The Contribution of Gut Barrier Changes to Multiple Sclerosis Pathophysiology.

Maria Chiara Buscarinu,Michela Ferraldeschi,Roberta Reniè,Marco Salvetti,Giovanni Ristori,Silvia Romano,Anna Chiara Landi,Arianna Fornasiero,Emanuele Morena,Rosella Mechelli,Giulia Pellicciari,Carmela Romano

doi:10.3389/fimmu.2019.01916

Abstract

The gut barrier consists of several components, including the mucus layer, made of mucins and anti-bacterial molecule, the epithelial cells, connected by tight junction proteins, and a mixed population of cells involved in the interplay with microbes, such as M cells, elongations of “antigen presenting cells” dwelling the lamina propria, intraepithelial lymphocytes and Paneth cells secreting anti-bacterial peptides. Recently, the influence of intestinal permeability (IP) changes on organs far from gut has been investigated, and IP changes in multiple sclerosis (MS) have been described. A related topic is the microbiota dysfunction that underpins the development of neuroinflammation in animal models and human diseases, including MS. It becomes now of interest to better understand the mechanisms through which IP changes contribute to pathophysiology of neuroinflammation. The following aspects seem of relevance: studies on other biomarkers of IP alterations; the relationship with known risk factors for MS development, such as vitamin D deficiency; the link between blood brain barrier and gut barrier breakdown; the effects of IP increase on microbial translocation and microglial activation; the parallel patterns of IP and neuroimmune changes in MS and neuropsychiatric disorders, that afflict a sizable proportion of patients with MS. We will also discuss the therapeutic implications of IP changes, considering the impact of MS-modifying therapies on gut barrier, as well as potential approaches to enhance or protect IP homeostasis.

Highlights

The Contribution of Gut Barrier Changes to Multiple Sclerosis PathophysiologyMaria Chiara Buscarinu 1, Arianna Fornasiero 1, Silvia Romano 1, Michela Ferraldeschi 2, Rosella Mechelli 3, Roberta Reniè 1, Emanuele Morena 1, Carmela Romano 1, Giulia Pellicciari 1, Anna Chiara Landi 1, Marco Salvetti 1,4* and Giovanni Ristori 1*
The requirement for different functions is reflected by the structural complexity of the intestinal surface
We reported that an alteration of intestinal permeability (IP) is a relatively frequent event in multiple sclerosis (MS)

Summary

The Contribution of Gut Barrier Changes to Multiple Sclerosis Pathophysiology

Maria Chiara Buscarinu 1, Arianna Fornasiero 1, Silvia Romano 1, Michela Ferraldeschi 2, Rosella Mechelli 3, Roberta Reniè 1, Emanuele Morena 1, Carmela Romano 1, Giulia Pellicciari 1, Anna Chiara Landi 1, Marco Salvetti 1,4* and Giovanni Ristori 1*. A related topic is the microbiota dysfunction that underpins the development of neuroinflammation in animal models and human diseases, including MS. It becomes of interest to better understand the mechanisms through which IP changes contribute to pathophysiology of neuroinflammation. The following aspects seem of relevance: studies on other biomarkers of IP alterations; the relationship with known risk factors for MS development, such as vitamin D deficiency; the link between blood brain barrier and gut barrier breakdown; the effects of IP increase on microbial translocation and microglial activation; the parallel patterns of IP and neuroimmune changes in MS and neuropsychiatric disorders, that afflict a sizable proportion of patients with MS. We will discuss the therapeutic implications of IP changes, considering the impact of MS-modifying therapies on gut barrier, as well as potential approaches to enhance or protect IP homeostasis

INTRODUCTION

Intestinal Permeability Changes and MS Pathophysiology

Microbiota transplantation

Translational Implications