University of Palermo
| | - Francesco La Blasca
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), Unit of Internal Medicine, University of Palermo
| | - Roberto Sichera
- Department of Economics, Management and Statistics, University of Palermo
| | - Ornella Giambalvo
- Department of Economics, Management and Statistics, University of Palermo
| | - Antonio Carroccio
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), Unit of Internal Medicine "V. Cervello Hospital", University of Palermo, Italy
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29
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Reuzé A, Delvert R, Perrin L, Benamouzig R, Sabaté JM, Bouchoucha M, Allès B, Touvier M, Hercberg S, Julia C, Kesse-Guyot E. Association between Self-Reported Gluten Avoidance and Irritable Bowel Syndrome: Findings of the NutriNet-Santé Study. Nutrients 2021; 13:4147. [PMID: 34836402 PMCID: PMC8622067 DOI: 10.3390/nu13114147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Revised: 11/14/2021] [Accepted: 11/17/2021] [Indexed: 11/24/2022] Open
Abstract
Self-management of irritable bowel syndrome (IBS) is increasingly focusing on exclusion diets. In particular; patients are showing a significant interest in the gluten-free diet for the treatment of IBS. However; the lack of scientific evidence prevents the establishment of clear dietary guidelines and attention is needed as dietary restriction can lead to potentially adverse effects. This cross-sectional study aims to explore the practice of gluten avoidance in participants identified with IBS in a large cohort of non-celiac French adults. The population included 15,103 participants of the NutriNet-Santé study who completed a functional gastrointestinal disorder questionnaire based on the Rome III criteria to identify IBS in 2013 and a food avoidance questionnaire in 2016. Data on diet and anthropometric and sociodemographic characteristics were collected. Multivariate logistic regression models were used to compare the avoidance of gluten between IBS and non-IBS participants. Participants were mainly women (73.4%) and the mean age in this population was 55.8 ± 13.2 years. Among these individuals, 804 (5.4%) participants were identified as IBS cases. Among them, the prevalence of gluten avoidance was estimated at 14.8%, of which 3.0% reported total avoidance; versus 8.8% and 1.6% in non-IBS participants. After adjustments; gluten avoidance was higher in IBS participants compared to their non-IBS counterparts: (OR = 1.86; 95%CI = 1.21, 2.85) for total and (OR = 1.71; 95%CI = 1.36, 2.14) for partial avoidance. Participants identified with IBS were more associated with gluten avoidance than non-IBS participants. Further studies are needed to explore the long-term consequences of dietary interventions and to provide consistent dietary guidance connected to patient perception.
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Affiliation(s)
- Anouk Reuzé
- Nutritional Epidemiology Research Team (EREN), Sorbonne Paris Cité Epidemiology and Statistics Research Center (CRESS), Inserm U1153, Inrae U1125, Cnam, Université Sorbonne Paris Nord University, 93017 Bobigny, France; (R.D.); (L.P.); (B.A.); (M.T.); (S.H.); (C.J.); (E.K.-G.)
| | - Rosalie Delvert
- Nutritional Epidemiology Research Team (EREN), Sorbonne Paris Cité Epidemiology and Statistics Research Center (CRESS), Inserm U1153, Inrae U1125, Cnam, Université Sorbonne Paris Nord University, 93017 Bobigny, France; (R.D.); (L.P.); (B.A.); (M.T.); (S.H.); (C.J.); (E.K.-G.)
| | - Laëtitia Perrin
- Nutritional Epidemiology Research Team (EREN), Sorbonne Paris Cité Epidemiology and Statistics Research Center (CRESS), Inserm U1153, Inrae U1125, Cnam, Université Sorbonne Paris Nord University, 93017 Bobigny, France; (R.D.); (L.P.); (B.A.); (M.T.); (S.H.); (C.J.); (E.K.-G.)
| | - Robert Benamouzig
- Department of Hepatology and Gastroenterology, Avicenne Hospital (AP-HP), 93017 Bobigny, France; (R.B.); (J.-M.S.); (M.B.)
| | - Jean-Marc Sabaté
- Department of Hepatology and Gastroenterology, Avicenne Hospital (AP-HP), 93017 Bobigny, France; (R.B.); (J.-M.S.); (M.B.)
- Physiopathologie et Pharmacologie Clinique de la Douleur, Ambroise Paré Hospital, 92104 Boulogne Billancourt, France
| | - Michel Bouchoucha
- Department of Hepatology and Gastroenterology, Avicenne Hospital (AP-HP), 93017 Bobigny, France; (R.B.); (J.-M.S.); (M.B.)
| | - Benjamin Allès
- Nutritional Epidemiology Research Team (EREN), Sorbonne Paris Cité Epidemiology and Statistics Research Center (CRESS), Inserm U1153, Inrae U1125, Cnam, Université Sorbonne Paris Nord University, 93017 Bobigny, France; (R.D.); (L.P.); (B.A.); (M.T.); (S.H.); (C.J.); (E.K.-G.)
| | - Mathilde Touvier
- Nutritional Epidemiology Research Team (EREN), Sorbonne Paris Cité Epidemiology and Statistics Research Center (CRESS), Inserm U1153, Inrae U1125, Cnam, Université Sorbonne Paris Nord University, 93017 Bobigny, France; (R.D.); (L.P.); (B.A.); (M.T.); (S.H.); (C.J.); (E.K.-G.)
| | - Serge Hercberg
- Nutritional Epidemiology Research Team (EREN), Sorbonne Paris Cité Epidemiology and Statistics Research Center (CRESS), Inserm U1153, Inrae U1125, Cnam, Université Sorbonne Paris Nord University, 93017 Bobigny, France; (R.D.); (L.P.); (B.A.); (M.T.); (S.H.); (C.J.); (E.K.-G.)
