Pathogenesis Of Celiac Disease Research Articles

Alterations in Intestinal Microbiota of Children With Celiac Disease at the Time of Diagnosis and on a Gluten-free Diet

Background And AimsIt is not clear whether alterations in the intestinal microbiota of children with celiac disease (CD) cause the disease or are a result of disease and/or its treatment with a gluten-free diet (GFD).MethodsWe obtained 167 fecal samples from 141 children (20 with new-onset CD, 45 treated with a GFD, 57 healthy children, and 19 unaffected siblings of children with CD) in Glasgow, Scotland. Samples were analyzed by 16S ribosomal RNA sequencing, and diet-related metabolites were measured by gas chromatography. We obtained fecal samples from 13 children with new-onset CD after 6 and 12 months on a GFD. Relationships between microbiota with diet composition, gastrointestinal function, and biomarkers of GFD compliance were explored.ResultsMicrobiota α diversity did not differ among groups. Microbial dysbiosis was not observed in children with new-onset CD. In contrast, 2.8% (Bray-Curtis dissimilarity index, P = .025) and 2.5% (UniFrac distances, P = .027) of the variation in microbiota composition could be explained by the GFD. Between 3% and 5% of all taxa differed among all group comparisons. Eleven distinctive operational taxonomic units composed a microbe signature specific to CD with high diagnostic probability. Most operational taxonomic units that differed between patients on a GFD with new-onset CD vs healthy children were associated with nutrient and food group intake (from 75% to 94%) and with biomarkers of gluten ingestion. Fecal levels of butyrate and ammonia decreased during the GFD.ConclusionsAlthough several alterations in the intestinal microbiota of children with established CD appear to be effects of a GFD, specific bacteria were found to be distinct biomarkers of CD. Studies are needed to determine whether these bacteria contribute to pathogenesis of CD.

Celiac Disease

Celiac disease is a multisystem autoimmune disorder, which is induced by dietary gluten exposure. This disease usually found in European population, but with the increase of Asian population tendency to eat western style, which contain gluten, celiac disease frequency is expected to increase in Asian population for the near future. The finding of diagnostic modalities which is highly sensitive and specific, starting with the antigliadin, and then the antiendomysium and anti-transglutaminase antibodies, has increased the awareness of clinicians and patients towards this condition. The understanding of definition, pathogenesis, diagnostic procedure, and current management of celiac disease is needed to avoid morbidity and mortality of this disease.

Serum Level and Gene Expression of Interleukin-15 Do Not Correlate with Villous Atrophy in Celiac Disease Patients.

Background and Aims: Interleukin-15 (IL-15) is a key player in the pathogenesis of celiac disease (CD). We investigated the functional role of IL-15 in the process of epithelial cell phenotypic modification at different stages of CD. Materials and Methods: In this study, we looked for correlations between the IL-15 mRNA levels in duodenal tissue and serum protein levels in a cohort of Iranian patients affected by CD based on the degree of histopathology. Ninety-five formalin-fixed, paraffin-embedded duodenal tissue specimens were collected: 23 with a Marsh I value; 30 with a Marsh II value; 32 with a Marsh III value; and 10 normal controls. The expression levels of the IL-15 gene in these biopsy specimens were determined by real-time quantitative polymerase chain reaction (qPCR), and IL-15 serum protein concentrations were determined by enzyme-linked immunosorbent assay and compared to tissue expression. Results: The IL-15 mRNA levels were higher in patients with Marsh II compared with the control group, and the Marsh I, and Marsh III groups. The differences between the Marsh II and Marsh I patients were statistically significant (p = 0.03). Similarly, the serum concentration of IL-15 was higher in Marsh II patients compared to those with Marsh I and Marsh III lesions, although the differences were not statistically significant (p = 0.221). Conclusions: Our results demonstrate that IL-15 gene expression might be elevated only in the early stages of CD onset (and histological damage) and that IL-15 serum levels do not significantly correlate with its tissue expression whatever the degree of histopathology.

Brain Opioid Activity and Oxidative Injury: Different Molecular Scenarios Connecting Celiac Disease and Autistic Spectrum Disorder.

