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      The intestinal barrier in multiple sclerosis: implications for pathophysiology and therapeutics

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          Abstract

          Increasing evidence suggests that there is intestinal barrier dysfunction in multiple sclerosis. Camara-Lemarroy et al. address the mechanisms by which an altered intestinal barrier could lead to an altered neuroinflammatory response, and discuss the potential of barrier-stabilizing strategies as novel therapeutic avenues in multiple sclerosis.

          Abstract

          Biological barriers are essential for the maintenance of homeostasis in health and disease. Breakdown of the intestinal barrier is an essential aspect of the pathophysiology of gastrointestinal inflammatory diseases, such as inflammatory bowel disease. A wealth of recent studies has shown that the intestinal microbiome, part of the brain-gut axis, could play a role in the pathophysiology of multiple sclerosis. However, an essential component of this axis, the intestinal barrier, has received much less attention. In this review, we describe the intestinal barrier as the physical and functional zone of interaction between the luminal microbiome and the host. Besides its essential role in the regulation of homeostatic processes, the intestinal barrier contains the gut mucosal immune system, a guardian of the integrity of the intestinal tract and the whole organism. Gastrointestinal disorders with intestinal barrier breakdown show evidence of CNS demyelination, and content of the intestinal microbiome entering into the circulation can impact the functions of CNS microglia. We highlight currently available studies suggesting that there is intestinal barrier dysfunction in multiple sclerosis. Finally, we address the mechanisms by which commonly used disease-modifying drugs in multiple sclerosis could alter the intestinal barrier and the microbiome, and we discuss the potential of barrier-stabilizing strategies, including probiotics and stabilization of tight junctions, as novel therapeutic avenues in multiple sclerosis.

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          Author and article information

          Journal
          Brain
          Brain
          brainj
          Brain
          Oxford University Press
          0006-8950
          1460-2156
          July 2018
          30 May 2018
          01 July 2019
          : 141
          : 7
          : 1900-1916
          Affiliations
          [1 ]Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
          [2 ]Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
          [3 ]Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
          [4 ]Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
          Author notes
          Correspondence to: Carlos R. Camara-Lemarroy, MS Clinic, FMC and University of Calgary, 1403 29 Street NW, T2N 2T9, Calgary, Alberta, Canada, E-mail: Carlos.Camara-Lemarroy@ 123456albertahealthservices.ca
          Article
          PMC6022557 PMC6022557 6022557 awy131
          10.1093/brain/awy131
          6022557
          29860380
          472fa848-44a0-4832-b338-b0110968fdcc
          © The Author(s) (2018). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com

          This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model ( https://academic.oup.com/journals/pages/about_us/legal/notices)

          History
          : 1 December 2017
          : 28 February 2018
          : 24 March 2018
          Page count
          Pages: 17
          Funding
          Funded by: Hotchkiss Brain Institute
          Funded by: Canada Research Chair
          Funded by: Canadian Institutes of Health Research 10.13039/501100000024
          Funded by: Multiple Sclerosis Society of Canada 10.13039/501100000261
          Funded by: Alberta Innovates – Health Solutions CRIO Team program
          Categories
          Review Articles

          inflammatory bowel disease,disease-modifying therapies,microbiota,intestinal barrier,multiple sclerosis

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