The microbiome as a possible target to prevent celiac disease.
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ABSTRACT:
SUBMITTER: Leonard MM
PROVIDER: S-EPMC5278927 | biostudies-literature | 2016
REPOSITORIES: biostudies-literature
Publications
The microbiome as a possible target to prevent celiac disease.
Leonard Maureen M MM Fasano Alessio A
Expert review of gastroenterology & hepatology 20160401 5
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Project description: Not available
| S-EPMC11842898 | biostudies-literature
Project description:Background. There is limited research investigating the composition of the gastrointestinal microbiota in individuals with celiac disease (CoeD) reporting only partial symptom improvement despite adherence to a strict gluten-free diet (GFD). The aim of this research was to determine if the gastrointestinal microbiota could be altered by probiotic bacteria and provide a potential new therapy for this subgroup. Methods. A multicentre RCT was conducted between January and August 2011 in Australia. Participants included 45 people with CoeD reporting only partial symptom improvement despite adherence to a strict GFD for a minimum of 12 months. Participants took 5?g of VSL#™ probiotic formulation (n = 23) or 5?g placebo (n = 22) orally twice daily for 12 weeks. The main outcome measured was the efficacy of the probiotic formula in altering faecal microbiota counts between baseline and week 12. Safety was determined by safety blood and monitoring adverse events. Results. SPSS™ multivariate repeated measures analysis (95th confidence level) revealed no statistically significant changes between the groups in the faecal microbiota counts or blood safety measures over the course of the study. Conclusion. The probiotic formula when taken orally over the 12-week period did not significantly alter the microbiota measured in this population. The trial was registered with Australian and New Zealand Clinical Trials Register ACTRN12610000630011.
| S-EPMC4972910 | biostudies-other
Project description:Beside skeletal system maintenance and protection, possible extra-calcium roles of vitamin D have been recently described. In particular, studies have investigated possible roles of vitamin D as a key modulator of inflammation and immune mechanisms and of the intestinal mucosa barrier. In this regard, vitamin D has been considered as a factor that affects different conditions such as immune-mediated diseases. The new emerging role of vitamin D and its involvement in immune modulation has led it to be considered as a possible key factor involved in celiac disease (CD) onset. CD is a chronic immune-mediated enteropathy of the small intestine that is triggered by dietary gluten protein exposure in individuals who are genetically predisposed. However, along with gluten, other environmental factors are also involved in CD onset. The renewed interest in a molecule that offers great possibilities for new roles has led to an increase in studies, although there remains a lack of studies aimed at contextualizing the role of vitamin D on CD. This review aims to define the possible role of vitamin D in CD onset as it is presently understood, taking into account potential links among vitamin D, the immune system and CD.
| S-EPMC7231074 | biostudies-literature
Project description:Composition and functional variation in gut microbiome of celiac disease patients and first-degree relatives
| PRJEB5780 | ENA
Project description:A higher intake of gluten during childhood is associated with increased risk of celiac disease, and the incidence of celiac disease peaks shortly after the time point when associations with higher gluten intake during the second and third year of life occur. Additional environmental factors are most likely necessary for celiac disease to develop. It is hypothesized that gastrointestinal infections increase gut permeability and exposure to gluten. Alternatively, infections may lead to gut dysbiosis and chronic inflammation, with leakage of self-antigens that mimic gluten peptides that leads to an autoimmune-like response. Different gluten interventions to prevent celiac disease have been proposed. Early clinical studies suggested an optimal time point introducing gluten between 4 and 6 months of age while the infant is being breastfed. However, later clinical trials on reduced gluten intake given to infants have shown no protection from celiac disease if gluten introduction was delayed or if gluten was introduced in small amounts during the child's first year of life. Still, more randomized clinical trials (RCTs) are warranted to answer the question if a reduced amount of gluten, not only at the time of introduction during infancy but also in a longer time frame, will prevent children at genetic risk from having lifelong celiac disease. It needs to be clarified whether dietary interventions are effective strategies to be proposed as future prevention of celiac disease in the general population. The present mini-review provides an overview of ongoing or completed RCTs that have focused on interventions during early childhood with the aim of preventing celiac disease.
| S-EPMC9992640 | biostudies-literature
Project description:In the past it was believed that genetic predisposition and exposure to gluten were necessary and sufficient to develop celiac disease (CD). Recent studies however suggest that loss of gluten tolerance can occur at any time in life as a consequence of other environmental stimuli. Many environmental factors known to influence the composition of the intestinal microbiota are also suggested to play a role in the development of CD. These include birthing delivery mode, infant feeding, and antibiotic use. To date no large-scale longitudinal studies have defined if and how gut microbiota composition and metabolomic profiles may influence the loss of gluten tolerance and subsequent onset of CD in genetically-susceptible individuals. Here we describe a prospective, multicenter, longitudinal study of infants at risk for CD which will employ a blend of basic and applied studies to yield fundamental insights into the role of the gut microbiome as an additional factor that may play a key role in early steps involved in the onset of autoimmune disease.