- Department of Public Health, Avicenne Hospital (AP-HP), 93017 Bobigny, France
| | - Chantal Julia
- Nutritional Epidemiology Research Team (EREN), Sorbonne Paris Cité Epidemiology and Statistics Research Center (CRESS), Inserm U1153, Inrae U1125, Cnam, Université Sorbonne Paris Nord University, 93017 Bobigny, France; (R.D.); (L.P.); (B.A.); (M.T.); (S.H.); (C.J.); (E.K.-G.)
- Department of Public Health, Avicenne Hospital (AP-HP), 93017 Bobigny, France
| | - Emmanuelle Kesse-Guyot
- Nutritional Epidemiology Research Team (EREN), Sorbonne Paris Cité Epidemiology and Statistics Research Center (CRESS), Inserm U1153, Inrae U1125, Cnam, Université Sorbonne Paris Nord University, 93017 Bobigny, France; (R.D.); (L.P.); (B.A.); (M.T.); (S.H.); (C.J.); (E.K.-G.)
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Onyimba F, Crowe SE, Johnson S, Leung J. Food Allergies and Intolerances: A Clinical Approach to the Diagnosis and Management of Adverse Reactions to Food. Clin Gastroenterol Hepatol 2021; 19:2230-2240.e1. [PMID: 33493695 DOI: 10.1016/j.cgh.2021.01.025] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2020] [Revised: 10/18/2020] [Accepted: 01/18/2021] [Indexed: 12/12/2022]
Abstract
Food allergy is an aberrant immunological response to food antigen, which can result in potentially life-threatening reactions. It is often challenging to differentiate food allergy from other adverse reactions to food because their presentations can be indistinguishable. The purpose of this article is to give an overview of the classification, evaluation, and management of adverse food reactions, key differentiating features of food allergy, roles and limitations of various food allergy testing, and promising areas of emerging research. Case studies are used to highlight some of the clinical pearls in diagnosing and managing food-related diseases.
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Affiliation(s)
- Frances Onyimba
- University of Maryland School of Medicine, Baltimore, Maryland.
| | - Sheila E Crowe
- University of California San Diego, La Jolla, California
| | | | - John Leung
- Boston Food Allergy Center, Boston, Massachusetts; Tufts Medical Center, Boston, Massachusetts.
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31
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Haller E, Scarlata K. Diet Interventions for Irritable Bowel Syndrome: Separating the Wheat from the Chafe. Gastroenterol Clin North Am 2021; 50:565-579. [PMID: 34304788 DOI: 10.1016/j.gtc.2021.03.005] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/21/2023]
Abstract
Patients with irritable bowel syndrome (IBS) frequently perceive eating food as a trigger to their gastrointestinal (GI) distress. Several factors involved in driving GI symptoms include malabsorption and fermentation of food substrates, gut microbiota alterations, nocebo and placebo response, and mast cell activation. Nutritional interventions require individualization based on the heterogeneity of symptoms as well as the risk for maladaptive eating patterns that present in those with IBS. Despite the variety of interventions marketed to individuals with IBS, the low Fermentable, Oligo-, Di-Mono-saccharide, and Polyol diet has the most evidence for efficacy in symptom management.
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Affiliation(s)
- Emily Haller
- Division of Gastroenterology and Hepatology, Michigan Medicine, 3912 Taubman Center, 1500 East Medical Center Drive SPC, 5362, Ann Arbor, MI 48109-5362, USA.
| | - Kate Scarlata
- For a Digestive Peace of Mind, LLC Medway, MA 02053, USA. https://twitter.com/KateScarlata_RD
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Cárdenas-Torres FI, Cabrera-Chávez F, Figueroa-Salcido OG, Ontiveros N. Non-Celiac Gluten Sensitivity: An Update. ACTA ACUST UNITED AC 2021; 57:medicina57060526. [PMID: 34073654 PMCID: PMC8224613 DOI: 10.3390/medicina57060526] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2021] [Revised: 05/13/2021] [Accepted: 05/19/2021] [Indexed: 12/12/2022]
Abstract
Non-celiac gluten sensitivity (NCGS) is a clinical entity characterized by the absence of celiac disease and wheat allergy in patients that trigger reproducible symptomatic responses to gluten-containing foods consumption. Due to the lack of sensitive and reproducible biomarkers for NCGS diagnosis, placebo-controlled gluten challenges must be carried out for its diagnosis. The gluten challenges can be either double- or single-blind, for research or clinical practice purposes, respectively. For improving our understanding about the magnitude and relevance of NCGS in different populations, epidemiological studies based on self-report have been carried out. However, the gluten challenge-based prevalence of NCGS remains to be estimated. Since NCGS was recently recognized as a clinical entity, more studies are needed to delve into NCGS pathogenesis, for instance, the molecular interactions between the suspected cereal grain components that trigger NCGS, such as fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs) and amylase and trypsin inhibitors, and the immune system remains to be elucidated. Although still under debate, NCGS patients can be susceptible to only one or more than one of the NCGS triggers. The treatment of NCGS involves the dietary restriction of the suspected triggers of the disease, but there is controversial data about the effectiveness of different dietary interventions such as the gluten-free diet and low-FODMAP diet. Certainly, our understanding of NCGS is improving quickly due to the constant availability of new scientific information on this topic. Thus, the aim of the present narrative review is to present an up-to-date overview on NCGS from epidemiology to current therapy.
