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How to manage celiac disease and gluten-free diet during the COVID-19 era: proposals from a tertiary referral center in a high-incidence scenario.
Elli, L, Barisani, D, Vaira, V, Bardella, MT, Topa, M, Vecchi, M, Doneda, L, Scricciolo, A, Lombardo, V, Roncoroni, L
BMC gastroenterology. 2020;(1):387
Abstract
The outbreak of COVID-19 and SARS-CoV-2 infection is spreading worldwide as the first coronavirus pandemic. The clinical picture is variable but flu-like symptoms are common with bilateral interstitial pneumonia being the most frightening presentation. No specific therapies nor vaccine have been developed to date and the only way to limit the virus diffusion is by modifying one's lifestyle limiting social life and following strict hygienic precautions. No data is available on the risk of COVID-19 and its outcomes in celiac disease (CeD). The restrictions applied to counter COVID-19 can impact on CeD treatment and gluten-free dieting, the only available therapy for CeD. With the present manuscript, we aim to support gastroenterologists and nutritionists in the management of CeD patients in the new pandemic scenario, being conscious that availability and local situations are extremely various.
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Correction: Roncoroni, L. et al. A Low FODMAP Gluten-Free Diet Improves Functional Gastrointestinal Disorders and Overall Mental Health of Celiac Disease Patients: A Randomized Controlled Trial. Nutrients 2018, 10, 1023.
Roncoroni, L, Bascuñán, KA, Doneda, L, Scricciolo, A, Lombardo, V, Branchi, F, Ferretti, F, Dell'Osso, B, Montanari, V, Bardella, MT, et al
Nutrients. 2019;(3)
Abstract
The authors have requested that the following changes be made to their paper [...].
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Exposure to Different Amounts of Dietary Gluten in Patients with Non-Celiac Gluten Sensitivity (NCGS): An Exploratory Study.
Roncoroni, L, Bascuñán, KA, Vecchi, M, Doneda, L, Bardella, MT, Lombardo, V, Scricciolo, A, Branchi, F, Elli, L
Nutrients. 2019;11(1)
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Non-coeliac gluten sensitivity (NCGS) is characterised by adverse gastrointestinal symptoms related to ingestion of gluten-containing foods and amelioration of symptoms when gluten is removed from the diet. It is currently unclear whether gluten sensitivity is a permanent condition. The aim of this exploratory study was to evaluate the effects of gluten re-introduction in 22 NCGS patients who have been on a strict gluten-free diet for three weeks. Working with a qualified nutritionist, participants began incrementally introducing gluten each week for three weeks. Gastrointestinal symptoms and quality of life were assessed at baseline and post-intervention. When adverse symptomology was reported, participants returned to the gluten-level before symptoms started. This study found mixed results with gluten reintroduction. Of the 22 participants, 8 were able to return to a normal gluten-containing diet, and the remaining participants had differing levels of tolerance for gluten consumption. Based on these results, the authors conclude further controlled studies are required to assess the clinical response of reintroducing dietary gluten in patients with NCGS.
Abstract
It is unclear whether patients with non-celiac gluten sensitivity (NCGS) can tolerate gluten. We have evaluated the changes of both gastrointestinal symptoms and quality of life for NCGS patients after the re-introduction of dietary gluten. Twenty-two NCGS patients reporting functional gastroenterological symptoms and on gluten-free diet (GFD) for the previous three weeks were exposed to incremental gluten-containing diets. Three groups were compared at baseline (immediately after 3-weeks on GFD) and immediately after the return of symptomatology: (i) a group tolerating a low-gluten diet (3.5 g gluten/day, week 1, n = 8), (ii) a group tolerating a mid-gluten diet (8 g gluten/day, week 2, n = 6), and (iii) a group tolerating a high-gluten diet (13 g gluten/day, week 3, n = 8). Their gastrointestinal symptoms and quality of life were assessed at baseline and post-intervention. The most common symptoms were: constipation (46%), abdominal pain (50%) and dyspepsia (38%). A decrease in several short form health survey (SF-36) sub-scores (all p < 0.03) after gluten re-introduction was only observed in the group tolerating the low-gluten diet; the same group showed a lower post-intervention role-emotional SF-36 score (p = 0.01). Most gastrointestinal symptoms remained similar after gluten re-introduction. However, a decrease in the general perception of well-being was only found after gluten re-introduction in the group tolerating a low-gluten diet (p = 0.01); the same was true when comparing the post-intervention general well-being perception among the three groups (p = 0.050). In conclusion, dissimilar responses from patients with NCGS were observed after the re-introduction of gluten, with gluten at a low dosage affecting the quality of life and general well-being of a group of patients, whereas others tolerate even higher doses of dietary gluten.