Celiac Disease (CD) is an immune-mediated disease triggered by the ingestion of wheat gliadin and related prolamins from other cereals, such as barley and rye. Immunity against these cereal-derived proteins is mediated by pro-inflammatory cytokines produced by both innate and adaptive system response in individuals unable to adequately digest them. Peptides generated in this condition are absorbed across the gut barrier, which in these patients is characterized by the deregulation of its permeability. Here, we discuss a possible correlation between CD and Autistic Spectrum Disorder (ASD) pathogenesis. ASD can be induced by an excessive and inappropriate brain opioid activity during the neonatal period. Cereal-derived peptides produced in celiac patients cross the blood–brain barrier and bind to endogenous opioid receptors interfering with neurotransmission and generating deleterious effects on brain maturation, learning and social relations. Moreover, an increase in oxidative stress and a decrease in the antioxidant capacity, as well as an extended mitochondrial impairment in the brain, could represent a possible connection between ASD and CD. Therefore, we critically discuss the proposed relationship between ASD and CD and the possible usefulness of a gluten-free diet in ASD patients.

Intestinal Anti-tissue Transglutaminase2 Autoantibodies: Pathogenic and Clinical Implications for Celiac Disease.

Celiac disease (CD) is a systemic disease that primarily affects the small intestine. The presence of anti-tissue transglutaminase 2 (anti-TG2) antibodies in the serum, as well as the presence of autoimmune phenomena, account for the inclusion of CD among autoimmune diseases. Anti-TG2 autoantibodies are produced at intestinal level, where they are deposited even before they appear in circulation. The pathogenic events that lead to their production are still not completely defined, but a central role seems to be played by gliadin-specific T cells. Interestingly, limited somatic mutations have been observed in VH and VL genes in TG2-specific plasma cells, another important aspect being the biased use of a heavy chain encoded by the VH5 gene. Conflicting data have been produced over the years on the effect of anti-TG2 antibodies on TG2 function. Although the presence of anti-TG2 antibodies in serum is considered a hallmark of CD and relevant from a clinical viewpoint, the role of these autoantibodies in the development of the celiac lesion remains to be defined. In the years, different technical approaches have been implemented to detect and measure intestinal CD-associated autoantibody production. Two aspects can make intestinal anti-TG2 antibodies relevant: from a clinical viewpoint: the first is their proposed ability in potential coeliac patients to predict the development of a full-blown enteropathy; the second is their possible role in revealing a condition of reactivity to gluten in patients with no circulating CD-associated autoantibodies. In fact, the detection of CD-specific autoantibodies production in the intestine, in the absence of serum positivity for the same antibodies, could be suggestive of a very early condition of gluten reactivity; alternatively, it could be not specific for CD and merely attributable to intestinal inflammation. In conclusion, the role of mucosal anti-TG2 antibodies in pathogenesis of CD is unknown. Their presence, the modalities of their production, their gluten dependence render them a unique model to study autoimmunity.

Identification of Isopeptides Between Human Tissue Transglutaminase and Wheat, Rye, and Barley Gluten Peptides

Celiac disease (CD) is a chronic immune-mediated enteropathy of the small intestine, which is triggered by the ingestion of storage proteins (gluten) from wheat, rye, and barley in genetically predisposed individuals. Human tissue transglutaminase (TG2) plays a central role in the pathogenesis of CD, because it is responsible for specific gluten peptide deamidation and covalent crosslinking, resulting in the formation of Nε-(γ-glutamyl)-lysine isopeptide bonds. The resulting TG2-gluten peptide complexes are assumed to cause the secretion of anti-TG2 autoantibodies, but the underlying mechanisms are only partly known. To gain more insight into the structures of these complexes, the aim of our study was to identify TG2-gluten isopeptides. With the use of discovery-driven as well as targeted nanoscale liquid chromatography tandem mass spectrometry, we detected 29 TG2-gluten isopeptides in total, involving seven selected TG2 lysine residues (K205, K265, K429, K468, K590, K600, K677). Several gluten peptides carried known B-cell epitopes and/or T-cell epitopes, either intact 9-mer core regions or partial sequences, as well as sequences bearing striking similarities to already known epitopes. These novel insights into the molecular structures of TG2-gluten peptide complexes may help clarify their physiological relevance in the initiation of CD autoimmunity and the role of anti-TG2 autoantibodies.

Celiac disease: a multi-faceted medical condition.