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Affiliation(s)
- Feliznando Isidro Cárdenas-Torres
- Doctorate Program in Nutrition Science, Faculty of Nutrition Sciences, University of Sinaloa, Culiacán 80019, Mexico; (F.I.C.-T.); (F.C.-C.)
| | - Francisco Cabrera-Chávez
- Doctorate Program in Nutrition Science, Faculty of Nutrition Sciences, University of Sinaloa, Culiacán 80019, Mexico; (F.I.C.-T.); (F.C.-C.)
| | - Oscar Gerardo Figueroa-Salcido
- Postgraduate in Health Sciences, Division of Biological and Health Sciences, University of Sonora, Hermosillo 83000, Mexico
- Correspondence: (O.G.F.-S.); (N.O.)
| | - Noé Ontiveros
- Clinical and Research Laboratory (LACIUS, URS), Department of Chemical, Biological, and Agricultural Sciences (DC-QB), Division of Sciences and Engineering, University of Sonora, Navojoa 85880, Mexico
- Correspondence: (O.G.F.-S.); (N.O.)
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Gargano D, Appanna R, Santonicola A, De Bartolomeis F, Stellato C, Cianferoni A, Casolaro V, Iovino P. Food Allergy and Intolerance: A Narrative Review on Nutritional Concerns. Nutrients 2021; 13:1638. [PMID: 34068047 PMCID: PMC8152468 DOI: 10.3390/nu13051638] [Citation(s) in RCA: 84] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 05/05/2021] [Accepted: 05/10/2021] [Indexed: 02/07/2023] Open
Abstract
Adverse food reactions include immune-mediated food allergies and non-immune-mediated intolerances. However, this distinction and the involvement of different pathogenetic mechanisms are often confused. Furthermore, there is a discrepancy between the perceived vs. actual prevalence of immune-mediated food allergies and non-immune reactions to food that are extremely common. The risk of an inappropriate approach to their correct identification can lead to inappropriate diets with severe nutritional deficiencies. This narrative review provides an outline of the pathophysiologic and clinical features of immune and non-immune adverse reactions to food-along with general diagnostic and therapeutic strategies. Special emphasis is placed on specific nutritional concerns for each of these conditions from the combined point of view of gastroenterology and immunology, in an attempt to offer a useful tool to practicing physicians in discriminating these diverging disease entities and planning their correct management. We conclude that a correct diagnostic approach and dietary control of both immune- and non-immune-mediated food-induced diseases might minimize the nutritional gaps in these patients, thus helping to improve their quality of life and reduce the economic costs of their management.
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Affiliation(s)
- Domenico Gargano
- Allergy and Clinical Immunology Unit, San Giuseppe Moscati Hospital, 83100 Avellino, Italy; (D.G.); (F.D.B.)
| | - Ramapraba Appanna
- Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, 84081 Baronissi, Italy; (R.A.); (A.S.); (C.S.); (V.C.)
| | - Antonella Santonicola
- Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, 84081 Baronissi, Italy; (R.A.); (A.S.); (C.S.); (V.C.)
| | - Fabio De Bartolomeis
- Allergy and Clinical Immunology Unit, San Giuseppe Moscati Hospital, 83100 Avellino, Italy; (D.G.); (F.D.B.)
| | - Cristiana Stellato
- Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, 84081 Baronissi, Italy; (R.A.); (A.S.); (C.S.); (V.C.)
| | - Antonella Cianferoni
- Division of Allergy and Immunology, The Children’s Hospital of Philadelphia, Perelman School of Medicine at University of Pennsylvania, Philadelphia, PA 19104, USA;
| | - Vincenzo Casolaro
- Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, 84081 Baronissi, Italy; (R.A.); (A.S.); (C.S.); (V.C.)
| | - Paola Iovino
- Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, 84081 Baronissi, Italy; (R.A.); (A.S.); (C.S.); (V.C.)
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Ponzo V, Ferrocino I, Goitre I, Pellegrini M, Bruno M, Astegiano M, Cadario G, Castellana E, Bioletto F, Corvaglia MR, Malfa P, Cocolin L, Ghigo E, Bo S. Non-Celiac Gluten/Wheat Sensitivity: Clinical Characteristics and Microbiota and Mycobiota Composition by Response to the Gluten Challenge Test. Nutrients 2021; 13:nu13041260. [PMID: 33921293 PMCID: PMC8070191 DOI: 10.3390/nu13041260] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Revised: 04/08/2021] [Accepted: 04/09/2021] [Indexed: 12/12/2022] Open
Abstract
The aims of this observational “proof-of-concept” study were to analyze the clinical/psychological characteristics and gut microbiota/mycobiota composition of individuals with suspected non-celiac gluten/wheat sensitivity (NCGS/WS) according to responses to the double-blind-placebo-controlled (DBPC) crossover gluten challenge test. Fifty individuals with suspected NCGS/WS were subjected to the DBPC challenge test; anthropometric measurements, psychometric questionnaires, and fecal samples were collected. Twenty-seven (54%) participants were gluten responsive (NCGS), and 23 were placebo responsive, with an order effect. NCGS individuals displayed a significantly lower risk of eating disorders and a higher mental health score when compared to placebo-responsive participants, confirmed by multiple logistic regression analyses (OR = 0.87; 95% CI 0.76–0.98, p = 0.021, and OR = 1.30; 95% CI 1.06–1.59, p = 0.009, respectively). Principal coordinate analyses based on microbiota composition showed a separation by the DBPC response (p = 0.039). For Bacteroides (p = 0.05) and Parabacteroides (p = 0.007), the frequency of amplicon sequence variants was lower, and that for Blautia (p = 0.009) and Streptococcus (p = 0.004) was higher in NCGS individuals at multiple regression analyses. No difference in the mycobiota composition was detected between the groups. In conclusion, almost half of the individuals with suspected gluten sensitivity reported symptoms with placebo; they showed lower mental health scores, increased risk for eating disorders, and a different gut microbiota composition.
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Affiliation(s)
- Valentina Ponzo
- Department of Medical Sciences, University of Torino, 10126 Torino, Italy; (V.P.); (I.G.); (M.P.); (F.B.); (E.G.)
| | - Ilario Ferrocino
- Department of Agricultural, Forestry and Food Science, University of Torino, 10095 Torino, Italy; (M.R.C.); (L.C.)
