Effect of Gluten-Free Diet on Gut Microbiota Composition in Patients with Celiac Disease and Non-Celiac Gluten/Wheat Sensitivity

Celiac disease (CD) and non-celiac gluten/wheat sensitivity (NCG/WS) are the two most frequent conditions belonging to gluten-related disorders (GRDs). Both these diseases are triggered and worsened by gluten proteins ingestion, although other components, such as amylase/trypsin inhibitors (ATI) and fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs), seem to be involved in the NCG/WS onset. Therefore, the only effective treatment to date is the long-life adherence to a strictly gluten-free diet. Recently, increasing attention has been paid to the intestinal barrier, a dynamic system comprising various components, which regulate the delicate crosstalk between metabolic, motor, neuroendocrine and immunological functions. Among the elements characterizing the intestinal barrier, the microbiota plays a key role, modulating the gut integrity maintenance, the immune response and the inflammation process, linked to the CD and NCG/WS outbreak. This narrative review addresses the most recent findings on the gut microbiota modulation induced by the gluten-free diet (GFD) in healthy, CD and NCG/WS patients.

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Effects of Dietary Fibres on Acute Indomethacin-Induced Intestinal Hyperpermeability in the Elderly: A Randomised Placebo Controlled Parallel Clinical Trial

Nutrients ◽

10.3390/nu12071954 ◽

2020 ◽

Vol 12 (7) ◽

pp. 1954

Author(s):

John-Peter Ganda Mall ◽

Frida Fart ◽

Julia A. Sabet ◽

Carl Mårten Lindqvist ◽

Ragnhild Nestestog ◽

...

Keyword(s):

Gut Microbiota ◽

Barrier Function ◽

Intestinal Barrier ◽

The Elderly ◽

Intestinal Barrier Function ◽

Elderly Subjects ◽

Microbiota Composition ◽

Dietary Fibres ◽

Gut Microbiota Composition

The effect of dietary fibres on intestinal barrier function has not been well studied, especially in the elderly. We aimed to investigate the potential of the dietary fibres oat β-glucan and wheat arabinoxylan to strengthen the intestinal barrier function and counteract acute non-steroid anti-inflammatory drug (indomethacin)-induced hyperpermeability in the elderly. A general population of elderly subjects (≥65 years, n = 49) was randomised to a daily supplementation (12g/day) of oat β-glucan, arabinoxylan or placebo (maltodextrin) for six weeks. The primary outcome was change in acute indomethacin-induced intestinal permeability from baseline, assessed by an in vivo multi-sugar permeability test. Secondary outcomes were changes from baseline in: gut microbiota composition, systemic inflammatory status and self-reported health. Despite a majority of the study population (85%) showing a habitual fibre intake below the recommendation, no significant effects on acute indomethacin-induced intestinal hyperpermeability in vivo or gut microbiota composition were observed after six weeks intervention with either dietary fibre, compared to placebo.

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Irritable Bowel Syndrome and Gluten-Related Disorders

Nutrients ◽

10.3390/nu12041117 ◽

2020 ◽

Vol 12 (4) ◽

pp. 1117 ◽

Cited By ~ 3

Author(s):

Paolo Usai-Satta ◽

Gabrio Bassotti ◽

Massimo Bellini ◽

Francesco Oppia ◽

Mariantonia Lai ◽

...

Keyword(s):

Irritable Bowel Syndrome ◽

Celiac Disease ◽

The Other ◽

Gluten Free Diet ◽

Gluten Free ◽

Gut Permeability ◽

Online Search ◽

Systematic Screening ◽

Wheat Sensitivity ◽

Irritable Bowel

Background: Irritable bowel syndrome (IBS) is frequently associated with celiac disease (CD) and nonceliac gluten/wheat sensitivity (NCGS/NCWS), but epidemiological and pathophysiological aspects are still unclear. Furthermore, a gluten-free diet (GFD) can positively influence IBS symptoms. Methods: A comprehensive online search for IBS related to CD, NCGS and GFD was made using the Pubmed, Medline and Cochrane databases. Results: Although a systematic screening for CD in IBS is not recommended, CD prevalence can be increased in diarrhea-predominant IBS patients. On the other hand, IBS symptoms can be persistent in treated CD patients, and their prevalence tends to decrease on a GFD. IBS symptoms may overlap and be similar to those associated to nonceliac gluten and/or wheat sensitivity. Increased gut permeability could explain the gluten/wheat effects in IBS patients. Finally, a GFD could improve symptoms in a subgroup of IBS patients. Conclusions: The possible interplay between IBS and gluten-related disorders represents a scientifically and clinically challenging issue. Further studies are needed to confirm these data and better clarify the involved pathophysiological mechanisms.

