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The Gut-Brain Axis in Multiple Sclerosis. Is Its Dysfunction a Pathological Trigger or a Consequence of the Disease?
Frontiers in Immunology ( IF 7.3 ) Pub Date : 2021-09-21 , DOI: 10.3389/fimmu.2021.718220
Benedetta Parodi 1 , Nicole Kerlero de Rosbo 1, 2
Affiliation  

A large and expending body of evidence indicates that the gut-brain axis likely plays a crucial role in neurological diseases, including multiple sclerosis (MS). As a whole, the gut-brain axis can be considered as a bi-directional multi-crosstalk pathway that governs the interaction between the gut microbiota and the organism. Perturbation in the commensal microbial population, referred to as dysbiosis, is frequently associated with an increased intestinal permeability, or “leaky gut”, which allows the entrance of exogeneous molecules, in particular bacterial products and metabolites, that can disrupt tissue homeostasis and induce inflammation, promoting both local and systemic immune responses. An altered gut microbiota could therefore have significant repercussions not only on immune responses in the gut but also in distal effector immune sites such as the CNS. Indeed, the dysregulation of this bi-directional communication as a consequence of dysbiosis has been implicated as playing a possible role in the pathogenesis of neurological diseases. In multiple sclerosis (MS), the gut-brain axis is increasingly being considered as playing a crucial role in its pathogenesis, with a major focus on specific gut microbiota alterations associated with the disease. In both MS and its purported murine model, experimental autoimmune encephalomyelitis (EAE), gastrointestinal symptoms and/or an altered gut microbiota have been reported together with increased intestinal permeability. In both EAE and MS, specific components of the microbiota have been shown to modulate both effector and regulatory T-cell responses and therefore disease progression, and EAE experiments with germ-free and specific pathogen-free mice transferred with microbiota associated or not with disease have clearly demonstrated the possible role of the microbiota in disease pathogenesis and/or progression. Here, we review the evidence that can point to two possible consequences of the gut-brain axis dysfunction in MS and EAE: 1. A pro-inflammatory intestinal environment and “leaky” gut induced by dysbiosis could lead to an altered communication with the CNS through the cholinergic afferent fibers, thereby contributing to CNS inflammation and disease pathogenesis; and 2. Neuroinflammation affecting efferent cholinergic transmission could result in intestinal inflammation as disease progresses.



中文翻译:

多发性硬化症中的肠脑轴。它的功能障碍是病理触发还是疾病的后果?

大量且不断扩展的证据表明,肠-脑轴可能在神经系统疾病中起着至关重要的作用,包括多发性硬化症 (MS)。总的来说,肠-脑轴可以被认为是一个双向的多串扰通路,它控制着肠道微生物群和生物体之间的相互作用。共生微生物群的扰动,称为生态失调,通常与肠道通透性增加或“肠漏”有关,这会导致外源性分子(尤其是细菌产物和代谢物)进入,从而破坏组织稳态并诱发炎症,促进局部和全身免疫反应。因此,改变的肠道微生物群不仅会对肠道的免疫反应产生显着影响,还会对远端效应免疫位点(如中枢神经系统)产生重大影响。事实上,作为生态失调的结果,这种双向交流的失调被认为在神经系统疾病的发病机制中发挥着可能的作用。在多发性硬化症 (MS) 中,肠脑轴越来越被认为在其发病机制中起着至关重要的作用,主要关注与该疾病相关的特定肠道微生物群的改变。在 MS 及其声称的小鼠模型中,已经报道了实验性自身免疫性脑脊髓炎 (EAE)、胃肠道症状和/或肠道微生物群改变以及肠道通透性增加。在 EAE 和 MS 中,微生物群的特定成分已被证明可以调节效应和调节性 T 细胞反应,从而调节疾病进展,并且在无菌和无特定病原体小鼠身上进行的 EAE 实验清楚地证明了可能的作用微生物群在疾病发病机制和/或进展中的作用。在这里,我们回顾了可以指出 MS 和 EAE 中肠-脑轴功能障碍的两种可能后果的证据:1. 由生态失调引起的促炎肠道环境和“泄漏”肠道可能导致与中枢神经系统的交流改变通过胆碱能传入纤维,从而促进中枢神经系统炎症和疾病发病机制;和 2。

更新日期:2021-09-21
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