Erysipelotrichaceae bacterium OTU0002 isolated from mouse small intestine. Erysipelotrichaceae bacterium OTU0002

Accumulating evidence indicates that gut microbes play a pathogenic role in autoimmune diseases including multiple sclerosis (MS). Here, we show that two distinct signals from gut microbes coordinately activate myelin oligodendrocyte glycoprotein (MOG)-specific autoreactive T cells in the small intestine (SI). After induction of experimental autoimmune encephalomyelitis (EAE), an animal model for MS, MOG-specific CD4 T cells can be observed in the SI. Germ-free (GF) mice monocolonized with SI microbes demonstrated that a newly isolated Erysipelotrichaceae strain adheres to SI epithelial cells and enhances Th17 responses, via inducing serum amyloid A and IL-23, that were associated with an increased susceptibility to EAE. Shotgun sequencing of SI contents revealed that a Lactobacillus strain possesses potential mimicry peptides to MOG. While monocolonization of GF mice with the Lactobacillus strain did not enhance EAE development or severity, co-colonized mice with Erysipelotrichaceae and Lactobacillus strains resulted in more severe EAE.

越来越多的研究证据表明，肠道微生物在多发性硬化症（multiple sclerosis, MS）等自身免疫性疾病中发挥致病作用。本研究证实，肠道菌群来源的两种不同信号可协同激活小肠（small intestine, SI）内针对髓鞘少突胶质细胞糖蛋白（myelin oligodendrocyte glycoprotein, MOG）的自身反应性T细胞。在诱导作为多发性硬化症动物模型的实验性自身免疫性脑脊髓炎（experimental autoimmune encephalomyelitis, EAE）后，可在小肠中检测到MOG特异性CD4阳性T细胞。对单定植小肠微生物的无菌（germ-free, GF）小鼠开展的研究显示，一株新分离的丹毒丝菌科（Erysipelotrichaceae）菌株可黏附于小肠上皮细胞，并通过诱导血清淀粉样蛋白A与白细胞介素23的表达增强Th17细胞应答，该效应与EAE易感性升高相关。对小肠内容物进行鸟枪测序的结果显示，一株乳杆菌属（Lactobacillus）菌株携带与MOG具有潜在模拟活性的肽段。尽管单独使用该乳杆菌菌株定植无菌小鼠并不会增强EAE的发生概率或病情严重程度，但同时定植丹毒丝菌科菌株与乳杆菌菌株的小鼠可出现更为严重的EAE症状。