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A Low FODMAP Gluten-Free Diet Improves Functional Gastrointestinal Disorders and Overall Mental Health of Celiac Disease Patients: A Randomized Controlled Trial.
Roncoroni, L, Bascuñán, KA, Doneda, L, Scricciolo, A, Lombardo, V, Branchi, F, Ferretti, F, Dell'Osso, B, Montanari, V, Bardella, MT, et al
Nutrients. 2018;10(8)
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Plain language summary
Coeliac disease (CD) is an autoimmune disorder in which gluten ingestion induces inflammation in the small intestines. While a gluten-free diet (GFD) alleviates gastrointestinal (GI) symptoms in the majority of CD patients, there is a subset of patients following a strict GFD that still experience GI symptoms. The aim of this study is to determine if a low fermentable, oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet would help reduce persistent symptoms in 44 CD patients following a strict GFD. Participants were randomised to receive a structured 21-day dietary plan of either a low-FODMAP GFD or a high-FODMAP GFD and were evaluated for GI symptoms, psychological wellbeing and quality of life at baseline and the end of the intervention. This study found quality of life and abdominal pain improved significantly in the low-FODMAP group compared to the high-FODMAP group. Based on these findings, the authors conclude a short-term low-FODMAP diet helps to improve persistent GI symptoms and enhance general wellbeing in this subgroup of CD patients. Further evaluation is recommended to better understand the long-term clinical effects of FODMAPs in CD patients.
Abstract
A subset of patients with celiac disease (CD) on a gluten-free diet (GFD) reported the persistence of functional gastrointestinal disorders. Foods containing fermentable, oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) can trigger a broad range of gastrointestinal symptoms in sensitive individuals. We evaluated the effects of a low FODMAP diet (LFD) on gastrointestinal and psychological symptomatology in CD patients. A total of 50 celiac patients on GFDs and with persistence of gastrointestinal symptoms were included. The patients were randomly allocated to one of two dietary groups-one on a low FODMAP GFD (LF-GFD, n = 25) and the other on a regular GFD (R-GFD, n = 25)-for 21 days. Psychological symptomatology and quality of life were evaluated by the Symptom Checklist-90-R (SCL-90) and the Short Form (36) Health Survey (SF-36) questionnaires, respectively. Gastrointestinal symptomatology and general well-being were evaluated by visual analogue scale (VAS) scores. After 21 days, 21 and 23 patients completed the dietary treatment on LF-GFD and R-GFD, respectively. A reduced global SCL-90 index (p < 0.0003) was found in the LF-GFD group but not in the R-GFD one. However, the SF-36 scores did not differ between groups after treatment. The VAS for abdominal pain was much lower, and the VAS for fecal consistency enhanced after treatment in the LF-GFD group. General well-being increased in both groups but with a much higher improvement in the LF-GFD (p = 0.03). A short-term LFD regimen helps to improve the psychological health and gastrointestinal symptomatology with enhanced well-being of CD patients with persisting functional gastrointestinal symptomatology. The long-term clinical effects of LFD in particular subgroups of CD patients need further evaluation.
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Evidence for the Presence of Non-Celiac Gluten Sensitivity in Patients with Functional Gastrointestinal Symptoms: Results from a Multicenter Randomized Double-Blind Placebo-Controlled Gluten Challenge.
