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      Immunological mechanisms underpinning faecal microbiota transplantation for the treatment of inflammatory bowel disease

      1 , 2 , 3 , 1 , 3 , 1 , 2 , 4 , 1 , 2 , 3
      Clinical & Experimental Immunology
      Wiley

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          Abstract

          Inflammatory bowel disease (IBD) is a chronic gastrointestinal disease that results from a dysregulated immune response against specific environmental triggers in a genetically predisposed individual. Increasing evidence has indicated a causal role for changes in gut microbiota (dysbiosis) contributing to this immune-mediated intestinal inflammation. These mechanisms involve dysregulation of multiple facets of the host immune pathways that are potentially reversible. Faecal microbiota transplantation (FMT) is the transfer of processed stool from a healthy donor into an individual with an illness. FMT has shown promising results in both animal model experiments and clinical studies in IBD in the resolution of intestinal inflammation. The underlying mechanisms, however, are unclear. Insights from these studies have shown interactions between modulation of dysbiosis via changes in abundances of specific members of the gut microbial community and changes in host immunological pathways. Unravelling these causal relationships has promising potential for a translational therapy role to develop targeted microbial therapies and understand the mechanisms that underpin IBD aetiopathogenesis. In this review, we discuss current evidence for the contribution of gut microbiota in the disruption of intestinal immune homeostasis and immunoregulatory mechanisms that are associated with the resolution of inflammation through FMT in IBD.

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          Inflammatory bowel disease.

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            A microbial symbiosis factor prevents intestinal inflammatory disease.

            Humans are colonized by multitudes of commensal organisms representing members of five of the six kingdoms of life; however, our gastrointestinal tract provides residence to both beneficial and potentially pathogenic microorganisms. Imbalances in the composition of the bacterial microbiota, known as dysbiosis, are postulated to be a major factor in human disorders such as inflammatory bowel disease. We report here that the prominent human symbiont Bacteroides fragilis protects animals from experimental colitis induced by Helicobacter hepaticus, a commensal bacterium with pathogenic potential. This beneficial activity requires a single microbial molecule (polysaccharide A, PSA). In animals harbouring B. fragilis not expressing PSA, H. hepaticus colonization leads to disease and pro-inflammatory cytokine production in colonic tissues. Purified PSA administered to animals is required to suppress pro-inflammatory interleukin-17 production by intestinal immune cells and also inhibits in vitro reactions in cell cultures. Furthermore, PSA protects from inflammatory disease through a functional requirement for interleukin-10-producing CD4+ T cells. These results show that molecules of the bacterial microbiota can mediate the critical balance between health and disease. Harnessing the immunomodulatory capacity of symbiosis factors such as PSA might potentially provide therapeutics for human inflammatory disorders on the basis of entirely novel biological principles.
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              The microbiome and innate immunity.

              The intestinal microbiome is a signalling hub that integrates environmental inputs, such as diet, with genetic and immune signals to affect the host's metabolism, immunity and response to infection. The haematopoietic and non-haematopoietic cells of the innate immune system are located strategically at the host-microbiome interface. These cells have the ability to sense microorganisms or their metabolic products and to translate the signals into host physiological responses and the regulation of microbial ecology. Aberrations in the communication between the innate immune system and the gut microbiota might contribute to complex diseases.
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                Author and article information

                Journal
                Clinical & Experimental Immunology
                Clin Exp Immunol
                Wiley
                0009-9104
                1365-2249
                November 27 2019
                January 2020
                November 27 2019
                January 2020
                : 199
                : 1
                : 24-38
                Affiliations
                [1 ]Centre for Liver and Gastroenterology Research NIHR Birmingham Biomedical Research Centre University of Birmingham Birmingham UK
                [2 ]Department of Gastroenterology Queen Elizabeth Hospital University Hospitals Birmingham Birmingham UK
                [3 ]University of Birmingham Microbiome Treatment Centre University of Birmingham Birmingham UK
                [4 ]Liver Transplant and Hepatobiliary Unit Queen Elizabeth Hospital University Hospitals Birmingham Birmingham UK
                Article
                10.1111/cei.13397
                6904658
                31777058
                85de34a1-aa21-460d-9a4b-ed81f4649ae3
                © 2020

                http://onlinelibrary.wiley.com/termsAndConditions#vor

                http://doi.wiley.com/10.1002/tdm_license_1.1

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