- Correspondence: (I.F.); (S.B.); Tel.: +39-11-633-6036 (S.B.)
| | - Ilaria Goitre
- Department of Medical Sciences, University of Torino, 10126 Torino, Italy; (V.P.); (I.G.); (M.P.); (F.B.); (E.G.)
| | - Marianna Pellegrini
- Department of Medical Sciences, University of Torino, 10126 Torino, Italy; (V.P.); (I.G.); (M.P.); (F.B.); (E.G.)
| | - Mauro Bruno
- Gastroenterology and Digestive Endoscopy Unit, “Città della Salute e della Scienza” Hospital, 10126 Torino, Italy; (M.B.); (M.A.)
| | - Marco Astegiano
- Gastroenterology and Digestive Endoscopy Unit, “Città della Salute e della Scienza” Hospital, 10126 Torino, Italy; (M.B.); (M.A.)
| | - Gianni Cadario
- Allergology and Clinical Immunology Unit, “Città della Salute e della Scienza” Hospital, 10126 Torino, Italy;
| | - Eleonora Castellana
- Hospital Pharmacy, “Città della Salute e della Scienza” Hospital, 10126 Torino, Italy;
| | - Fabio Bioletto
- Department of Medical Sciences, University of Torino, 10126 Torino, Italy; (V.P.); (I.G.); (M.P.); (F.B.); (E.G.)
| | - Maria Rita Corvaglia
- Department of Agricultural, Forestry and Food Science, University of Torino, 10095 Torino, Italy; (M.R.C.); (L.C.)
| | | | - Luca Cocolin
- Department of Agricultural, Forestry and Food Science, University of Torino, 10095 Torino, Italy; (M.R.C.); (L.C.)
| | - Ezio Ghigo
- Department of Medical Sciences, University of Torino, 10126 Torino, Italy; (V.P.); (I.G.); (M.P.); (F.B.); (E.G.)
| | - Simona Bo
- Department of Medical Sciences, University of Torino, 10126 Torino, Italy; (V.P.); (I.G.); (M.P.); (F.B.); (E.G.)
- Correspondence: (I.F.); (S.B.); Tel.: +39-11-633-6036 (S.B.)
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Abstract
Irritable bowel syndrome (IBS) affects 10% to 15% of the population and often is difficult to treat with available pharmacologic agents. Dietary therapies for IBS are of particular interest because up to 90% of IBS patients exclude certain foods to improve their gastrointestinal symptoms. Among the available dietary interventions for IBS, the low FODMAP diet has the greatest evidence for efficacy. Although dietary therapies rapidly are becoming first-line treatment of IBS, gastroenterologists need to be aware of the negative effects of prescribing restrictive diets and red flag symptoms of maladaptive eating patterns.
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Suter DAI, Békés F. Who is to blame for the increasing prevalence of dietary sensitivity to wheat? CEREAL RESEARCH COMMUNICATIONS 2021; 49:1-19. [DOI: 10.1007/s42976-020-00114-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Indexed: 01/05/2025]
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Catassi GN, Naspi L, Catassi C. Non-Celiac Gluten Sensitivity. DIAGNOSIS AND MANAGEMENT OF GLUTEN-ASSOCIATED DISORDERS 2021:197-203. [DOI: 10.1007/978-3-030-56722-4_16] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Alaedini A. Molecular triggers of non-celiac wheat sensitivity. BIOTECHNOLOGICAL STRATEGIES FOR THE TREATMENT OF GLUTEN INTOLERANCE 2021:25-44. [DOI: 10.1016/b978-0-12-821594-4.00010-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Transeth EL, Dale HF, Lied GA. Comparison of gut microbiota profile in celiac disease, non-celiac gluten sensitivity and irritable bowel syndrome: A systematic review. TURKISH JOURNAL OF GASTROENTEROLOGY 2020; 31:735-745. [PMID: 33361035 DOI: 10.5152/tjg.2020.19551] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Gut microbiota is vital for human health. Shifts in the microbial diversity can affect bacterial function, and dysbiosis is associated with a variety of gastrointestinal disorders, including celiac disease (CD) and irritable bowel syndrome (IBS). The distinction between IBS and non-celiac gluten sensitivity (NCGS) is unclear, and it is conceivable that the gut microbiota profile of these patients may overlap. To our knowledge, no existing literature has evaluated the microbial characteristics in CD, IBS, and NCGS. Hence, this systematic review aims to compare the gut microbiota profile in these three diagnoses. A literature search was conducted in PubMed (Medline) until April 2019. Studies investigating bacterial diversity in the gut of patients with CD, IBS, and NCGS were eligible. Inclusion criteria were observational studies and randomized controlled trials reporting bacterial profile at baseline. Ninety-one articles were identified, of which 13 trials were eligible for inclusion. Overall, the bacterial composition of the gut microbiota of patients with CD and those with IBS shared the many similarities. The microbial richness was correspondingly reduced in these patient-groups compared with healthy controls, but this was not reported for NCGS. Our findings suggest that the bacterial profiles of patients with IBS and CD share certain disease-specific trends. Fewer similarities were observed between the bacterial profiles of patients with IBS and NCGS. Notably, the data are limited; thus, no solid conclusions can be made on the basis of these findings alone. The suggested trends can be a valuable basis for further research.