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Probiotics in Celiac Disease

Nutrients ◽

10.3390/nu10121824 ◽

2018 ◽

Vol 10 (12) ◽

pp. 1824 ◽

Cited By ~ 13

Author(s):

Fernanda Cristofori ◽

Flavia Indrio ◽

Vito Miniello ◽

Maria De Angelis ◽

Ruggiero Francavilla

Keyword(s):

Celiac Disease ◽

Gut Microbiota ◽

Intestinal Microbiota ◽

Gastrointestinal Symptoms ◽

Human Microbiome ◽

Gluten Free Diet ◽

Gluten Free ◽

Microbial Composition ◽

Close Link ◽

Host Protection

Recently, the interest in the human microbiome and its interplay with the host has exploded and provided new insights on its role in conferring host protection and regulating host physiology, including the correct development of immunity. However, in the presence of microbial imbalance and particular genetic settings, the microbiome may contribute to the dysfunction of host metabolism and physiology, leading to pathogenesis and/or the progression of several diseases. Celiac disease (CD) is a chronic autoimmune enteropathy triggered by dietary gluten exposure in genetically predisposed individuals. Despite ascertaining that gluten is the trigger in CD, evidence has indicated that intestinal microbiota is somehow involved in the pathogenesis, progression, and clinical presentation of CD. Indeed, several studies have reported imbalances in the intestinal microbiota of patients with CD that are mainly characterized by an increased abundance of Bacteroides spp. and a decrease in Bifidobacterium spp. The evidence that some of these microbial imbalances still persist in spite of a strict gluten-free diet and that celiac patients suffering from persistent gastrointestinal symptoms have a desert gut microbiota composition further support its close link with CD. All of this evidence gives rise to the hypothesis that probiotics might play a role in this condition. In this review, we describe the recent scientific evidences linking the gut microbiota in CD, starting from the possible role of microbes in CD pathogenesis, the attempt to define a microbial signature of disease, the effect of a gluten-free diet and host genetic assets regarding microbial composition to end in the exploration of the proof of concept of probiotic use in animal models to the most recent clinical application of selected probiotic strains.

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Intestinal Permeability in Children with Celiac Disease after the Administration of Oligofructose-Enriched Inulin into a Gluten-Free Diet—Results of a Randomized, Placebo-Controlled, Pilot Trial

Nutrients ◽

10.3390/nu12061736 ◽

2020 ◽

Vol 12 (6) ◽

pp. 1736 ◽

Cited By ~ 1

Author(s):

Natalia Drabińska ◽

Urszula Krupa-Kozak ◽

Elżbieta Jarocka-Cyrta

Keyword(s):

Celiac Disease ◽

Intestinal Permeability ◽

Pilot Trial ◽

Intestinal Barrier ◽

Substantial Effect ◽

Gluten Free Diet ◽

Gluten Free ◽

Epithelial Surface ◽

Fatty Acid Binding ◽

Sugar Absorption

Abnormalities in the intestinal barrier are a possible cause of celiac disease (CD) development. In animal studies, the positive effect of prebiotics on the improvement of gut barrier parameters has been observed, but the results of human studies to date remain inconsistent. Therefore, this study aimed to evaluate the effect of twelve-week supplementation of a gluten-free diet (GFD) with prebiotic oligofructose-enriched inulin (10 g per day) on the intestinal permeability in children with CD treated with a GFD. A pilot, randomized, placebo-controlled nutritional intervention was conducted in 34 children with CD, being on a strict GFD. Sugar absorption test (SAT) and the concentrations of intestinal permeability markers, such as zonulin, intestinal fatty acid-binding protein, claudin-3, calprotectin, and glucagon-like peptide-2, were measured. We found that the supplementation with prebiotic did not have a substantial effect on barrier integrity. Prebiotic intake increased excretion of mannitol, which may suggest an increase in the epithelial surface. Most children in our study seem to have normal values for intestinal permeability tests before the intervention. For individuals with elevated values, improvement in calprotectin and SAT was observed after the prebiotic intake. This preliminary study suggests that prebiotics may have an impact on the intestinal barrier, but it requires confirmation in studies with more subjects with ongoing leaky gut.