Celiac disease (CD) is a systemic condition of autoimmune origin, affecting genetically predisposed individuals who at some point lose tolerance towards dietary gluten. Prevalence in the general population is 0.5 - 1%, with a higher frequency in women. The most important environmental factor for CD is ingestion of specific gluten peptides. It triggers a sequence of molecular events, involving the intestinal permeability and the immune system, which ends in damage of the intestinal mucosa. A number of studies have demonstrated the correlation between the intestinal microbiota and celiac disease. MicroRNAs through their regulatory role on gene expression have been implicated in the pathogenesis of CD and suggested as potential biomarkers. In the pediatric and adult population, CD displays different clusters of clinical symptoms. Persistent diarrhea, abdominal pain and involuntary weight loss are the classic symptoms of CD. In the majority of cases diagnosis relies on the combination of serum autoantibodies (anti-transglutaminase and anti-endomisium IgA) and duodenal biopsy showing villous atrophy, crypt hyperplasia and intraepithelial lymphocytes. Observance of a lifelong gluten-free diet, which interrupts the immune response to gluten peptides, is the only effective treatment of CD.

Intestinal ex vivo organoid culture reveals altered programmed crypt stem cells in patients with celiac disease

The ex vivo generation of gastrointestinal organoids from crypt stem cells opens up the possibility of new research approaches investigating gastrointestinal diseases. We used this technology to study differences between healthy controls and patients with celiac disease (CD). We noticed distinct dissimilarities in the phenotypes of organoids between our study groups and found considerable variations in their gene expression. Extracellular matrix genes involved in epithelial-mesenchymal transition are expressed most differently. In addition, we demonstrated epigenetic modifications that might be responsible for the different organoid gene expression thus accounting for a deranged crypt/villus axis development in CD. The organoids have proven valuable to demonstrate fundamental differences in duodenal derived organoids between healthy controls and patients with CD and thus are a suitable tool to gain new insights in pathogenesis of CD.

Transcriptional and Ultrastructural Analyses Suggest Novel Insights into Epithelial Barrier Impairment in Celiac Disease

Disruption of epithelial junctional complex (EJC), especially tight junctions (TJ), resulting in increased intestinal permeability, is supposed to activate the enhanced immune response to gluten and to induce the development of celiac disease (CD). This study is aimed to present the role of EJC in CD pathogenesis. To analyze differentially expressed genes the next-generation mRNA sequencing data from CD326+ epithelial cells isolated from non-celiac and celiac patients were involved. Ultrastructural studies with morphometry of EJC were done in potential CD, newly recognized active CD, and non-celiac controls. The transcriptional analysis suggested disturbances of epithelium and the most significant gene ontology enriched terms in epithelial cells from CD patients related to the plasma membrane, extracellular exome, extracellular region, and extracellular space. Ultrastructural analyses showed significantly tighter TJ, anomalies in desmosomes, dilatations of intercellular space, and shorter microvilli in potential and active CD compared to controls. Enterocytes of fetal-like type and significantly wider adherence junctions were observed only in active CD. In conclusion, the results do not support the hypothesis that an increased passage of gluten peptides by unsealing TJ precedes CD development. However, increased intestinal permeability due to abnormality of epithelium might play a role in CD onset.

IL-15, gluten and HLA-DQ8 drive tissue destruction in coeliac disease.

Coeliac disease (CeD) is a complex, polygenic inflammatory enteropathy caused by exposure to dietary gluten that selectively occurs in a subset of genetically susceptible HLA-DQ8 and HLA-DQ2 individuals1,2. The need to develop non-dietary treatments is now widely recognized3, but it is hampered by the lack of a pathophysiologically relevant gluten- and HLA-dependent preclinical model. Furthermore, while human studies have led to major advances in our understanding of CeD pathogenesis4, direct demonstration of the respective roles of disease-predisposing HLA molecules, and adaptive and innate immunity in the development of tissue damage is missing. To address these unmet needs, we engineered a mouse model that reproduces the dual overexpression of IL-15 in the gut epithelium and the lamina propria (LP) characteristic of active CeD, expresses the predisposing HLA-DQ8 molecule, and develops villous atrophy (VA) upon gluten ingestion. We show that overexpression of IL-15 in both the epithelium and LP is required for the development of VA, demonstrating the location-dependent central role of IL-15 in CeD pathogenesis. Furthermore, our study reveals that CD4+ T cells and HLA-DQ8 are required for VA development, because of their critical role in the licensing of cytotoxic T cells to mediate intestinal epithelial cell (IEC) lysis. Finally, it establishes that IFN-γ and transglutaminase 2 (TG2) are central for tissue destruction. This mouse model, by reflecting the complex interplay between gluten, genetics and the IL-15-driven tissue inflammation, represents a powerful preclinical model for the characterization of cellular circuits critically involved in intestinal tissue damage in CeD, and the identification and testing of new therapeutic strategies.

