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.

中文翻译：

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用富马酸二甲酯治疗复发缓解型多发性硬化症患者的肠道通透性和循环 CD161+CCR6+CD8+T 细胞。

背景：肠-脑轴的变化最近被认为是多发性硬化症 (MS) 发病机制的重要组成部分。目的：评价DMF对肠道屏障通透性和粘膜免疫反应的影响。方法：我们调查了 25 名符合富马酸二甲酯 (DMF) 治疗资格标准的 MS 患者的肠道通透性 (IP) 和循环 CD161+CCR6+CD8+T 细胞。这些数据以及临床/MRI 参数在三个时间点进行了研究：基线（治疗前）、治疗后 1 个月（T1）和 9 个月（T2）。结果：在基线时，16 名患者 (64%) 显示 IP 改变，而 14 例 (56%) 显示活动性 MRI。在 DMF 治疗期间，我们发现与 T0 相比，MRI 的疾病活动性预期降低（T1 时为 6/25，p = 0.035，T2 时为 3/25，p < 0.00），CD161+CCR6+CD8+T 细胞百分比降低（T2 时为 16/23；p < 0.001）。DMF 对肠道屏障改变的影响是可变的，没有明确的纵向模式，而我们发现 IP 变化与 MRI 活性下降（p = 0.04）和循环 CD161+CCr6+CD8+ T 细胞（p = 0.023）之间存在显着关系。结论：MS 中肠道屏障经常发生改变，CD161+ CCR6+CD8+ T 细胞亚群显示出与病程和治疗相关的动态。