Probiotics can reduce immunotoxic effects of gliadin

2012, Feb. Bifidobacterium longum CECT 7347 modulates immune responses in a gliadin-induced enteropathy animal model.  Laparra JM, Olivares M, Gallina O, Sanz Y. (J Proteomics. 2012 Dec 21) Institute of Agrochemistry and Food Technology, National Research Council, IATA-CSIC, Valencia, Spain.[PLoS One. 2012] Abstract:  In this study, we hypothesise that the administration of Bifidobacterium longum CECT 7347, previously selected for reducing gliadin immunotoxic effects in vitro, could exert protective effects in an animal model of gliadin-induced enteropathy. The effects of this bacterium were evaluated in newborn rats fed gliadin alone or sensitised with interferon (IFN)-γ and fed gliadin. Jejunal tissue sections were collected for histological, NFκB mRNA expression and cytokine production analyses. Leukocyte populations and T-cell subsets were analysed in peripheral blood samples. The possible translocation of the bacterium to different organs was determined by plate counting and the composition of the colonic microbiota was quantified by real-time PCR. Feeding gliadin alone reduced enterocyte height and peripheral CD4+ cells, but increased CD4+/Foxp3+ T and CD8+ cells, while the simultaneous administration of B. longum CECT 7347 exerted opposite effects. Animals sensitised with IFN-γ and fed gliadin showed high cellular infiltration, reduced villi width and enterocyte height. Sensitised animals also exhibited increased NFκB mRNA expression and TNF-α production in tissue sections. B. longum CECT 7347 administration increased NFκB expression and IL-10, but reduced TNF-α, production in the enteropathy model. In sensitised gliadin-fed animals, CD4+, CD4+/Foxp3+ and CD8+ T cells increased, whereas the administration of B. longum CECT 7347 reduced CD4+ and CD4+/Foxp3+ cell populations and increased CD8+ T cell populations. The bifidobacterial strain administered represented between 75-95% of the total bifidobacteria isolated from all treated groups, and translocation to organs was not detected. These findings indicate that B. longum attenuates the production of inflammatory cytokines and the CD4+ T-cell mediated immune response in an animal model of gliadin-induced enteropathy. 

2012, Feb.  Early Life Nutrition and HLA-DQ genotype Have a Combined Influence on the Composition of the Intestinal Microflora, Immune System Development and Sensitivity to Gluten“…could it be that alterations in the environment during the early life of genetically predisposed individuals leads to imbalanced microflora development and immune response to environmental antigens, like gluten, leading to imbalanced physiology? Hold that thought while we discuss this revolutionary study…As you know, Human Leukocyte Antigen (HLA)-DQ genes are the major genetic risk factors in celiac disease. What was not fully understood prior to this recent study was how HLA-DQ genotype influences composition of gut microbiota in infants (2)…Giada De Palma and her Spanish researcher team assessed both HLA-genotype and faecal microbiota (using quantitative PCR) of 146 healthy infants during their first 4 months of life(1). The infants were clustered into two broad groups- breast feeding VS formula feeding- and then were further clustered by into three groups based on HLA-DQ genotype, stratifying for High, Intermediate and Low genetic risk for celiac disease.  They found that irrespective of milk-feeding type, HLA-DQ genotype influenced the composition of the infant gut microbiota. Specifically the gut microbiota of infants with low genetic risk contained higher levels of species in the Bifidobacterium group, particularly Bifidobacterium longum. Conversely the microbiota of those with high genetic risk contained less Bifidobacterium species and more Staphylococcus species…What are mechanisms and clinical implications? Due to the fact that HLA class II molecules are largely expressed on lamina propria dentritic cells (DCs)- professional antigen presenting cells (APCs)- genetic variants in HLA-DQ contribute to the magnitude of innate immune system activation upon exposure to microbial and food antigens in the gut lumen.” MIke Mutzel 

2011, Oct.   Immunomodulatory effects of lactobacillus casei administration in a mouse model of gliadin-sensitive enteropathy. D’Arienzo R., Stefanile R., Maurano F., Mazzarella G., Ricca E., Troncone R., Auricchio S., Rossi M. Scand. J. Immunol. 2011;74:335–341. doi: 10.1111/j.1365-3083.2011.02582.x. [PubMedConclusion: the administration of probiotic strain induced a complete recovery of villus blunting. This finding was associated with a delay in weight decrease and a recovery of basal TNF-α levels, whereas the numbers of CD25(+) cells and the levels of IL-2 remained unchanged. 

2010, Jan. De Palma G, Capilla A, Nadal I, Nova E, Pozo T, et al. (2010) Interplay 
Between Human Leukocyte Antigen Genes and the Microbial Colonization Process of the Newborn Intestine. Current Issues in Molecular Biology 12: 1–10. 

2008, Nov. Bifidobacterium strains suppress in vitro the pro-inflammatory milieu triggered by the large intestinal microbiota of coeliac patients Marcela Medina1, Giada De Palma1, Carmen Ribes-Koninckx2, Microbial Ecophysiology and Nutrition, Instituto de Agroquímica y Tecnología de Alimentos (CSIC), Apartado 73, 46100 Burjassot, Valencia, Spain, Journal of Inflammation Nov. 2008 Results: Bifidobacterium strains suppressed the pro-inflammatory cytokine pattern induced by the large intestinal content of CD patients and increased IL-10 production. Cytokine effects induced by faecal microbiota seemed to be mediated by the NFκB pathway. Conclusion: The intestinal microbiota of CD patients could contribute to the Th1 pro- inflammatory milieu characteristic of the disease, while B. longum ES1 and B. bifidum ES2 could reverse these deleterious effects. These findings hold future perspectives of interest in CD therapy. 

2008, June Live probiotic Bifidobacterium lactis bacteria inhibit the toxic effects induced by wheat gliadin in epithelial cell culture, K Lindfors,* T Blomqvist,* K Juuti-Uusitalo,* S Stenman,* J Venäläinen, M Mäki,* and K Kaukinen, Paediatric Research Centre, Medical School, University of Tampere, Finland, Department of Peadiatrics, Tampere University Hospital, Tampere, Finland, Clin Exp Immunol. 2008 June Conclusion: We conclude thus that live B. lactis bacteria can counteract directly the harmful effects exerted by coeliac-toxic gliadin and would clearly warrant further studies of its potential as a novel dietary supplement in the treatment of coeliac disease. .


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