Intestinal Permeability in Relapsing-Remitting Multiple Sclerosis

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.

The role of the retinoids in schizophrenia: genomic and clinical perspectives

“…Retinoids further act as regulators of the blood-gut barrier-a vital structure for preventing inflammation in response to the gut microbiome [68]. Aberrant permeability ('leakiness') in this barrier has been linked with several inflammatory conditions and may also have implications for adverse immune responses associated with schizophrenia [69,70]. A more direct link between retinoids and neuroinflammation is mediated by the action of at-RA on astrocyte and microglial populations, whereby at-RA downregulates their activity [71].…”

The Microbiome and Neurologic Disease: Past and Future of a 2-Way Interaction

“…Furthermore, SCI induced increases in the intestinal barrier permeability. As discussed by Marietta et al [2], and more specifically by Buscarini et al [6] in the context of multiple sclerosis (MS), disruption of intestinal permeability is associated with neurologic diseases. Bacterial translocation, defined as the movement of bacteria or bacterial products across the intestinal epithelium, also characterizes SCI effects on the intestinal environment, as gut microbes were isolated from mesenteric lymph nodes.…”

“…The induction of EAE in mice has remarkable cellular and molecular effects on the intestinal barrier by promoting the induction of a Bleaky gut^and accumulation of proinflammatory Th17 and Th1 cells, concomitant with reductions in regulatory T cells in the intestinal mucosa [25]. The effects of MS in intestinal barrier disruption are reviewed by Buscarini et al [6]. These authors discuss the relatively high frequency of intestinal barrier dysfunction in patients with MS, perhaps inherited genetically.…”

Focus on the gut-brain axis: Multiple sclerosis, the intestinal barrier and the microbiome

“…It has been hypothesized that an altered intestinal barrier might lead to bacterial translocation thus allowing the passage of noxious molecules such as microbial associated molecular patterns. This could then alter peripheral immune responses or allow these molecules to enter the CNS and alter neuroimmunity[ 26 , 43 ].…”