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Healthy and pro-inflammatory gut ecology plays a crucial role in the digestion and tolerance of a novel Gluten Friendly™ bread in celiac subjects: a randomized, double blind, placebo control in vivo study.
Andriulli, A, Bevilacqua, A, Palmieri, O, Latiano, A, Fontana, R, Gioffreda, D, Castellana, S, Mazza, T, Panza, A, Menzaghi, C, et al
Food & function. 2022;(3):1299-1315
Abstract
Gluten Friendly™ (GF) is a new gluten achieved through a physicochemical process applied to wheat kernels. The goal of this research was to assess the in vivo effects of Gluten Friendly™ bread on celiac gut mucosa and microbiota. In a double-blind placebo-controlled intervention study, 48 celiac disease (CD) patients were randomized into 3 groups to eat 100 g of bread daily, containing different doses (0; 3 g; 6 g) of GF for 12 weeks. The small-bowel morphology (VH/CrD), intraepithelial densities of CD3+, celiac serology, MUC2, CB1, gut permeability, proinflammatory cytokines, gluten in stools, symptoms, and gut microbial composition were assessed. All 48 CD subjects experienced no symptoms. K-means analysis evidenced celiac subjects clustering around unknown parameters independent of GF dosage: K1 35%; K2 30%; K3 35%. VH/CrD significantly decreased in K1 and K2. VH/CrD did not correlate with IEL increase in K2. 33-mer was not detected in 47% and 73% of patients in both K1 and K2, respectively. VH/CrD and IEL did not change significantly and strongly correlated with the absence of 33-mer in K3. Inflammation and VH/CrD decrease are strongly related with the presence of proinflammatory species at the baseline. A boost in probiotic, butyrate-producing genera, is strongly related with GF tolerance at the end of the trial. Our research suggests that a healthy and proinflammatory ecology could play a crucial role in the digestion and tolerance of the new gluten molecule in celiac subjects. However, GF can be completely digested by gut microbiota of CD subjects and shapes it toward gut homeostasis by boosting healthy butyrate-producing populations. The clinical trial registry number is NCT03137862 (https://clinicaltrials.gov).
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Feasibility and effects on the gut microbiota of a 12-week high-intensity interval training plus lifestyle education intervention on inactive adults with celiac disease.
Warbeck, C, Dowd, AJ, Kronlund, L, Parmar, C, Daun, JT, Wytsma-Fisher, K, Millet, GY, Schick, A, Reimer, RA, Fung, T, et al
Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme. 2021;(4):325-336
Abstract
This study assessed the feasibility and benefits of high-intensity interval training (HIIT) plus lifestyle education among inactive adults with celiac disease. Forty-one participants were randomized to receive the intervention (HIIT plus lifestyle education; HIIT+) for 12 weeks or waitlist control (WLC). Testing was completed at baseline, immediately post-intervention, and 3 months post-intervention. Generalized estimating equations were used to assess changes in the outcome variables over time between the groups. Mean percent of age-predicted maximum heart rate was 97.9% and average rating of perceived exertion was 6.33 (out of 10) during HIIT intervals. Following the intervention, the HIIT+ showed enrichment in relative abundance of Parabacteroides and Defluviitaleaceae_UCG_011 while WLC showed enrichment in relative abundance of Roseburia intestinalis, Klebsiella, and Adlercreutzia. A unique set of taxa were differentially abundant between the groups at 3 months post-intervention. HIIT+ participants experienced a reduction in resting heart rate (-6.6 bpm) immediately post-intervention compared with WLC. Further research is needed to establish an optimal HIIT protocol that may improve maximal oxygen uptake and metabolic syndrome biomarkers. Findings from this pilot study provide preliminary evidence that an HIIT intervention is feasible for inactive adults with celiac disease and leads to favourable changes in resting heart rate alongside potentially beneficial shifts in gut microbiota. Trial registration number: ClinicalTrials.gov number NCT03520244. Novelty: HIIT leads to potentially beneficial changes in the gut microbiota of adults with celiac disease. An HIIT exercise intervention is feasible and well tolerated for patients with celiac disease.
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Dietary and symptom assessment in adults with self-reported non-coeliac gluten sensitivity.