Constitutive Differential Features of Type 2 Transglutaminase in Cells Derived from Celiac Patients and from Healthy Subjects.

Type 2 transglutaminase (TG2) is a ubiquitous enzyme able to modify gliadin peptides introduced into the organism through the diet. By means of its catalytic activity, TG2 seems to have an important pathogenetic role in celiac disease (CD), an inflammatory intestinal disease caused by the ingestion of gluten-containing cereals. A strong autoimmune response to TG2 characterizes CD development. Anti-TG2 antibodies specifically derange the uptake of the α-gliadin peptide 31–43 by control, but not by celiac dermal fibroblasts, underlying some different constitutive features regarding TG2 in healthy and celiac subjects. Our aim was to investigate whether these differences depended on a different TG2 subcellular distribution and whether peptide 31–43 differentially regulated TG2 expression and activity in cells of the two groups of subjects. We found that TG2 was more abundantly associated with membranes of celiac fibroblasts than of control cells, in particular with the early endosomal and autophagic compartments. We also found that peptide 31–43 differentially affected TG2 expression and activity in the two groups of cells, activating TG2 more in control than in celiac cells and inducing TG2 expression in celiac cells, but not in control ones. The different TG2 subcellular localization and the different way the peptide 31–43 modulates TG2 activity and availability into control and CD cells suggested that TG2 is involved in the definition of a constitutive CD cellular phenotype, thus having an important and still undefined role in CD pathogenesis.

Pathogenesis of Celiac Disease and Other Gluten Related Disorders in Wheat and Strategies for Mitigating Them.

Wheat is a major cereal crop providing energy and nutrients to the billions of people around the world. Gluten is a structural protein in wheat, that is necessary for its dough making properties, but it is responsible for imparting certain intolerances among some individuals, which are part of this review. Most important among these intolerances is celiac disease, that is gluten triggered T-cell mediated autoimmune enteropathy and results in villous atrophy, inflammation and damage to intestinal lining in genetically liable individuals containing human leukocyte antigen DQ2/DQ8 molecules on antigen presenting cells. Celiac disease occurs due to presence of celiac disease eliciting epitopes in gluten, particularly highly immunogenic alpha-gliadins. Another gluten related disorder is non-celiac gluten-sensitivity in which innate immune-response occurs in patients along with gastrointestinal and non-gastrointestinal symptoms, that disappear upon removal of gluten from the diet. In wheat allergy, either IgE or non-IgE mediated immune response occurs in individuals after inhalation or ingestion of wheat. Following a life-long gluten-free diet by celiac disease and non-celiac gluten-sensitivity patients is very challenging as none of wheat cultivar or related species stands safe for consumption. Hence, different molecular biology, genetic engineering, breeding, microbial, enzymatic, and chemical strategies have been worked upon to reduce the celiac disease epitopes and the gluten content in wheat. Currently, only 8.4% of total population is affected by wheat-related issues, while rest of population remains safe and should not remove wheat from the diet, based on false media coverage.

Coeliac disease from pathogenesis to clinical practice: current concepts.

Coeliac disease is an autoimmune disease affecting the small intestine in genetically predisposed subjects following the ingestion of gluten. Many advances have been made towards understanding the pathogenic mechanisms that underlie the development of coeliac disease. The interaction between genetic, environmental and immunological factors is the main pathophysiological aspect, but over the last few years growing importance has been given to the role of the intestinal barrier and in particular to the alteration of intestinal microbiota. Clinical manifestations mainly include signs and symptoms typical of malabsorption, but atypical or subtle clinical manifestations are not rare. The diagnosis must always be made in accordance with current guidelines, based on the finding of serological markers and typical intestinal mucosal alterations detected by upper endoscopic procedure and confirmed with histological examination. Clinical management is based on the strict elimination of gluten from the diet, and a regular monitoring of the nutritional status and the possible occurrence of complications and or associated clinical conditions. In this review we have been described the current evidences on pathogenesis and clinical practice of coeliac disease.