| S-EPMC4663598 | biostudies-literature
Project description:Celiac disease and inflammatory bowel disease including ulcerative colitis (UC) and Crohn's disease are both immune-mediated enteropathies. It is rare for both celiac disease and inflammatory bowel disease to occur together in an individual patient. This association has been reported in adults, however, very rarely in children. Here, we report an unusual case of an 8-year-old child with a history of anemia and failure to thrive who presented with bloody diarrhea. His evaluation showed anemia, elevated inflammatory markers, and positive celiac antibodies. Endoscopic evaluation revealed partial duodenal villous atrophy and pancolitis. He was diagnosed with celiac disease and UC and responded well to a gluten-free diet and steroid/mesalamine therapy. The patient's genetic testing revealed markers showing susceptibility for both celiac disease and UC. It is important to be aware of this association as both conditions can present with similar clinical features, however, require different therapeutic approaches.
| S-EPMC4425271 | biostudies-literature
Project description:The role of B cells and posttranslational modifications in pathogenesis of organ-specific immune diseases is increasingly envisioned but remains poorly understood, particularly in human disorders. In celiac disease, transglutaminase 2-modified (TG2-modified; deamidated) gluten peptides drive disease-specific T cell and B cell responses, and antibodies to deamidated gluten peptides are excellent diagnostic markers. Here, we substantiate by high-throughput sequencing of IGHV genes that antibodies to a disease-specific, deamidated, and immunodominant B cell epitope of gluten (PLQPEQPFP) have biased and stereotyped usage of IGHV3-23 and IGHV3-15 gene segments with modest somatic mutations. X-ray crystal structures of 2 prototype IGHV3-15/IGKV4-1 and IGHV3-23/IGLV4-69 antibodies reveal peptide interaction mainly via germline-encoded residues. In-depth mutational analysis showed restricted selection and substitution patterns at positions involved in antigen binding. While the IGHV3-15/IGKV4-1 antibody interacts with Glu5 and Gln6, the IGHV3-23/IGLV4-69 antibody interacts with Gln3, Pro4, Pro7, and Phe8 - residues involved in substrate recognition by TG2. Hence, both antibodies, despite different interaction with the epitope, recognize signatures of TG2 processing that facilitates B cell presentation of deamidated gluten peptides to T cells, thereby providing a molecular framework for the generation of these clinically important antibodies. The study provides essential insight into the pathogenic mechanism of celiac disease.
| S-EPMC5621872 | biostudies-literature
Project description:Cystic fibrosis (CF) is a disease caused by loss-of-function mutations affecting the CF transmembrane conductance regulator (CFTR), a chloride channel. Recent evidence indicates that CFTR is inhibited by a gluten/gliadin-derived peptide (P31-43), causing an acquired state of CFTR inhibition within the gut that contributes to the pathogenesis of celiac disease (CD). Of note, CFTR inhibition does not only cause intra- and extracellular ion imbalances but also affects proteostasis by activating transglutaminase-2 (TGM2) and by disabling autophagy. These three phenomena (CFTR inhibition, TGM2 activation, and autophagy impairment) engage in multiple self-amplifying circuitries, thus forming an "infernal trio". The trio hinders enterocytes from returning to homeostasis and instead locks them in an irreversible pro-inflammatory state that ultimately facilitates T lymphocyte-mediated immune responses against another gluten/gliadin-derived peptide (P57-68), which,upon deamidation by activated TGM2, becomes fully antigenic. Hence, the pathogenic protein gliadin exemplifies a food constituent the exceptional immunogenicity of which arises from a combination of antigenicity (conferred by deaminated P57-68) and adjuvanticity (conferred by P31-43). CF can be treated by agents targeting the "infernal trio" including CFTR potentiators, TGM2 inhibitors, and autophagy enhancers. We speculate that such agents may also be used for CD therapy and indeed could constitute close-to-etiological treatments of this enteropathy.
| S-EPMC6368542 | biostudies-literature
Project description:IntroductionCeliac disease (CD) may be associated with gut microbial dysbiosis. Whether discrete gluten exposure in subjects with well-controlled disease on a gluten-free diet impacts the gut microbiome is unknown and may have implications for understanding disease activity and symptoms. We conducted a prospective study to evaluate the impact of gluten exposure on the gut microbiome in patients with CD and nonceliac gluten sensitivity (NCGS).MethodsSubjects with CD (n = 9) and NCGS (n = 8) previously on a gluten-free diet were administered a 14-day gluten challenge (5 g of gluten per day) and compared with controls (n = 8) on a usual gluten-containing diet. Stool was collected for fecal microbiome analysis using 16S rRNA gene and metagenomic sequencing before, during, and after the gluten challenge. Symptoms were assessed using 2 validated clinical scales.ResultsAmong subjects with CD and NCGS, there were no significant fecal microbial changes in response to gluten challenge. Gut microbiome composition differed among controls, subjects with CD, and subjects with NCGS at baseline, and these differences persisted despite gluten exposure. Gastrointestinal and general health symptoms reported by subjects with CD and NCGS were worst in the middle of gluten challenge and lessened by its end, with no consistent associations with gut microbiome composition.DiscussionPre-existing fecal microbiome diversity was unaffected by gluten challenge in adult subjects with CD and NCGS. These findings suggest that current microbiome status is unrelated to current disease activity and disease severity.
| S-EPMC8691493 | biostudies-literature