Abstract
Background: The changes of the gut-brain axis have been recently recognized as important components in multiple sclerosis (MS) pathogenesis.Objectives: To evaluate the effects of DMF on intestinal barrier permeability and mucosal immune responses.Methods: We investigated intestinal permeability (IP) and circulating CD161+CCR6+CD8+T cells in 25 patients with MS, who met eligibility criteria for dimethyl-fumarate (DMF) treatment. These data, together with clinical/MRI parameters, were studied at three time-points: baseline (before therapy), after one (T1) and 9 months (T2) of treatment.Results: At baseline 16 patients (64%) showed altered IP, while 14 cases (56%) showed active MRI. During DMF therapy we found the expected decrease of disease activity at MRI compared to T0 (6/25 at T1, p = 0.035 and 3/25 at T2, p < 0.00), and a reduction in the percentage of CD161+CCR6+CD8+ T cells (16/23 at T2; p < 0.001). The effects of DMF on gut barrier alterations was variable, without a clear longitudinal pattern, while we found significant relationships between IP changes and drop of MRI activity (p = 0.04) and circulating CD161+CCr6+CD8+ T cells (p = 0.023).Conclusions: The gut barrier is frequently altered in MS, and the CD161+ CCR6+CD8+ T cell-subset shows dynamics which correlate with disease course and therapy.
Highlights
Multiple sclerosis (MS) is a chronic disease of the central nervous system (CNS), with inflammation, demyelination, and neurodegeneration
During DMF therapy we found the expected decrease of disease activity at magnetic resonance imaging (MRI) compared to T0 (6/25 at T1, p = 0.035 and 3/25 at T2, p < 0.00), and a reduction in the percentage of CD161+CCR6+CD8+ T cells (16/23 at T2; p < 0.001)
The effects of DMF on gut barrier alterations was variable, without a clear longitudinal pattern, while we found significant relationships between intestinal permeability (IP) changes and drop of MRI activity (p = 0.04) and circulating CD161+CCr6+CD8+ T cells (p = 0.023)
Summary
Multiple sclerosis (MS) is a chronic disease of the central nervous system (CNS), with inflammation, demyelination, and neurodegeneration. Microbiota and gut function are increasingly recognized as relevant in this immune-mediated disorder [2]. Several studies have recently shown that the microbiota, as a part of the intestine–brain axis, plays a role in the etiopathogenesis of MS [3, 4]. A crucial component of this axis, the intestinal barrier, has received much less attention. The question of whether or not intestinal permeability (IP) is affected during the disease course is at least as important as the changes in the microbiota balance [5, 6]. The changes of the gut-brain axis have been recently recognized as important components in multiple sclerosis (MS) pathogenesis
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