A molecular basis for the T cell response in HLA-DQ2.2 mediated celiac disease

The highly homologous human leukocyte antigen (HLA)-DQ2 molecules, HLA-DQ2.5 and HLA-DQ2.2, are implicated in the pathogenesis of celiac disease (CeD) by presenting gluten peptides to CD4+ T cells. However, while HLA-DQ2.5 is strongly associated with disease, HLA-DQ2.2 is not, and the molecular basis underpinning this differential disease association is unresolved. We here provide structural evidence for how the single polymorphic residue (HLA-DQ2.5-Tyr22α and HLA-DQ2.2-Phe22α) accounts for HLA-DQ2.2 additionally requiring gluten epitopes possessing a serine at the P3 position of the peptide. In marked contrast to the biased T cell receptor (TCR) usage associated with HLA-DQ2.5-mediated CeD, we demonstrate with extensive single-cell sequencing that a diverse TCR repertoire enables recognition of the immunodominant HLA-DQ2.2-glut-L1 epitope. The crystal structure of two CeD patient-derived TCR in complex with HLA-DQ2.2 and DQ2.2-glut-L1 (PFSEQEQPV) revealed a docking strategy, and associated interatomic contacts, which was notably distinct from the structures of the TCR:HLA-DQ2.5:gliadin epitope complexes. Accordingly, while the molecular surfaces of the antigen-binding clefts of HLA-DQ2.5 and HLA-DQ2.2 are very similar, differences in the nature of the peptides presented translates to differences in responding T cell repertoires and the nature of engagement of the respective antigen-presenting molecules, which ultimately is associated with differing disease penetrance.

Innate immunity is a late event in the onset of gliadin-specific enteropathy in the HLA-DQ8 mice

Celiac disease (CD) is a food enteropathy that occurs in genetically susceptible individuals following the ingestion of gluten. Both gluten cytotoxicity and immunity activation play a role in CD pathogenesis; however, the chronological assessment of the different pathogenic mechanisms remains elusive. The models developed so far have only partially addressed this issue. Herein, Ab°DQ8 transgenic mice were administered wheat gliadin and indomethacin for 10 days to induce enteropathy. Gliadin-induced alteration of the small intestinal architecture was associated with increased expression of tissue transglutaminase in the lamina propria and a marked hypoxic environment. Enteropathic mice showed activation of innate immunity, featuring an increase of pro-inflammatory IFN-γ and IL-15 mRNAs, as well as CD11c+CD103+, CD11b+CD11c+, and CD11b+CD103+ dendritic cell subsets. However, the temporal assessment of examined parameters indicated that the induction of innate immunity during the generation of the mucosal lesion, occurred belatedly, highlighting a major role of gliadin intrinsic cytotoxicity in the pathogenic mechanism of this model. These results have important implications for the use of this model to test the impact of biotechnological interventions to reduce the cytotoxicity of gliadin.

Celiac disease: causes, pathology, and nutritional assessment of gluten-free diet. A review

Introduction: celiac patients suffer deficiencies before and during their maintenance of a gluten-free diet. This is due to malabsorption, associated with the disease, and to non-enriched, mostly processed foods high in saturated fats and deficient in the minerals typically present in wheat. Objectives: the main objective of this review was to determine the molecular basis of celiac disease and the nutritional deficiencies that gluten-free diet entails, as well as an assessment of gluten-free diet and its nutritional deficiencies once the intestinal microvilli have been restored. Material and methods: a bibliographic search was carried out through electronic databases. The content of the review focuses on the pathogenesis of celiac disease and the assessment of gluten-free diet when established for treatment. Results: the main deficiencies that occur in untreated celiac patients are (calcium, iron, fiber, folic acid, omega-3, vitamin B12, and vitamin D). It has been observed that the quality of life of celiac patients, after starting treatment, is reduced, and this leads to low adherence to gluten-free diet. In addition, these gluten-free diets without proper follow-up by a nutritionist entail other deficits such as: an increase in the risk of cardiovascular, metabolic, overweight and obesity diseases. Conclusion: gluten-free diet, as followed by celiac patients, usually entails certain deficiencies such as group-B vitamins, vitamin D, calcium, iron, folic acid, and fiber, which is mainly due to the poor nutritional quality of gluten-free products as compared to their equivalents with gluten, and a scarce monitoring by health professionals.

T cell receptor cross-reactivity between gliadin and bacterial peptides in celiac disease.

The human leukocyte antigen (HLA) locus is strongly associated with T cell-mediated autoimmune disorders. HLA-DQ2.5-mediated celiac disease (CeD) is triggered by the ingestion of gluten, although the relative roles of genetic and environmental risk factors in CeD is unclear. Here we identify microbially derived mimics of gliadin epitopes and a parental bacterial protein that is naturally processed by antigen-presenting cells and activated gliadin reactive HLA-DQ2.5-restricted T cells derived from CeD patients. Crystal structures of T cell receptors in complex with HLA-DQ2.5 bound to two distinct bacterial peptides demonstrate that molecular mimicry underpins cross-reactivity toward the gliadin epitopes. Accordingly, gliadin reactive T cells involved in CeD pathogenesis cross-react with ubiquitous bacterial peptides, thereby suggesting microbial exposure as a potential environmental factor in CeD.