Elli, L, Tomba, C, Branchi, F, Roncoroni, L, Lombardo, V, Bardella, MT, Ferretti, F, Conte, D, Valiante, F, Fini, L, et al
Nutrients. 2016;(2):84
Abstract
Non-celiac gluten sensitivity (NCGS) is characterized by the onset of symptoms after eating gluten-containing food. We aimed to single out NCGS subjects among subjects with functional gastrointestinal symptoms. Patients were enrolled in a multicenter double-blind placebo-controlled trial with crossover. Symptoms and quality of life were evaluated by means of 10-cm VAS and SF36. Iron parameters, transaminases and C reactive protein (CRP) were evaluated. After a three-week-long gluten-free diet (GFD), responsive patients were randomly assigned to gluten intake (5.6 g/day) or placebo for seven days, followed by crossover. The primary endpoint was the worsening of symptoms (VAS increase ≥3 cm) during gluten ingestion compared to placebo. One hundred and forty patients were enrolled and 134 (17 males, mean age 39.1 ± 11.7 years, BMI 22.4 ± 3.8) completed the first period. A total of 101 subjects (10 males, mean age 39.3 ± 11.0 years, BMI 22.3 ± 4.0) reported a symptomatic improvement (VAS score 2.3 ± 1.2 vs. 6.5 ± 2.2 before and after GFD, p = 0.001). 98 patients underwent the gluten challenge and 28 (all females, mean age 38.9 ± 12.7 years, BMI 22.0 ± 2.9) reported a symptomatic relapse and deterioration of quality of life. No parameters were found to be statistically associated with positivity to the challenge. However, 14 patients responded to the placebo ingestion. Taking into account this finding, about 14% of patients responding to gluten withdrawal showed a symptomatic relapse during the gluten challenge. This group is suspected to have NCGS.
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Non Celiac Gluten Sensitivity.
Bardella, MT, Elli, L, Ferretti, F
Current gastroenterology reports. 2016;(12):63
Abstract
PURPOSE OF REVIEW A new syndrome responding to gluten-free diet and defined non-celiac gluten sensitivity entered the spectrum of gluten-related disorders, together with celiac disease and wheat allergy. However, its definition, prevalence, diagnosis, pathogenesis, treatment, and follow up are still controversial. The purpose of the review is to summarize the evidence and problems emerging from the current literature. RECENT FINDINGS Direct implication of gluten in the onset of symptoms is often unproved as a low fermentable oligo-, di- and mono-saccharides and polyols diet or other components of cereals as wheat amylase trypsin inhibitor could be similarly involved. To date, no specific biomarkers or histological abnormalities confirm diagnosis, and only the self-reported response to gluten-free diet as well as a positive double blind placebo-gluten challenge characterizes these non-celiac, non-wheat allergic patients. Critical revision of published studies can offer practical indications in approaching this clinical topic and useful suggestions to standardize scientific researches.
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Diagnosis of gluten related disorders: Celiac disease, wheat allergy and non-celiac gluten sensitivity.
Elli, L, Branchi, F, Tomba, C, Villalta, D, Norsa, L, Ferretti, F, Roncoroni, L, Bardella, MT
World journal of gastroenterology. 2015;(23):7110-9
Abstract
Cereal crops and cereal consumption have had a vital role in Mankind's history. In the recent years gluten ingestion has been linked with a range of clinical disorders. Gluten-related disorders have gradually emerged as an epidemiologically relevant phenomenon with an estimated global prevalence around 5%. Celiac disease, wheat allergy and non-celiac gluten sensitivity represent different gluten-related disorders. Similar clinical manifestations can be observed in these disorders, yet there are peculiar pathogenetic pathways involved in their development. Celiac disease and wheat allergy have been extensively studied, while non-celiac gluten sensitivity is a relatively novel clinical entity, believed to be closely related to other gastrointestinal functional syndromes. The diagnosis of celiac disease and wheat allergy is based on a combination of findings from the patient's clinical history and specific tests, including serology and duodenal biopsies in case of celiac disease, or laboratory and functional assays for wheat allergy. On the other hand, non-celiac gluten sensitivity is still mainly a diagnosis of exclusion, in the absence of clear-cut diagnostic criteria. A multimodal pragmatic approach combining findings from the clinical history, symptoms, serological and histological tests is required in order to reach an accurate diagnosis. A thorough knowledge of the differences and overlap in clinical presentation among gluten-related disorders, and between them and other gastrointestinal disorders, will help clinicians in the process of differential diagnosis.