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Affiliation(s)
- Elin Lund Transeth
- Centre for Nutrition, Department of Clinical Medicine, University of Bergen, Bergen, Norway
| | - Hanna Fjeldheim Dale
- Centre for Nutrition, Department of Clinical Medicine, University of Bergen, Bergen, Norway;National Centre of Functional Gastrointestinal Disorders, Haukeland University Hospital, Bergen, Norway
| | - Gülen Arslan Lied
- Centre for Nutrition, Department of Clinical Medicine, University of Bergen, Bergen, Norway;National Centre of Functional Gastrointestinal Disorders, Haukeland University Hospital, Bergen, Norway
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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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Castillo-Rodal AI, Furuzawa-Carballeda J, Peláez-Luna M, Castro-Gómez J, López-Vidal Y, Uscanga L. More fuel to the fire: some patients with non-celiac self-reported wheat sensitivity exhibit adaptive immunological responses in duodenal mucosa. BMC Gastroenterol 2020; 20:414. [PMID: 33297984 PMCID: PMC7726874 DOI: 10.1186/s12876-020-01564-w] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2020] [Accepted: 11/30/2020] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND In contrast to the well-characterized Celiac Disease (CD), the clinical scenarios encompassed by the non-celiac self-reported wheat sensitivity (NCSRWS) might be related to different antigens that trigger distinct immune-inflammatory reactions. Although an increased number of intestinal intraepithelial lymphocytes is observed at the inception of both diseases, the subsequent immunopathogenic pathways seem to be different. We aimed to describe the cytokine profile observed in the duodenal mucosa of patients with NCSRWS. METHODS In a blind, cross-sectional study, we included duodenal biopsies from 15 consecutive untreated patients with active CD, 9 individuals with NCSRWS and 10 subjects with dyspepsia without CD and food intolerances. Immunohistochemistry and flow-cytometry were used to determine the presence of pro-inflammatory cytokine expressing monocytes and monocyte-derived dendritic cells involved in innate immune activation, cytokine-driven polarization and maintenance of Th1 and Th17/Th 22, and anti-inflammatory/profibrogenic cytokines. RESULTS The percentage of cells expressing all tested cytokines in the lamina propria and the epithelium was higher in CD patients than in the control group. Cytokines that induce and maintain Th1 and Th17 polarization were higher in CD than in NCSRWS and controls, also were higher in NCSRWS compared to controls. Similar differences were detected in the expression of IL-4 and TGF-1, while IL-10-expressing cells were lower in NCSRWS patients than in controls and CD subjects. CONCLUSIONS NCSRWS patients exhibit components of both, innate and adaptive immune mechanisms but to a lesser extent compared to CD.
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Affiliation(s)
- Antonia Isabel Castillo-Rodal
- Department of Microbiology and Parasitology, Facultad de Medicina, Universidad Nacional Autónoma de México, Alcaldía de Coyoacán, Mexico City, Mexico
| | - Janette Furuzawa-Carballeda
- Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, Alcaldía de Tlalpan, 14000, Mexico City, Mexico
| | - Mario Peláez-Luna
- Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, Alcaldía de Tlalpan, 14000, Mexico City, Mexico
| | - José Castro-Gómez
- Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, Alcaldía de Tlalpan, 14000, Mexico City, Mexico
| | - Yolanda López-Vidal
- Department of Microbiology and Parasitology, Facultad de Medicina, Universidad Nacional Autónoma de México, Alcaldía de Coyoacán, Mexico City, Mexico
| | - Luis Uscanga
- Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15, Alcaldía de Tlalpan, 14000, Mexico City, Mexico.
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Barbaro MR, Cremon C, Wrona D, Fuschi D, Marasco G, Stanghellini V, Barbara G. Non-Celiac Gluten Sensitivity in the Context of Functional Gastrointestinal Disorders. Nutrients 2020; 12:3735. [PMID: 33291590 PMCID: PMC7761787 DOI: 10.3390/nu12123735] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2020] [Revised: 11/27/2020] [Accepted: 12/01/2020] [Indexed: 02/07/2023] Open
Abstract
Gluten-free diets are increasingly chosen in the Western world, even in the absence of a diagnosis of celiac disease. Around 10% of people worldwide self-report gluten-related complaints, including intestinal and extra-intestinal symptoms. In most cases, these subjects would be labeled as patients suffering from irritable bowel syndrome (IBS) who place themselves on a gluten-free diet even in the absence of celiac disease. In some instances, patients report a clear benefit by avoiding gluten from their diet and/or symptom worsening upon gluten reintroduction. This clinical entity has been termed non-celiac gluten sensitivity (NCGS). The symptoms referred by these patients are both intestinal and extra-intestinal, suggesting that similarly to functional gastrointestinal disorders, NCGS is a disorder of gut-brain interaction. It remains unclear if gluten is the only wheat component involved in NCGS. The mechanisms underlying symptom generation in NCGS remain to be fully clarified, although in the past few years, the research has significantly moved forward with new data linking NCGS to changes in gut motility, permeability and innate immunity. The diagnosis is largely based on the self-reported reaction to gluten by the patient, as there are no available biomarkers, and confirmatory double-blind challenge protocols are unfeasible in daily clinical practice. Some studies suggest that a small proportion of patients with IBS have an intolerance to gluten. However, the benefits of gluten-free or low-gluten diets in non-celiac disease-related conditions are limited, and the long-term consequences of this practice may include nutritional and gut microbiota unbalance. Here, we summarize the role of gluten in the clinical features, pathophysiology, and management of NCGS and disorders of gut-brain interaction.
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Affiliation(s)
- Maria Raffaella Barbaro
- IRCCS S. Orsola, 40138 Bologna, Italy; (M.R.B.); (C.C.); (D.W.); (D.F.); (G.M.); (V.S.)
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy
| | - Cesare Cremon
- IRCCS S. Orsola, 40138 Bologna, Italy; (M.R.B.); (C.C.); (D.W.); (D.F.); (G.M.); (V.S.)
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy
| | - Diana Wrona
- IRCCS S. Orsola, 40138 Bologna, Italy; (M.R.B.); (C.C.); (D.W.); (D.F.); (G.M.); (V.S.)
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy
| | - Daniele Fuschi
- IRCCS S. Orsola, 40138 Bologna, Italy; (M.R.B.); (C.C.); (D.W.); (D.F.); (G.M.); (V.S.)