Skodje, GI, Minelle, IH, Rolfsen, KL, Iacovou, M, Lundin, KEA, Veierød, MB, Henriksen, C
Clinical nutrition ESPEN. 2019;:88-94
Abstract
BACKGROUND & AIMS The mechanisms behind non-coeliac gluten sensitivity (NCGS) are not fully understood although clinical symptoms have shown to subside after wheat withdrawal. Self-prescription of a gluten-free diet (GFD) without medical supervision is common in NCGS subjects, resulting in dietary restrictions that can cause macro- and micronutrient deficiencies. The primary aim was to describe dietary intake, including FODMAP, in subjects with self-reported gluten sensitivity on GFD in whom coeliac disease (CD) and wheat allergy were excluded. Secondary, clinical symptoms and health-related quality of life (HR-QoL) were examined. METHODS Baseline characteristics were obtained from 65 adults with self-reported NCGS on GFD recruited to a randomised placebo-controlled challenge trial at Oslo University Hospital. Dietary intake was obtained by a seven-day food record and symptoms recorded by questionnaires. RESULTS Mean proportions of energy were 43 E% from fat, 40 E% from carbohydrate and 17 E% from protein. Intakes of vitamin D, folic acid, calcium, iodine and iron were lower than recommended, mean (SD) 7.3 (5.8) μg, 235 (105) μg, 695 (309) mg, 81 (52) μg and 9.6 (7.5) mg, respectively. Mean (SD) intake of FODMAP was 11.6 g (8.7). Gastrointestinal symptoms as scored by 100 mm visual analogue scale (VAS) were all below 15 mm of which wind and bloating were the most expressed. Tiredness, concentration difficulties, fatigue and muscle/joint pain were scored highest among extra-intestinal symptoms. Gastrointestinal symptoms as scored by gastrointestinal symptom rating scale - irritable bowel syndrome version (GSRS-IBS) were correlated with mild depression (r = 0.43) and inversely correlated with five sub-domains of HR-QoL (-0.29 < r < -0.26). CONCLUSION Subjects with self-reported NCGS on GFD had high proportion of energy from fat and sub-optimal intakes of vitamin D, folic acid, calcium, iodine and iron. Despite GFD and moderate intake of FODMAP, the subjects reported various gastro- and extra-intestinal symptoms and reduced HR-QoL. The findings highlight the importance of dietary education and nutritional follow-up of subjects on GFD.
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A Durum Wheat Variety-Based Product Is Effective in Reducing Symptoms in Patients with Non-Celiac Gluten Sensitivity: A Double-Blind Randomized Cross-Over Trial.
Ianiro, G, Rizzatti, G, Napoli, M, Matteo, MV, Rinninella, E, Mora, V, Fanali, C, Leonetti, A, Benedettelli, S, Mele, MC, et al
Nutrients. 2019;(4)
Abstract
Patients with non-celiac gluten sensitivity (NCGS) do not have celiac disease, but their symptoms improve after a gluten-free diet (GFD). However, to date, it is uncertain if gluten or other components of wheat are responsible for these symptoms. The aim of this study was to compare the effects of an organic durum wheat variety with those of standard commercial wheat in patients with known NCGS. We performed a double-blind randomized cross-over trial of 42 patients (mean age 45 years, 8 men) with NCGS diagnosed according to the Salerno criteria and adherence to GFD for at least 12 weeks from screening. Enrolled subjects were randomly assigned to one the following groups of treatment: (A) a two-week diet with Senatore Cappelli wheat variety pasta; (B) a two-week diet with standard commercial pasta. Then, after a two-week washout period on gluten-free diet, each patient crossed over to the other treatment group. Symptoms were assessed through a modified version of the Gastrointestinal Symptom Rating Scale (GSRS), tailored on NCGS. Between April 2018 and July 2018, 42 patients with NCGS were enrolled in the study (70.6% females), and 34 patients completed the study. Patients reported lower overall symptoms scores after eating Senatore Cappelli pasta than standard pasta (p = 0.03) and also significantly lower scores in several specific gastrointestinal and extra-intestinal symptoms after eating Senatore Cappelli pasta than standard pasta, specifically, bloating (p = 0.04), abdominal distention (p = 0.004), eructation (p = 0.01), flatus (p = 0.02), feeling of incomplete evacuation (p = 0.001), dermatitis (p = 0.01), and limb numbness (p = 0.03). In our study, patients with NCGS experienced lower gastrointestinal and extra-intestinal symptom scores after eating the Senatore Cappelli wheat variety than a standard commercial wheat. Should our preliminary results be confirmed by further studies, new dietary alternatives may be available to patients with NCGS, with consequent health, economic, and social benefits.
