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Neurotherapeutics. 2018 Jan;15(1):68-74. doi: 10.1007/s13311-017-0582-3.

Intestinal Permeability in Relapsing-Remitting Multiple Sclerosis.

Author information

1
Centre for Experimental Neurological Therapies, Department of Neurosciences, Mental Health and Sensory Organs, Faculty of Medicine and Psychology, Sapienza University, via di Grottarossa, 1035, 00189, Rome, Italy.
2
Department of Neurology, University of Massachusetts Medical School, Worcester, MA, USA.
3
Department of Neurology and Psychiatry, Sapienza University, Rome, Italy.
4
Department of Informatics, Dana-Farber Cancer Institute, Boston, MA, USA.
5
IRCCS Istituto Neurologico Mediterraneo (INM) Neuromed, Pozzilli, Italy.
6
Centre for Experimental Neurological Therapies, Department of Neurosciences, Mental Health and Sensory Organs, Faculty of Medicine and Psychology, Sapienza University, via di Grottarossa, 1035, 00189, Rome, Italy. giovanni.ristori@uniroma1.it.

Abstract

Changes of intestinal permeability (IP) have been extensively investigated in inflammatory bowel diseases (IBD) and celiac disease (CD), underpinned by a known unbalance between microbiota, IP and immune responses in the gut. Recently the influence of IP on brain function has greatly been appreciated. Previous works showed an increased IP that preceded experimental autoimmune encephalomyelitis development and worsened during disease with disruption of TJ. Moreover, studying co-morbidity between Crohn's disease and MS, a report described increased IP in a minority of cases with MS. In a recent work we found that an alteration of IP is a relatively frequent event in relapsing-remitting MS, with a possible genetic influence on the determinants of IP changes (as inferable from data on twins); IP changes included a deficit of the active mechanism of absorption from intestinal lumen. The results led us to hypothesize that gut may contribute to the development of MS, as suggested by another previous work of our group: a population of CD8+CD161high T cells, belonging to the mucosal-associated invariant T (MAIT) cells, a gut- and liver-homing subset, proved to be of relevance for MS pathogenesis. We eventually suggest future lines of research on IP in MS: studies on IP changes in patients under first-line oral drugs may result useful to improve their therapeutic index; correlating IP and microbiota changes, or IP and blood-brain barrier changes may help clarify disease pathogenesis; exploiting the IP data to disclose co-morbidities in MS, especially with CD and IBD, may be important for patient care.

KEYWORDS:

Autoimmune comorbidity; Celiac disease; Crohn’ disease; Intestinal permeability; Mucosal-associated invariant T (MAIT) cells; Multiple sclerosis

PMID:
29119385
PMCID:
PMC5794695
[Available on 2019-01-01]
DOI:
10.1007/s13311-017-0582-3

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