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      Host‐microbe interaction in the gastrointestinal tract

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          Summary

          The gastrointestinal tract is a highly complex organ in which multiple dynamic physiological processes are tightly coordinated while interacting with a dense and extremely diverse microbial population. From establishment in early life, through to host‐microbe symbiosis in adulthood, the gut microbiota plays a vital role in our development and health. The effect of the microbiota on gut development and physiology is highlighted by anatomical and functional changes in germ‐free mice, affecting the gut epithelium, immune system and enteric nervous system. Microbial colonisation promotes competent innate and acquired mucosal immune systems, epithelial renewal, barrier integrity, and mucosal vascularisation and innervation. Interacting or shared signalling pathways across different physiological systems of the gut could explain how all these changes are coordinated during postnatal colonisation, or after the introduction of microbiota into germ‐free models. The application of cell‐based in‐vitro experimental systems and mathematical modelling can shed light on the molecular and signalling pathways which regulate the development and maintenance of homeostasis in the gut and beyond.

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          Most cited references145

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          The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems

          The gut-brain axis (GBA) consists of bidirectional communication between the central and the enteric nervous system, linking emotional and cognitive centers of the brain with peripheral intestinal functions. Recent advances in research have described the importance of gut microbiota in influencing these interactions. This interaction between microbiota and GBA appears to be bidirectional, namely through signaling from gut-microbiota to brain and from brain to gut-microbiota by means of neural, endocrine, immune, and humoral links. In this review we summarize the available evidence supporting the existence of these interactions, as well as the possible pathophysiological mechanisms involved. Most of the data have been acquired using technical strategies consisting in germ-free animal models, probiotics, antibiotics, and infection studies. In clinical practice, evidence of microbiota-GBA interactions comes from the association of dysbiosis with central nervous disorders (i.e. autism, anxiety-depressive behaviors) and functional gastrointestinal disorders. In particular, irritable bowel syndrome can be considered an example of the disruption of these complex relationships, and a better understanding of these alterations might provide new targeted therapies.
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            The maternal microbiota drives early postnatal innate immune development.

            Postnatal colonization of the body with microbes is assumed to be the main stimulus to postnatal immune development. By transiently colonizing pregnant female mice, we show that the maternal microbiota shapes the immune system of the offspring. Gestational colonization increases intestinal group 3 innate lymphoid cells and F4/80(+)CD11c(+) mononuclear cells in the pups. Maternal colonization reprograms intestinal transcriptional profiles of the offspring, including increased expression of genes encoding epithelial antibacterial peptides and metabolism of microbial molecules. Some of these effects are dependent on maternal antibodies that potentially retain microbial molecules and transmit them to the offspring during pregnancy and in milk. Pups born to mothers transiently colonized in pregnancy are better able to avoid inflammatory responses to microbial molecules and penetration of intestinal microbes.
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              Functional repair of CFTR by CRISPR/Cas9 in intestinal stem cell organoids of cystic fibrosis patients.

              Single murine and human intestinal stem cells can be expanded in culture over long time periods as genetically and phenotypically stable epithelial organoids. Increased cAMP levels induce rapid swelling of such organoids by opening the cystic fibrosis transmembrane conductor receptor (CFTR). This response is lost in organoids derived from cystic fibrosis (CF) patients. Here we use the CRISPR/Cas9 genome editing system to correct the CFTR locus by homologous recombination in cultured intestinal stem cells of CF patients. The corrected allele is expressed and fully functional as measured in clonally expanded organoids. This study provides proof of concept for gene correction by homologous recombination in primary adult stem cells derived from patients with a single-gene hereditary defect. Copyright © 2013 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                aimee.parker@quadram.ac.uk
                Journal
                Environ Microbiol
                Environ. Microbiol
                10.1111/(ISSN)1462-2920
                EMI
                Environmental Microbiology
                John Wiley and Sons Inc. (Hoboken )
                1462-2912
                1462-2920
                10 November 2017
                July 2018
                : 20
                : 7 ( doiID: 10.1111/emi.2018.20.issue-7 )
                : 2337-2353
                Affiliations
                [ 1 ] Quadram Institute Bioscience Norwich Research Park NR4 7UA UK
                Author notes
                [*] [* ]For Correspondence: E‐mail: aimee.parker@ 123456quadram.ac.uk ; Tel. +44 (0) 1603 255075; Fax +44 (0) 1603 507723.
                [†]

                Joint first authors.

                Article
                EMI13926
                10.1111/1462-2920.13926
                6175405
                28892253
                6e42501f-a4fe-4f61-9bc0-52cdc269f244
                © 2017 The Authors. Environmental Microbiology published by Society for Applied Microbiology and John Wiley & Sons Ltd

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 14 May 2017
                : 25 August 2017
                : 31 August 2017
                Page count
                Figures: 4, Tables: 1, Pages: 17, Words: 12287
                Funding
                Funded by: Biotechnology and Biological Sciences Research Council (BBSRC, UK)
                Funded by: BBSRC
                Award ID: BB/K018256/1
                Funded by: Gut Health and Food Safety
                Award ID: BB/J004529/1
                Funded by: Horizon 2020
                Award ID: H2020‐MSCAIF‐2014; grant 661594
                Categories
                Minireview
                Minireview
                Custom metadata
                2.0
                emi13926
                July 2018
                Converter:WILEY_ML3GV2_TO_NLMPMC version:version=5.5.0 mode:remove_FC converted:08.10.2018

                Microbiology & Virology
                Microbiology & Virology

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