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Clinical and Microbiological Effect of a Multispecies Probiotic Supplementation in Celiac Patients With Persistent IBS-type Symptoms: A Randomized, Double-Blind, Placebo-controlled, Multicenter Trial.
Francavilla, R, Piccolo, M, Francavilla, A, Polimeno, L, Semeraro, F, Cristofori, F, Castellaneta, S, Barone, M, Indrio, F, Gobbetti, M, et al
Journal of clinical gastroenterology. 2019;(3):e117-e125
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Abstract
GOALS The goals of this study were to evaluate the efficacy and safety of a probiotic mixture in patients with celiac disease (CD) with irritable bowel syndrome (IBS)-type symptoms despite a strict gluten-free diet (GFD). BACKGROUND About 30% of patients with CD adherent to a GFD suffer from IBS-type symptoms; a possible cause resides in the imbalances of the intestinal microbiota in CD. Probiotics may represent a potential treatment. STUDY CD patients with IBS-type symptoms entered a prospective, double-blind, randomized placebo-controlled study. A 6-week treatment period was preceded by a 2-week run-in and followed by a 6-week follow-up phase. Clinical data were monitored throughout the study by validated questionnaires: IBS Severity Scoring System (IBS-SSS); Gastrointestinal Symptom Rating Scale (GSRS); Bristol Stool Form Scale (BSFS); and IBS Quality of Life Questionnaire (IBS-QOL). The fecal microbiota were assayed using plate counts and 16S rRNA gene-based analysis. RESULTS In total, 109 patients were randomized to probiotics (n=54) or placebo (n=55). IBS-SSS and GSRS decreased significantly in probiotics, as compared with placebo [(-15.9%±14.8% vs. 8.2%±25.9%; P<0.001) and (-19.8%±16.6% vs. 12.9%±31.6%; P<0.001)], respectively. Treatment success was significantly higher in patients receiving probiotics, as compared with placebo (15.3% vs. 3.8%; P<0.04). Presumptive lactic acid bacteria, Staphylococcus and Bifidobacterium, increased in patients receiving probiotic treatment. No adverse events were reported. CONCLUSIONS A 6-week probiotic treatment is effective in improving the severity of IBS-type symptoms, in CD patients on strict GFD, and is associated with a modification of gut microbiota, characterized by an increase of bifidobacteria.
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Impact of FODMAP Content Restrictions on the Quality of Diet for Patients with Celiac Disease on a Gluten-Free Diet.
Bascuñán, KA, Elli, L, Pellegrini, N, Scricciolo, A, Lombardo, V, Doneda, L, Vecchi, M, Scarpa, C, Araya, M, Roncoroni, L
Nutrients. 2019;(9)
Abstract
Restrictive diets as gluten-free (GFD) or reduced in Fermentable, Oligosaccharides, Disaccharides, Monosaccharides, and Polyols (FODMAP) are used to improve gastrointestinal (GI) symptoms in sensitive individuals. Aiming at comparing the nutritional quality and effects of a regular GFD regimen (R-GFD) and a low-FODMAP GFD (LF-GFD), in 46 celiac patients with persistent GI symptoms we conducted a randomized, double-blind intervention-controlled study. Patients received a personalized diet, either a strict GFD (n = 21) or a LF-GFD (n = 25) for 21 days. A validated food-frequency questionnaire before intervention and a 7-day weighed-food record after the intervention assessed the diets. Patients were 41.1 ± 10.1 years (mean ± SD), 94% women, with mean BMI 21.8 ± 2.9 kg/m2. On day 21, patients on R-GFD still showed poor nutritional adequacy compared to dietary recommendations, with decreased energy intake, even though an improvement in carbohydrates and folates was observed (all p < 0.025). In both groups, intake of iron, calcium, vitamin D, sodium and folates did not meet daily recommendations. As expected, consumption of legumes and grains was lower and that of fruits was higher in the LF-GFD group than in the R-GFD one (all p < 0.05). The nutritional quality of both diets was not different. When restrictive diets are useful to improve the persistent GI symptoms, careful nutritional surveillance and counseling is mandatory.