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy
| | - Giovanni Marasco
- IRCCS S. Orsola, 40138 Bologna, Italy; (M.R.B.); (C.C.); (D.W.); (D.F.); (G.M.); (V.S.)
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy
| | - Vincenzo Stanghellini
- IRCCS S. Orsola, 40138 Bologna, Italy; (M.R.B.); (C.C.); (D.W.); (D.F.); (G.M.); (V.S.)
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy
| | - Giovanni Barbara
- IRCCS S. Orsola, 40138 Bologna, Italy; (M.R.B.); (C.C.); (D.W.); (D.F.); (G.M.); (V.S.)
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy
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Koumbi L, Giouleme O, Vassilopoulou E. Non-Celiac Gluten Sensitivity and Irritable Bowel Disease: Looking for the Culprits. Curr Dev Nutr 2020; 4:nzaa176. [PMID: 33442571 PMCID: PMC7788486 DOI: 10.1093/cdn/nzaa176] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2020] [Revised: 11/02/2020] [Accepted: 12/02/2020] [Indexed: 12/13/2022] Open
Abstract
During the last 30 y, a gluten-free diet has been classified among the most popular fad diets mainly due to the ambiguous notion that gluten avoidance promotes health. Gluten intolerance has been implicated in non-celiac gluten sensitivity (NCGS) and irritable bowel syndrome (IBS), 2 disorders with overlapping symptoms and increasing trend. Together with gluten, other wheat components; fermentable oligo-, di-, monosaccharide, and polyols (FODMAPs); and amylase trypsin inhibitors (ATIs), are implicated in the pathogenesis of both disorders. Gut microflora alterations in IBS and NCGS have been described, while microbiota manipulations have been shown to be promising in some IBS cases. This literature review summarizes our current knowledge on the impact of wheat ingredients (gluten, FODMAPs, and ATIs) in IBS and NCGS. In both disorders, FODMAPs and ATIs trigger gut dysbiosis, suggesting that gluten may not be the culprit, and microbiota manipulations can be applied in diagnostic and intervention approaches.
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Affiliation(s)
- Lemonica Koumbi
- Department of Nutritional Sciences and Dietetics, International Hellenic University (IHU), Thessaloniki, Greece
| | - Olga Giouleme
- Medical School, Aristotle University, Thessaloniki, Greece
| | - Emilia Vassilopoulou
- Department of Nutritional Sciences and Dietetics, International Hellenic University (IHU), Thessaloniki, Greece
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Low Fermentable Oligo- Di- and Mono-Saccharides and Polyols (FODMAPs) or Gluten Free Diet: What Is Best for Irritable Bowel Syndrome? Nutrients 2020; 12:nu12113368. [PMID: 33139629 PMCID: PMC7692077 DOI: 10.3390/nu12113368] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Revised: 10/22/2020] [Accepted: 10/29/2020] [Indexed: 02/07/2023] Open
Abstract
Irritable Bowel Syndrome (IBS) is a very common functional gastrointestinal disease. Its pathogenesis is multifactorial and not yet clearly defined, and hence, its therapy mainly relies on symptomatic treatments. Changes in lifestyle and dietary behavior are usually the first step, but unfortunately, there is little high-quality scientific evidence regarding a dietary approach. This is due to the difficulty in setting up randomized double-blind controlled trials which objectively evaluate efficacy without the risk of a placebo effect. However, a Low Fermentable Oligo-, Di- and Mono-saccharides And Polyols (FODMAP) Diet (LFD) and Gluten Free Diet (GFD) are among the most frequently suggested diets. This paper aims to evaluate their possible role in IBS management. A GFD is less restrictive and easier to implement in everyday life and can be suggested for patients who clearly recognize gluten as a trigger of their symptoms. An LFD, being more restrictive and less easy to learn and to follow, needs the close supervision of a skilled nutritionist and should be reserved for patients who recognize that the trigger of their symptoms is not, or not only, gluten. Even if the evidence is of very low-quality for both diets, the LFD is the most effective among the dietary interventions suggested for treating IBS, and it is included in the most updated guidelines.
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Di Liberto D, Carlisi D, D’Anneo A, Emanuele S, Giuliano M, De Blasio A, Calvaruso G, Lauricella M. Gluten Free Diet for the Management of Non Celiac Diseases: The Two Sides of the Coin. Healthcare (Basel) 2020; 8:healthcare8040400. [PMID: 33066519 PMCID: PMC7712796 DOI: 10.3390/healthcare8040400] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2020] [Revised: 10/07/2020] [Accepted: 10/09/2020] [Indexed: 12/12/2022] Open
Abstract
A lifelong adherence to a gluten-free (GF) diet is currently the only treatment for Celiac disease (CD), an autoimmune disorder that arises after gluten ingestion in individuals who are genetically predisposed. The gluten intake exerts toxic effects through several pathways involving gut barrier integrity, intestinal microbiota composition and immune system stimulation. However, despite the great benefit of GF diet for CD patients, its use has been debated. Indeed, individuals who adopt this diet regime may be at risk of nutrient deficiencies. Emerging evidence supports a beneficial effect of a GF diet also for other pathological conditions, including gluten-related disorders (GRD) often associated to CD, such as Non celiac gluten sensitivity (NCGS) and Dermatitis Herpetiforme (DH) as well as Irritable bowel syndrome (IBS) and Diabetes. This suggests a pathogenic role of gluten in these conditions. Despite the growing popularity of GF diet among consumers, to date, there are limited evidences supporting its use for the management of non-celiac diseases. Therefore, in this review, we discuss whether the GF diet could really improve the general quality of life of patients with GRD and non-GRD conditions, keeping in mind its sensorial limitations and nutritional inadequacies. In addition, we discuss the current motivations, leading to the use of a GF diet, despite the inferior quality of GF products respect to those containing gluten.
