Probiotics Supplements Reduce ER Stress and Gut Inflammation Associated With Gliadin Intake in Celiac Disease Mouse Model (original) (raw)
Related papers
Nutrients, 2021
Exposure to gluten, a protein present in wheat rye and barley, is the major inducer for human Celiac Disease (CD), a chronic autoimmune enteropathy. CD occurs in about 1% worldwide population, in genetically predisposed individuals bearing human leukocyte antigen (HLA) DQ2/DQ8. Gut epithelial cell stress and the innate immune activation are responsible for the breaking oral tolerance to gliadin, a gluten component. To date, the only treatment available for CD is a long-term gluten-free diet. Several studies have shown that an altered composition of the intestinal microbiota (dysbiosis) could play a key role in the pathogenesis of CD through the modulation of intestinal permeability and the regulation of the immune system. Here, we show that gliadin induces a chronic endoplasmic reticulum (ER) stress condition in the small intestine of a gluten-sensitive mouse model and that the coadministration of probiotics efficiently attenuates both the unfolded protein response (UPR) and gut inf...
Gut Microbiota in Celiac Disease: Is There Any Role for Probiotics?
Frontiers in Immunology, 2020
Celiac disease (CD) is an immune-mediated disorder initiated by the ingestion of gluten in genetically predisposed individuals. Recent data shows that changes in the gut microbiome composition and function are linked with chronic inflammatory diseases; this might also be the case for CD. The main aim of this manuscript is to discuss our present knowledge of the relationships between gut microbiota alterations and CD and to understand if there is any role for probiotics in CD therapy. PubMed was used to search for all of the studies published from November 2009 to November 2019 using key words such as "Celiac Disease" and "Microbiota" (306 articles), "Celiac Disease" and "Gastrointestinal Microbiome" (139), and "Probiotics" and "Celiac Disease" (97 articles). The search was limited to articles published in English that provided evidence-based data. Literature analysis showed that the gut microbiota has a well-established role in gluten metabolism, in modulating the immune response and in regulating the permeability of the intestinal barrier. Promising studies suggest a possible role of probiotics in treating and/or preventing CD. Nevertheless, human trials on the subject are still scarce and lack homogeneity. A possible role was documented for probiotics in improving CD-related symptoms, modulating the peripheral immune response and altering the fecal microbiota, although the results were not consistent in all of the studies. No evidence was found that probiotic administration might prevent CD onset. Knowledge of the role of intestinal bacteria in the development of CD opens new possibilities for its treatment through probiotic administration, even though further studies are needed to better clarify whether probiotics can help treat or prevent the disease and to define which probiotics to use, at what dose and for how long.
The Gut Microbiota in Celiac Disease and probiotics
Nutrients, 2019
Celiac disease (CeD) is an immune-mediated enteropathy, and unique in that the specific trigger is known: gluten. The current mainstay of therapy is a gluten-free diet (GFD). As novel therapies are being developed, complementary strategies are also being studied, such as modulation of the gut microbiome. The gut microbiota is involved in the initiation and perpetuation of intestinal inflammation in several chronic diseases. Intestinal dysbiosis has been reported in CeD patients, untreated or treated with GFD, compared to healthy subjects. Several studies have identified differential bacterial populations associated with CeD patients and healthy subjects. However, it is still not clear if intestinal dysbiosis is the cause or effect of CeD. Probiotics have also been considered as a strategy to modulate the gut microbiome to an anti-inflammatory state. However, there is a paucity of data to support their use in treating CeD. Further studies are needed with therapeutic microbial formula...
Frontiers in Microbiology, 2018
Celiac disease (CD) is an autoimmune disorder of the small intestine, caused by gluten induced inflammation in some individuals susceptible to genetic and environmental influences. To date, pathophysiology of CD in relation to intestinal microbiota is not known well. This review relies on contribution of intestinal microbiome and oral microbiome in pathogenesis of CD based on their interactions with gluten, thereby highlighting the role of upper gastrointestinal microbiota. It has been hypothesized that CD might be triggered by additive effects of immunotoxic gluten peptides and intestinal dysbiosis (microbial imbalance) in the people with or without genetic susceptibilities, where antibiotics may be deriving dysbiotic agents. In contrast to the intestinal dysbiosis, genetic factors even seem secondary in disease outcome thus suggesting the importance of interaction between microbes and dietary factors in immune regulation at intestinal mucosa. Moreover, association of imbalanced counts of some commensal microbes in intestine of CD patients suggests the scope for probiotic therapies. Lactobacilli and specific intestinal and oral bacteria are potent source of gluten degrading enzymes (glutenases) that may contribute to commercialization of a novel glutenase therapy. In this review, we shall discuss advantages and disadvantages of food based therapies along with probiotic therapies where probiotic therapies are expected to emerge as the safest biotherapies among other in-process therapies. In addition, this review emphasizes on differential targets of probiotics that make them suitable to manage CD as along with glutenase activity, they also exhibit immunomodulatory and intestinal microbiome modulatory properties.
