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      Gut microbiome-host interactions in health and disease

      review-article
      1 , 1 , 2 ,
      Genome Medicine
      BioMed Central

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          Abstract

          The gut microbiome is the term given to describe the vast collection of symbiotic microorganisms in the human gastrointestinal system and their collective interacting genomes. Recent studies have suggested that the gut microbiome performs numerous important biochemical functions for the host, and disorders of the microbiome are associated with many and diverse human disease processes. Systems biology approaches based on next generation 'omics' technologies are now able to describe the gut microbiome at a detailed genetic and functional (transcriptomic, proteomic and metabolic) level, providing new insights into the importance of the gut microbiome in human health, and they are able to map microbiome variability between species, individuals and populations. This has established the importance of the gut microbiome in the disease pathogenesis for numerous systemic disease states, such as obesity and cardiovascular disease, and in intestinal conditions, such as inflammatory bowel disease. Thus, understanding microbiome activity is essential to the development of future personalized strategies of healthcare, as well as potentially providing new targets for drug development. Here, we review recent metagenomic and metabonomic approaches that have enabled advances in understanding gut microbiome activity in relation to human health, and gut microbial modulation for the treatment of disease. We also describe possible avenues of research in this rapidly growing field with respect to future personalized healthcare strategies.

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          Most cited references64

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          Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis.

          Toll-like receptors (TLRs) play a crucial role in host defense against microbial infection. The microbial ligands recognized by TLRs are not unique to pathogens, however, and are produced by both pathogenic and commensal microorganisms. It is thought that an inflammatory response to commensal bacteria is avoided due to sequestration of microflora by surface epithelia. Here, we show that commensal bacteria are recognized by TLRs under normal steady-state conditions, and this interaction plays a crucial role in the maintenance of intestinal epithelial homeostasis. Furthermore, we find that activation of TLRs by commensal microflora is critical for the protection against gut injury and associated mortality. These findings reveal a novel function of TLRs-control of intestinal epithelial homeostasis and protection from injury-and provide a new perspective on the evolution of host-microbial interactions.
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            An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system.

            The mammalian gastrointestinal tract harbors a complex ecosystem consisting of countless bacteria in homeostasis with the host immune system. Shaped by evolution, this partnership has potential for symbiotic benefit. However, the identities of bacterial molecules mediating symbiosis remain undefined. Here we show that, during colonization of animals with the ubiquitous gut microorganism Bacteroides fragilis, a bacterial polysaccharide (PSA) directs the cellular and physical maturation of the developing immune system. Comparison with germ-free animals reveals that the immunomodulatory activities of PSA during B. fragilis colonization include correcting systemic T cell deficiencies and T(H)1/T(H)2 imbalances and directing lymphoid organogenesis. A PSA mutant of B. fragilis does not restore these immunologic functions. PSA presented by intestinal dendritic cells activates CD4+ T cells and elicits appropriate cytokine production. These findings provide a molecular basis for host-bacterial symbiosis and reveal the archetypal molecule of commensal bacteria that mediates development of the host immune system.
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              Commensal host-bacterial relationships in the gut.

              One potential outcome of the adaptive coevolution of humans and bacteria is the development of commensal relationships, where neither partner is harmed, or symbiotic relationships, where unique metabolic traits or other benefits are provided. Our gastrointestinal tract is colonized by a vast community of symbionts and commensals that have important effects on immune function, nutrient processing, and a broad range of other host activities. The current genomic revolution offers an unprecedented opportunity to identify the molecular foundations of these relationships so that we can understand how they contribute to our normal physiology and how they can be exploited to develop new therapeutic strategies.
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                Author and article information

                Journal
                Genome Med
                Genome Medicine
                BioMed Central
                1756-994X
                2011
                4 March 2011
                4 March 2012
                : 3
                : 3
                : 14
                Affiliations
                [1 ]Section of Biosurgery and Surgical Technology, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, 10th Floor, QEQM, St Mary's Hospital, London W2 1NY, UK
                [2 ]Section of Bimolecular Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, The Sir Alexander Fleming Building, South Kensington, London SW7 2AZ, UK
                Article
                gm228
                10.1186/gm228
                3092099
                21392406
                59bb606f-fc65-48a7-8ab6-489c25360e29
                Copyright ©2011 BioMed Central Ltd
                History
                Categories
                Review

                Molecular medicine
                Molecular medicine

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