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Affiliation(s)
- Diana Di Liberto
- Department of Biomedicine, Neurosciences and Advanced Diagnostics (BIND), CLADIBIOR, University of Palermo, 90127 Palermo, Italy
- Correspondence: (D.D.L.); (A.D.); Tel.: +39-09123865854 (D.D.L.); +39-09123890650 (A.D.)
| | - Daniela Carlisi
- Department of Biomedicine, Neurosciences and Advanced Diagnostics (BIND), Institute of Biochemistry, University of Palermo, 90127 Palermo, Italy; (D.C.); (S.E.); (M.L.)
| | - Antonella D’Anneo
- Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), Laboratory of Biochemistry, University of Palermo, 90127 Palermo, Italy; (M.G.); (A.D.B.); (G.C.)
- Correspondence: (D.D.L.); (A.D.); Tel.: +39-09123865854 (D.D.L.); +39-09123890650 (A.D.)
| | - Sonia Emanuele
- Department of Biomedicine, Neurosciences and Advanced Diagnostics (BIND), Institute of Biochemistry, University of Palermo, 90127 Palermo, Italy; (D.C.); (S.E.); (M.L.)
| | - Michela Giuliano
- Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), Laboratory of Biochemistry, University of Palermo, 90127 Palermo, Italy; (M.G.); (A.D.B.); (G.C.)
| | - Anna De Blasio
- Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), Laboratory of Biochemistry, University of Palermo, 90127 Palermo, Italy; (M.G.); (A.D.B.); (G.C.)
| | - Giuseppe Calvaruso
- Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), Laboratory of Biochemistry, University of Palermo, 90127 Palermo, Italy; (M.G.); (A.D.B.); (G.C.)
| | - Marianna Lauricella
- Department of Biomedicine, Neurosciences and Advanced Diagnostics (BIND), Institute of Biochemistry, University of Palermo, 90127 Palermo, Italy; (D.C.); (S.E.); (M.L.)
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Demirkesen I, Ozkaya B. Recent strategies for tackling the problems in gluten-free diet and products. Crit Rev Food Sci Nutr 2020; 62:571-597. [DOI: 10.1080/10408398.2020.1823814] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- Ilkem Demirkesen
- Department of Animal Health, Food and Feed Research, General Directorate of Agricultural Research and Policies, Ministry of Agriculture and Forestry, Ankara, Turkey
| | - Berrin Ozkaya
- Department of Food Engineering, Ankara University, Ankara, Turkey
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Serena G, D'Avino P, Fasano A. Celiac Disease and Non-celiac Wheat Sensitivity: State of Art of Non-dietary Therapies. Front Nutr 2020; 7:152. [PMID: 33015123 PMCID: PMC7506149 DOI: 10.3389/fnut.2020.00152] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Accepted: 07/28/2020] [Indexed: 12/12/2022] Open
Abstract
Gluten related disorders (GRD), which include celiac disease, non-celiac wheat sensitivity and wheat allergy are heterogeneous conditions triggered by ingestion of gluten-containing grains. Together, their prevalence is estimated to be ~5% in the general population, however, in the last years the number of diagnoses has been rapidly increasing. To this day, the gold standard treatment for these disorders is the complete removal of gluten-containing grains from the diet. Although this therapy results effective in the majority of patients, up to 30% of individuals affected by GRD continue to present persistent symptoms. In addition, gluten-free diet has been shown to have poor nutritional quality and to cause a socio-economic burden in patients' quality of life. In order to respond to these issues, the scientific community has been focusing on finding additional and adjuvant non-dietary therapies. In this review, we focus on two main gluten related disorders, celiac disease and non-celiac wheat sensitivity. We delineate the actual knowledge about potential treatments and their relative efficacy in pre-clinical and clinical trials.
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Affiliation(s)
- Gloria Serena
- Division of Pediatric Gastroenterology and Nutrition, Center for Celiac Research, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA, United States
| | - Paolo D'Avino
- Division of Pediatric Gastroenterology and Nutrition, Center for Celiac Research, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA, United States.,Vita-Salute San Raffaele University, Milan, Italy
| | - Alessio Fasano
- Division of Pediatric Gastroenterology and Nutrition, Center for Celiac Research, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA, United States.,European Biomedical Research Institute of Salerno (EBRIS), Salerno, Italy
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Taraghikhah N, Ashtari S, Asri N, Shahbazkhani B, Al-Dulaimi D, Rostami-Nejad M, Rezaei-Tavirani M, Razzaghi MR, Zali MR. An updated overview of spectrum of gluten-related disorders: clinical and diagnostic aspects. BMC Gastroenterol 2020; 20:258. [PMID: 32762724 PMCID: PMC7409416 DOI: 10.1186/s12876-020-01390-0] [Citation(s) in RCA: 69] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2020] [Accepted: 07/21/2020] [Indexed: 02/06/2023] Open
Abstract
The incidence of gluten-related disorders (GRDs) continues to increase and its global prevalence is estimated at approximately 5% of the population. Celiac disease (CD), dermatitis herpetiformis (DH), gluten ataxia (GA), wheat allergy (WA), and non-celiac gluten sensitivity (NCGS) are the five major GRDs that present with a wide range of clinical manifestations. The diagnosis of GRDs can be challenging because the typical and atypical clinical manifestations of the GRDs overlap. In this review, the current definitions of gluten-related disorders, focusing on their clinical features, diagnostic and therapeutic approaches are presented. We concluded that GRDs are usually diagnosed using a combination of clinical features, serological tests, and histopathological findings. Treatment usually involves dietary modification.