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Text Message Intervention (TEACH) Improves Quality of Life and Patient Activation in Celiac Disease: A Randomized Clinical Trial.
Haas, K, Martin, A, Park, KT
The Journal of pediatrics. 2017;:62-67.e2
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Abstract
OBJECTIVE To determine the impact of the Text Message Educational Automated Compliance Help (TEACH) text message intervention as a pragmatic approach for patient engagement among adolescents with celiac disease (CD) as measured by gluten-free diet (GFD) adherence, patient activation, and quality of life (QOL). STUDY DESIGN Randomized controlled trial with patient recruitment at a pediatric, university-based hospital and through social media; 61 participants ages 12-24 years with CD diagnosed at least 1 year were enrolled. The TEACH intervention cohort received 45 unique text messages over a 3-month study period while the control group received standard of care treatment. Primary outcome measures included objective markers of GFD adherence included serum tissue transglutaminase IgA and deamidated gliadin peptide IgA levels. Secondary patient-reported outcomes collected via online survey included the Celiac Dietary Adherence Test, National Institutes of Health (NIH) Patient-Reported Outcomes Measurement Information System (PROMIS) Global Short Form measure of QOL, Celiac Symptom Index, and Patient Activation Measure. All measures were assessed at enrollment and after the 3-month study period. Statistical analysis performed using the 2-tailed paired Student t test. RESULTS Among the TEACH intervention group, there was significant improvement comparing enrollment scores with 3-month follow-up scores in patient activation (Patient Activation Measure score 63.1 vs 72.5, P?=?.01) and QOL (NIH PROMIS Global Mental Health 50.8 vs 53.3, P?=?.01 and NIH PROMIS Global Physical Health 50.8 vs 57.7, P?=?.03). There was no statistically significant difference in patient-reported or objectively measured GFD adherence. CONCLUSIONS TEACH is an effective intervention among patients with CD to improve patient activation and QOL, even among a cohort with GFD adherence at baseline. TRIAL REGISTRATION ClinicalTrials.gov: NCT02458898.
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Double-Blind Randomized Clinical Trial: Gluten versus Placebo Rechallenge in Patients with Lymphocytic Enteritis and Suspected Celiac Disease.
Rosinach, M, Fernández-Bañares, F, Carrasco, A, Ibarra, M, Temiño, R, Salas, A, Esteve, M
PloS one. 2016;(7):e0157879
Abstract
BACKGROUND The role of gluten as a trigger of symptoms in non-coeliac gluten sensitivity has been questioned. AIM: To demonstrate that gluten is the trigger of symptoms in a subgroup of patients fulfilling the diagnostic criteria for non-coeliac gluten sensitivity (NCGS), which presented with lymphocytic enteritis, positive celiac genetics and negative celiac serology. METHODS Double-blind randomized clinical trial of gluten vs placebo rechallenge. INCLUSION CRITERIA >18 years of age, HLA-DQ2/8+, negative coeliac serology and gluten-dependent lymphocytic enteritis, and GI symptoms, with clinical and histological remission at inclusion. Eighteen patients were randomised: 11 gluten (20 g/day) and 7 placebo. Clinical symptoms, quality of life (GIQLI), and presence of gamma/delta+ cells and transglutaminase deposits were evaluated. RESULTS 91% of patients had clinical relapse during gluten challenge versus 28.5% after placebo (p = 0.01). Clinical scores and GIQLI worsened after gluten but not after placebo (p<0.01). The presence of coeliac tissue markers at baseline biopsy on a gluten-free diet allowed classifying 9 out of the 18 (50%) patients as having probable 'coeliac lite' disease. CONCLUSION This proof-of-concept study indicates that gluten is the trigger of symptoms in a subgroup of patients fulfilling the diagnostic criteria for NCGS. They were characterized by positive celiac genetics, lymphocytic enteritis, and clinical and histological remission after a gluten-free diet. TRIAL REGISTRATION ClinicalTrials.gov NCT02472704.