Laboratory Investigation, 2012
Coeliac disease (CD) is a malabsorptive enteropathy resulting from intolerance to gluten. Environmental factors and the microbiota are suggested to have critical roles in the onset of CD. The CD71 IgA receptor on epithelial cells is responsible for abnormal retrotranscytosis of IgA-gluten peptide complexes from the intestinal lumen into the lamina propria, inducing intestinal inflammation. However, understanding the role of gluten in the CD physiopathology has been hindered by the absence of relevant animal models. Here, we generated a mouse model for CD to study the factors controlling its pathogenesis as well as to investigate the influence of oral delivery of probiotics on disease development. Gluten sensitivity was established by feeding three generations of BALB/c mice a gluten-free diet (GÀ) followed by gluten challenge (G þ) for 30 days. The G þ mice developed villous atrophy, crypt hyperplasia and infiltration of T cells and macrophages in the small intestine. Inflammation was associated with an overexpression of CD71 on the apical side of enterocytes and an increase of plasma cells producing IgA, which colocalised with the CD71. Moreover, IgA colocalised with the transglutaminase 2 (TG2), the production of which was increased in the lamina propria of G þ mice. These mice displayed increased production of cyclooxygenase-2 (COX-2), pro-inflammatory cytokines and IL-15, as well as anti-gliadin and anti-TG2 autoantibodies. The commensal flora-isolated presumptive probiotic Saccharomyces boulardii KK1 strain hydrolysed the 28-kDa a-gliadin fraction, and its oral delivery in G þ mice improved enteropathy development in association with decrease of epithelial cell CD71 expression and local cytokine production. In conclusion, the G þ BALB/c mouse represents a new mouse model for human CD based on histopathological features and expression of common biomarkers. The selected probiotic treatment reversing disease development will allow the study of the role of probiotics as a new therapeutic approach of CD.
Intestinal Microbiota Modulates Gluten-Induced Immunopathology in Humanized Mice
The American journal of pathology, 2015
Celiac disease (CD) is an immune-mediated enteropathy triggered by gluten in genetically susceptible individuals. The recent increase in CD incidence suggests that additional environmental factors, such as intestinal microbiota alterations, are involved in its pathogenesis. However, there is no direct evidence of modulation of gluten-induced immunopathology by the microbiota. We investigated whether specific microbiota compositions influence immune responses to gluten in mice expressing the human DQ8 gene, which confers moderate CD genetic susceptibility. Germ-free mice, clean specific-pathogen-free (SPF) mice colonized with a microbiota devoid of opportunistic pathogens and Proteobacteria, and conventional SPF mice that harbor a complex microbiota that includes opportunistic pathogens were used. Clean SPF mice had attenuated responses to gluten compared to germ-free and conventional SPF mice. Germ-free mice developed increased intraepithelial lymphocytes, markers of intraepithelial...
Nutrients
Celiac disease (CD) is an autoimmune enteropathy caused by an intolerance to gluten proteins. It has been hypothesized that probiotic bacteria may exert beneficial effects by modulating inflammatory processes and by sustaining peptide hydrolysis at the intestinal level. This study aims at evaluating the capacity of a probiotic mixture (two different strains of lactobacilli and three of bifidobacteria) to hydrolyze gluten peptides following simulated gastrointestinal digestion of gliadin (PT-gliadin). The capacity of bacterial hydrolysates to counteract the toxic effects of gliadin-derived peptides in Caco-2 cells was also assessed. The protein and peptide mixtures, untreated or proteolyzed with the probiotic preparation, were analyzed before and after each proteolytic step with different techniques (SDS-PAGE, reverse phase HPLC, filtration on different molecular cut-off membranes). These experiments demonstrated that PT-gliadin can be further digested by bacteria into lower molecula...
Probiotics and the Microbiome in Celiac Disease: A Randomised Controlled Trial
Evidence-based complementary and alternative medicine : eCAM, 2016
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...
Probiotics in Childhood Celiac Disease
Probiotics and Prebiotics in Human Nutrition and Health, 2016
Celiac disease (CD) is an autoimmune enteropathy induced by gluten ingestion in genetically susceptible individuals. Genetic predisposition plays an important role in the development of CD, but it is not sufficient by itself for the disease development. Although gluten proteins are the main environmental factor involved in CD pathogenesis and ingestion of gluten is necessary to manifest the disease, recent studies have suggested that alteration of the microbiota could be involved and, in particular, the interplay between gut microbiota and the mucosal immune system. Dysbiosis, the alteration of the microbiota, has been associated with a variety of intestinal pathologies including Crohn disease and CD. Most observational studies in children and adults with CD have shown alterations in the intestinal microbiota composition compared to control subjects, which is only partially recovered after treatment with a gluten-free diet (GFD). At this time, the only treatment for CD is lifelong adherence to a GFD, which involves the elimination of grains containing gluten, wheat, rye, and barley. However, it is difficult for many patients to follow a GFD. Abnormalities in the gut microbiome in CD patients have led to the use of probiotics as a promising alternative as a therapeutic or preventative approach.