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Affiliation(s)
- Nazanin Taraghikhah
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sara Ashtari
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Nastaran Asri
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Bijan Shahbazkhani
- Division of Gastroenterology and Liver Diseases, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - David Al-Dulaimi
- Department of Gastroenterology, South Warwickshire Foundation Trust, Warwickshire, UK
| | - Mohammad Rostami-Nejad
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Mostafa Rezaei-Tavirani
- Proteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Razzaghi
- Laser Application in Medical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Khan A, Suarez MG, Murray JA. Nonceliac Gluten and Wheat Sensitivity. Clin Gastroenterol Hepatol 2020; 18:1913-1922.e1. [PMID: 30978535 DOI: 10.1016/j.cgh.2019.04.009] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2018] [Revised: 03/21/2019] [Accepted: 04/03/2019] [Indexed: 02/07/2023]
Abstract
Non-celiac gluten and/or wheat sensitivity (NCGS) is thought to be an immune-mediated reaction to gluten or other components of wheat (eg, fructans or amylase trypsin inhibitors) with intestinal and extraintestinal symptoms which improve once gluten and/or wheat is eliminated from the diet and after a diagnosis of celiac disease and wheat allergy have been excluded with appropriate testing. However, there is a great deal of skepticism within the scientific community questioning the existence of NCGS as a distinct clinical disorder. There are no strict diagnostic criteria and a placebo-controlled rechallenge trial has been recommended for diagnosis. In research settings, a double-blind placebo-controlled rechallenge trial has been recommended for diagnosis. There are limited studies estimating the prevalence of NCGS using this study design. The existing studies have variable results likely due to the lack of a uniform diagnostic criterion, a great deal of dependence on the patient's perception of symptoms and a large nocebo effect in existing studies. In clinical practice, a single blind placebo-controlled rechallenge trial has been recommended for diagnosis. The pathogenesis of NCGS is unclear and there is no known biomarker or diagnostic histologic lesion for this condition. It is important to adopt a multidisciplinary team approach to patients with suspected NCGS with involvement of the primary care doctor, gastroenterologist, pathologist and nutritionist who may play an important role in diagnosis and treatment. There may especially be a role in elimination of food containing high quantity of both gluten and fructans. Furthermore, patients should be educated on the nutritional implications of consuming a long-term gluten-free diet.
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Affiliation(s)
- Anam Khan
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas.
| | - Milena Gould Suarez
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas
| | - Joseph A Murray
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
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Efthymakis K, Clemente E, Marchioni M, Di Nicola M, Neri M, Sallese M. An Exploratory Gene Expression Study of the Intestinal Mucosa of Patients with Non-Celiac Wheat Sensitivity. Int J Mol Sci 2020; 21:ijms21061969. [PMID: 32183058 PMCID: PMC7139384 DOI: 10.3390/ijms21061969] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Revised: 03/06/2020] [Accepted: 03/11/2020] [Indexed: 12/12/2022] Open
Abstract
Non-celiac wheat sensitivity (NCWS) is a recently recognized syndrome triggered by a gluten-containing diet. The pathophysiological mechanisms engaged in NCWS are poorly understood and, in the absence of laboratory markers, the diagnosis relies only on a double-blind protocol of symptoms evaluation during a gluten challenge. We aimed to shed light on the molecular mechanisms governing this disorder and identify biomarkers helpful to the diagnosis. By a genome-wide transcriptomic analysis, we investigated gene expression profiles of the intestinal mucosa of 12 NCWS patients, as well as 7 controls. We identified 300 RNA transcripts whose expression differed between NCWS patients and controls. Only 37% of these transcripts were protein-coding RNA, whereas the remaining were non-coding RNA. Principal component analysis (PCA) and receiver operating characteristic curves showed that these microarray data are potentially useful to set apart NCWS from controls. Literature and network analyses indicated a possible implication/dysregulation of innate immune response, hedgehog pathway, and circadian rhythm in NCWS. This exploratory study indicates that NCWS can be genetically defined and gene expression profiling might be a suitable tool to support the diagnosis. The dysregulated genes suggest that NCWS may result from a deranged immune response. Furthermore, non-coding RNA might play an important role in the pathogenesis of NCWS.
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Affiliation(s)
- Konstantinos Efthymakis
- Department of Medicine and Ageing Sciences, ‘G. d’Annunzio’ University of Chieti–Pescara, 66100 Chieti, Italy;
- Center for Advanced Studies and Technology (CAST), ‘G. d’Annunzio’ University of Chieti-Pescara, 66100 Chieti, Italy;
| | - Emanuela Clemente
- Center for Advanced Studies and Technology (CAST), ‘G. d’Annunzio’ University of Chieti-Pescara, 66100 Chieti, Italy;
- Department of Medical, Oral and Biotechnological Sciences, ‘G. d’Annunzio’ University of Chieti–Pescara, 66100 Chieti, Italy; (M.M.); (M.D.N.)
| | - Michele Marchioni
- Department of Medical, Oral and Biotechnological Sciences, ‘G. d’Annunzio’ University of Chieti–Pescara, 66100 Chieti, Italy; (M.M.); (M.D.N.)
| | - Marta Di Nicola
- Department of Medical, Oral and Biotechnological Sciences, ‘G. d’Annunzio’ University of Chieti–Pescara, 66100 Chieti, Italy; (M.M.); (M.D.N.)
| | - Matteo Neri
- Department of Medicine and Ageing Sciences, ‘G. d’Annunzio’ University of Chieti–Pescara, 66100 Chieti, Italy;
- Center for Advanced Studies and Technology (CAST), ‘G. d’Annunzio’ University of Chieti-Pescara, 66100 Chieti, Italy;
- Correspondence: (M.N.); (M.S.)
| | - Michele Sallese
- Center for Advanced Studies and Technology (CAST), ‘G. d’Annunzio’ University of Chieti-Pescara, 66100 Chieti, Italy;
- Department of Medical, Oral and Biotechnological Sciences, ‘G. d’Annunzio’ University of Chieti–Pescara, 66100 Chieti, Italy; (M.M.); (M.D.N.)
- Correspondence: (M.N.); (M.S.)
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