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Non-celiac gluten sensitivity: Time for sifting the grain.
Elli, L, Roncoroni, L, Bardella, MT
World journal of gastroenterology. 2015;(27):8221-6
Abstract
In the last few years, a new nomenclature has been proposed for the disease induced by the ingestion of gluten, a protein present in wheat, rice, barley and oats. Besides celiac disease and wheat allergy, the most studied forms of gluten-related disorders characterized by an evident immune mechanism (autoimmune in celiac disease and IgE-mediated in wheat allergy), a new entity has been included, apparently not driven by an aberrant immune response: the non-celiac gluten sensitivity (NCGS). NCGS is characterized by a heterogeneous clinical picture with intestinal and extraintestinal symptoms arising after gluten ingestion and rapidly improving after its withdrawal from the diet. The pathogenesis of NCGS is largely unknown, but a mixture of factors such as the stimulation of the innate immune system, the direct cytotoxic effects of gluten, and probably the synergy with other wheat molecules, are clues for the complicated puzzle. In addition, the diagnostic procedures still remain problematic due to the absence of efficient diagnostic markers; thus, diagnosis is based upon the symptomatic response to a gluten-free diet and the recurrence of symptoms after gluten reintroduction with the possibility of an important involvement of a placebo effect. The temporary withdrawal of gluten seems a reasonable therapy, but the timing of gluten reintroduction and the correct patient management approach are have not yet been determined.
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Transient elastography in patients with celiac disease: a noninvasive method to detect liver involvement associated with celiac disease.
Massironi, S, Rossi, RE, Fraquelli, M, Bardella, MT, Elli, L, Maggioni, M, Della Valle, S, Spampatti, MP, Colombo, M, Conte, D
Scandinavian journal of gastroenterology. 2012;(6):640-8
Abstract
BACKGROUND Liver involvement in celiac disease (CD) is clinically relevant and could require specific treatment in addition to gluten-free diet (GFD). Transient elastography (TE), a noninvasive tool for assessing liver stiffness (LS), has widely been reported as an accurate surrogate marker of liver fibrosis. AIMS To prospectively identify celiac patients with liver involvement by TE and to assess the effect of GFD. MATERIAL AND METHODS Ninety-five histologically confirmed CD patients (24 newly diagnosed) were consecutively evaluated by TE and compared with 146 patients with chronic hepatitis C (HCV) and 54 healthy subjects. RESULTS LS ranged between 2.8 and 6.7 kPa (median 4.9) in healthy subjects, defining 6.9 kPa as the upper reference limit (2 SD above the mean levels). TE was above 6.9 kPa in 10 (10.5%) CD patients. Median TE values resulted significantly higher in CD patients with hypertransaminasemia than those without [6.1 vs. 4.2 kPa (p < 0.01)]. Among the 24 newly diagnosed patients with CD, median TE values declined from 4.4 to 4 kPa, after 6 months of GFD, resulting below 6.9 kPa in 100% of the patients. CONCLUSIONS A subset of CD patients with hypertransaminasemia showed liver involvement by TE. Accordingly, based on its accuracy in predicting liver fibrosis, TE could be used to identify those CD patients suitable for liver biopsy.
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Transglutaminases in inflammation and fibrosis of the gastrointestinal tract and the liver.
Elli, L, Bergamini, CM, Bardella, MT, Schuppan, D
Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. 2009;(8):541-50
Abstract
Transglutaminases are a family of eight currently known calcium-dependent enzymes that catalyze the cross-linking or deamidation of proteins. They are involved in important biological processes such as wound healing, tissue repair, fibrogenesis, apoptosis, inflammation and cell-cycle control. Therefore, they play important roles in the pathomechanisms of autoimmune, inflammatory and degenerative diseases, many of which affect the gastrointestinal system. Transglutaminase 2 is prominent, since it is central to the pathogenesis of celiac disease, and modulates inflammation and fibrosis in inflammatory bowel and chronic liver diseases. This review highlights our present understanding of transglutaminase function in gastrointestinal and liver diseases and therapeutic strategies that target transglutaminase activities.