Melamed Esther, Palmer Jamie L, Fonken Cara
Department of Neurology, Dell Medical School, University of Texas at Austin, Austin, TX, United States.
Front Mol Neurosci. 2022 Nov 4;15:1019877. doi: 10.3389/fnmol.2022.1019877. eCollection 2022.
Since the first model of experimental autoimmune encephalomyelitis (EAE) was introduced almost a century ago, there has been an ongoing scientific debate about the risks and benefits of using EAE as a model of multiple sclerosis (MS). While there are notable limitations of translating EAE studies directly to human patients, EAE continues to be the most widely used model of MS, and EAE studies have contributed to multiple key breakthroughs in our understanding of MS pathogenesis and discovery of MS therapeutics. In addition, insights from EAE have led to a better understanding of modifiable environmental factors that can influence MS initiation and progression. In this review, we discuss how MS patient and EAE studies compare in our learning about the role of gut microbiome, diet, alcohol, probiotics, antibiotics, and fecal microbiome transplant in neuroinflammation. Ultimately, the combination of rigorous EAE animal studies, novel bioinformatic approaches, use of human cell lines, and implementation of well-powered, age- and sex-matched randomized controlled MS patient trials will be essential for improving MS patient outcomes and developing novel MS therapeutics to prevent and revert MS disease progression.
自近一个世纪前引入首个实验性自身免疫性脑脊髓炎（EAE）模型以来，关于将EAE用作多发性硬化症（MS）模型的风险和益处的科学争论一直在持续。虽然将EAE研究直接转化为人类患者存在显著局限性，但EAE仍然是MS最广泛使用的模型，并且EAE研究为我们对MS发病机制的理解和MS治疗方法的发现做出了多项关键突破。此外，来自EAE的见解使人们对可影响MS发病和进展的可改变环境因素有了更好的理解。在这篇综述中，我们讨论了在了解肠道微生物群、饮食、酒精、益生菌、抗生素和粪便微生物群移植在神经炎症中的作用方面，MS患者研究与EAE研究如何进行比较。最终，严格的EAE动物研究、新颖的生物信息学方法、人类细胞系的使用以及有足够效力、年龄和性别匹配的随机对照MS患者试验的实施，对于改善MS患者的预后以及开发预防和逆转MS疾病进展的新型MS治疗方法至关重要。