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Aryl hydrocarbon receptor ligand production by the gut microbiota is decreased in celiac disease leading to intestinal inflammation

Science Translational Medicine ◽

10.1126/scitranslmed.aba0624 ◽

2020 ◽

Vol 12 (566) ◽

pp. eaba0624 ◽

Cited By ~ 3

Author(s):

Bruno Lamas ◽

Leticia Hernandez-Galan ◽

Heather J. Galipeau ◽

Marco Constante ◽

Alexandra Clarizio ◽

...

Keyword(s):

Celiac Disease ◽

Gut Microbiota ◽

Aryl Hydrocarbon Receptor ◽

Intestinal Inflammation ◽

Susceptibility Gene ◽

Rrna Gene ◽

Microbiota Composition ◽

Aryl Hydrocarbon ◽

Pathway Activation ◽

Gut Microbiota Composition

Metabolism of tryptophan by the gut microbiota into derivatives that activate the aryl hydrocarbon receptor (AhR) contributes to intestinal homeostasis. Many chronic inflammatory conditions, including celiac disease involving a loss of tolerance to dietary gluten, are influenced by cues from the gut microbiota. We investigated whether AhR ligand production by the gut microbiota could influence gluten immunopathology in nonobese diabetic (NOD) mice expressing DQ8, a celiac disease susceptibility gene. NOD/DQ8 mice, exposed or not exposed to gluten, were subjected to three interventions directed at enhancing AhR pathway activation. These included a high-tryptophan diet, gavage with Lactobacillus reuteri that produces AhR ligands or treatment with an AhR agonist. We investigated intestinal permeability, gut microbiota composition determined by 16S rRNA gene sequencing, AhR pathway activation in intestinal contents, and small intestinal pathology and inflammatory markers. In NOD/DQ8 mice, a high-tryptophan diet modulated gut microbiota composition and enhanced AhR ligand production. AhR pathway activation by an enriched tryptophan diet, treatment with the AhR ligand producer L. reuteri, or pharmacological stimulation using 6-formylindolo (3,2-b) carbazole (Ficz) decreased immunopathology in NOD/DQ8 mice exposed to gluten. We then determined AhR ligand production by the fecal microbiota and AhR activation in patients with active celiac disease compared to nonceliac control individuals. Patients with active celiac disease demonstrated reduced AhR ligand production and lower intestinal AhR pathway activation. These results highlight gut microbiota-dependent modulation of the AhR pathway in celiac disease and suggest a new therapeutic strategy for treating this disorder.

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The Dietary Intervention of Transgenic Low-Gliadin Wheat Bread in Patients with Non-Celiac Gluten Sensitivity (NCGS) Showed No Differences with Gluten Free Diet (GFD) but Provides Better Gut Microbiota Profile

Nutrients ◽

10.3390/nu10121964 ◽

2018 ◽

Vol 10 (12) ◽

pp. 1964 ◽

Cited By ~ 8

Author(s):

Carmen Haro ◽

Myriam Villatoro ◽

Luis Vaquero ◽

Jorge Pastor ◽

María Giménez ◽

...

Keyword(s):

