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.
Department of Neurology, University of Massachusetts Medical School, Worcester, MA, USA.
Neurotherapeutics. 2018 Jan;15(1):68-74. doi: 10.1007/s13311-017-0582-3.
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.
肠通透性 (IP) 的变化在炎症性肠病 (IBD) 和乳糜泻 (CD) 中得到了广泛研究，这是基于肠道中微生物群、IP 和免疫反应之间已知的失衡。最近，人们对 IP 对大脑功能的影响有了更多的认识。以前的研究表明，在实验性自身免疫性脑脊髓炎发展之前，IP 增加，并在疾病期间随着 TJ 的破坏而恶化。此外，在研究克罗恩病和多发性硬化症的共病时，有一份报告描述了少数多发性硬化症病例中 IP 的增加。在最近的一项研究中，我们发现 IP 的改变在复发性缓解型多发性硬化症中是一个相对常见的事件，其变化的决定因素可能存在遗传影响（可从关于双胞胎的数据中推断出来）；IP 的改变包括从肠腔主动吸收机制的缺陷。这些结果使我们假设肠道可能有助于多发性硬化症的发展，正如我们小组的另一项先前研究所示：一群 CD8+CD161high T 细胞，属于黏膜相关不变 T (MAIT) 细胞，一种肠道和肝脏归巢的亚群，被证明与多发性硬化症的发病机制有关。我们最终建议对多发性硬化症中的 IP 进行未来的研究：对一线口服药物治疗的患者的 IP 变化进行研究可能有助于提高其治疗指数；将 IP 与微生物群变化或 IP 与血脑屏障变化相关联可能有助于阐明疾病发病机制；利用 IP 数据揭示多发性硬化症的共病，特别是与乳糜泻和 IBD 的共病，对患者护理可能很重要。