MAGI2 Gene Region and Celiac Disease.

Celiac disease (CD) patients present a loss of intestinal barrier function due to structural alterations in the tight junction (TJ) network, the most apical unions between epithelial cells. The association of TJ-related gene variants points to an implication of this network in disease susceptibility. This work aims to characterize the functional implication of TJ-related, disease-associated loci in CD pathogenesis. We performed an association study of 8 TJ-related gene variants in a cohort of 270 CD and 91 non-CD controls. The expression level of transcripts located in the associated SNP region was analyzed by RT-PCR in several human tissues and in duodenal biopsies of celiac patients and non-CD controls. (si)RNA-driven silencing combined with gliadin in the Caco2 intestinal cell line was used to analyze the implication of transcripts from the associated region in the regulation of TJ genes. We replicated the association of rs6962966*A variant [p = 0.0029; OR = 1.88 (95%1.24–2.87)], located in an intron of TJ-related MAGI2 coding gene and upstream of RP4-587D13.2 transcript, bioinformatically classified as a long non-coding RNA (lncRNA). The expression of both genes is correlated and constitutively downregulated in CD intestine. Silencing of lncRNA decreases the levels of MAGI2 protein. At the same time, silencing of MAGI2 affects the expression of several TJ-related genes. The associated region is functionally altered in disease, probably affecting CD-related TJ genes.

Infection, antibiotic exposure, and risk of celiac disease: A systematic review and meta-analysis.

There is evidence of a relationship between infection (and the associated antibiotic exposure) and the risk of celiac disease (CD). This study performed a meta-analysis to investigate this relationship. To identify relevant studies, we conducted systematic searches of the PubMed, Embase, and Cochrane databases for articles published up to April 2019. Random effects models were used to determine overall pooled estimates and 95% confidence intervals (CIs). The meta-analysis included 19 observational studies (15 on infection and six on antibiotic exposure). Our results showed that any infection was associated with an increased risk of CD later in life (odds ratio, 1.37; 95% CI: 1.2-1.56; P < 0.001). The I2 was 94% (high heterogeneity among studies). Subgroup analyses suggested that the risk of CD is not affected by the type of infectious agent, timing of exposure, and site of infection. Exposure to antibiotics was also associated with new-onset CD (odds ratio, 1.2; 95% CI: 1.04-1.39; P < 0.001). Exposure to early infection or antibiotic appears to increase the odds of developing CD, suggesting that intestinal immune or microbiota dysbiosis may play a role in the pathogenesis of CD. These findings may influence clinical management and primary prevention of CD. However, noncausal explanations for these positive associations cannot be excluded.

Çocuk Çölyak Hastalarında Glutensiz Diyet ve Mikrobiyota Odaklı Tedavilerin İntestinal Mikrobiyotaya Etkisi

Çölyak hastalığı genetik yatkınlığı bulunan bireylerde gluten tüketimini izleyen dönemde ciddi gastrointestinal veya ekstraintestinal sistem bozuklukları ile seyreden ince bağırsağın bir hastalığıdır. Hastalığın patogenezinde genetik etmenlerin yanı sıra çevresel faktörlerin rol oynadığı düşünülmektedir. Son yıllarda intestinal mikrobiyotadaki değişimlerin çölyak hastalığının patogenezindeki yeri gösterilmeye ve potansiyel girişimsel olmayan tedaviler için ipuçları sağlanmaya çalışılmaktadır. Yapılan çalışmalar çölyağın aktif ve tedavi altındaki dönemlerinde mikrobiyota değişimleri olduğunu göstermektedir. Ancak, çölyağın tedavisinde kullanılan glutensiz diyetlerin de bu değişimlere katkıda bulunduğuna dair araştırmalar mevcuttur. Dolayısıyla, intestinal mikrobiyotanın modülasyonunda konakçı, diyet ve immün sistem etkileşimlerinin bir arada değerlendirilmesi gerekmektedir. Bu derleme ile çocuk çölyak hastalarında glutensiz diyet ve mikrobiyota odaklı tedavilerin intestinal mikrobiyotaya etkisi incelenmiştir.