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Dissemination of an online theory-based intervention to improve gluten-free diet adherence in coeliac disease: the relationship between acceptability, effectiveness, and attrition.
Sainsbury, K, Mullan, B, Sharpe, L
International journal of behavioral medicine. 2015;(3):356-64
Abstract
BACKGROUND Both acceptability and behaviour change data provide important information about the likelihood of success of an intervention when disseminated outside the research context. Despite this, few studies have combined such data for use in ongoing intervention development. PURPOSE To assess the acceptability and feasibility of an online intervention to improve gluten-free diet (GFD) adherence in coeliac disease, and to examine the relationships with participant characteristics, attrition, and effectiveness to inform ongoing intervention developments to ultimately reduce attrition and improve the reach and effectiveness of the programme. METHODS All participants completed measures of GFD adherence, theory of planned behaviour variables, psychological symptoms, and demographic and disease characteristics. Acceptability and feasibility ratings were obtained at the conclusion of each of the six intervention modules. Chi-square analyses were used to examine differences between completers and non-completers, and Spearman's correlations were used to determine the relationships between participant characteristics, effectiveness, and acceptability and feasibility. RESULTS Participants who rated the early modules less favourably were more likely to drop-out of the intervention. Acceptability and feasibility ratings were also associated with the presence of psychological symptoms, use of adaptive coping strategies, GFD duration, and attitude change. CONCLUSIONS The findings suggest that changes to the structure and implementation of the intervention may be useful in minimising attrition and maximising effectiveness for future dissemination in a wider coeliac disease population.
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A randomized, double-blind study of larazotide acetate to prevent the activation of celiac disease during gluten challenge.
Leffler, DA, Kelly, CP, Abdallah, HZ, Colatrella, AM, Harris, LA, Leon, F, Arterburn, LA, Paterson, BM, Lan, ZH, Murray, JA
The American journal of gastroenterology. 2012;(10):1554-62
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Abstract
OBJECTIVES In patients with celiac disease, enteropathy is caused by the entry of gluten peptides into the lamina propria of the intestine, in which their immunogenicity is potentiated by tissue transglutaminase (tTG) and T-helper type 1-mediated immune responses are triggered. Tight junction disassembly and paracellular permeability are believed to have an important role in the transport of gluten peptides to the lamina propria. Larazotide acetate is a tight-junction regulator peptide that, in vitro, prevents the opening of intestinal epithelial tight junctions. The aim of this study was to evaluate the efficacy and tolerability of larazotide acetate in protecting against gluten-induced intestinal permeability and gastrointestinal symptom severity in patients with celiac disease. METHODS In this dose-ranging, placebo-controlled study, 86 patients with celiac disease controlled through diet were randomly assigned to larazotide acetate (0.25, 1, 4, or 8 mg) or placebo three times per day with or without gluten challenge (2.4 g/day) for 14 days. The primary efficacy outcome was the urinary lactulose/mannitol (LAMA) fractional excretion ratio. Secondary endpoints included gastrointestinal symptom severity, quality-of-life measures, and antibodies to tTG. RESULTS LAMA measurements were highly variable in the outpatient setting. The increase in LAMA ratio associated with the gluten challenge was not statistically significantly greater than the increase in the gluten-free control. Among patients receiving the gluten challenge, the difference in the LAMA ratios for the larazotide acetate and placebo groups was not statistically significant. However, larazotide acetate appeared to limit gluten-induced worsening of gastrointestinal symptom severity as measured by the Gastrointestinal Symptom Rating Scale at some lower doses but not at the higher dose. Symptoms worsened significantly in the gluten challenge-placebo arm compared with the placebo-placebo arm, suggesting that 2.4 g of gluten per day is sufficient to induce reproducible gluten toxicity. Larazotide acetate was generally well tolerated. No serious adverse events were observed. The most common adverse events were headache and urinary tract infection. CONCLUSIONS LAMA variability in the outpatient setting precluded accurate assessment of the effect of larazotide acetate on intestinal permeability. However, some lower doses of larazotide acetate appeared to prevent the increase in gastrointestinal symptom severity induced by gluten challenge.