Gut Microbiota ◽

Rating Scale ◽

Wheat Bread ◽

Rrna Gene ◽

Gluten Sensitivity ◽

Microbiota Composition ◽

Gluten Free ◽

Two Phases ◽

Basal Phase ◽

Gut Microbiota Composition

The study evaluated the symptoms, acceptance, and digestibility of bread made from transgenic low-gliadin wheat, in comparison with gluten free bread, in Non-coeliac gluten sensitivity (NCGS) patients, considering clinical/sensory parameters and gut microbiota composition. This study was performed in two phases of seven days each, comprising a basal phase with gluten free bread and an E82 phase with low-gliadin bread. Gastrointestinal clinical symptoms were evaluated using the Gastrointestinal Symptom Rating Scale (GSRS) questionnaire, and stool samples were collected for gluten immunogenic peptides (GIP) determination and the extraction of gut microbial DNA. For the basal and E82 phases, seven and five patients, respectively, showed undetectable GIPs content. The bacterial 16S rRNA gene V1-V2 hypervariable regions were sequenced using the Illumina MiSeq platform and downstream analysis was done using a Quantitative Insights into Microbial Ecology (QIIME) pipeline. No significant differences in the GSRS questionnaires were observed between the two phases. However, we observed a significantly lower abundance of some gut genera Oscillospira, Dorea, Blautia, Bacteroides, Coprococcus, and Collinsella, and a significantly higher abundance of Roseburia and Faecalibacterium genera during the E82 phase compared with the basal phase. The consumption of low-gliadin bread E82 by NCGS subjects induced potentially positive changes in the gut microbiota composition, increasing the butyrate-producing bacteria and favoring a microbial profile that is suggested to have a key role in the maintenance or improvement of gut permeability.

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Nostoc sphaeroids Kütz ameliorates hyperlipidemia and maintains the intestinal barrier and gut microbiota composition of high‐fat diet mice

Food Science & Nutrition ◽

10.1002/fsn3.1521 ◽

2020 ◽

Vol 8 (5) ◽

pp. 2348-2359 ◽

Cited By ~ 1

Author(s):

Fenfen Wei ◽

Yinlu Liu ◽

Cuicui Bi ◽

Sheng Chen ◽

Yulan Wang ◽

...

Keyword(s):

Gut Microbiota ◽

High Fat Diet ◽

Intestinal Barrier ◽

Microbiota Composition ◽

High Fat ◽

Gut Microbiota Composition

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Altered Duodenal Microbiota Composition in Celiac Disease Patients Suffering From Persistent Symptoms on a Long-Term Gluten-Free Diet

The American Journal of Gastroenterology ◽

10.1038/ajg.2014.355 ◽

2014 ◽

Vol 109 (12) ◽

pp. 1933-1941 ◽

Cited By ~ 105

Author(s):

Pirjo Wacklin ◽

Pilvi Laurikka ◽

Katri Lindfors ◽

Pekka Collin ◽

Teea Salmi ◽

...

Keyword(s):

Celiac Disease ◽

Gluten Free Diet ◽

Microbiota Composition ◽

Gluten Free ◽

Persistent Symptoms

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Non-celiac wheat sensitivity: rationality and irrationality of a gluten-free diet in individuals affected with non-celiac disease: a review

BMC Gastroenterology ◽

10.1186/s12876-020-01568-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Consolato Sergi ◽

Vincenzo Villanacci ◽

Antonio Carroccio

Keyword(s):

Celiac Disease ◽

Duodenal Mucosa ◽

Gluten Free Diet ◽

Diagnostic Process ◽

Gluten Free ◽

Accurate Analysis ◽

Superficial Epithelium ◽

Wheat Sensitivity ◽

Irritable Bowel ◽

The Relationship

AbstractNon-celiac gluten or wheat sensitivity (NCWS) is a “clinical entity induced by the ingestion of wheat leading to intestinal and/or extraintestinal symptoms that improve once the wheat-containing foodstuff is removed from the diet, and celiac disease and wheat allergy have been excluded”. This mostly accepted definition raises several points that remain controversial on this condition. In the present review, the authors summarize the most recent advances in the clinic and research on NCWS through an accurate analysis of different studies. We screened PubMed, Medline, Embase, and Scopus using the keywords “non-celiac gluten sensitivity”, “non-celiac wheat sensitivity”, and “diagnosis”. We would like to emphasize two main points, including (A) the controversial clinical and etiological aspects in different trials and experiences with particular attention to the Salerno criteria for the diagnosis of NCWS and (B) the histological aspects. The etiology of NCWS remains controversial, and the relationship with irritable bowel syndrome is obscure. Histologically, the duodenal mucosa may show a variable pattern from unremarkable to a slight increase in the number of T lymphocytes in the superficial epithelium of villi. The endorsement of this disease is based on a positive response to a gluten-free diet for a limited period, followed by the reappearance of symptoms after gluten challenge. The Salerno expert criteria may help to diagnose NCWS accurately. Social media and inaccurate interpretation of websites may jeopardize the diagnostic process if individuals self-label as gluten intolerant.

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