Gut microorganisms act together to exacerbate inflammation in spinal cords
Gut microorganisms act together to exacerbate inflammation in spinal cords
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DOI：
10.1038/s41586-020-2634-9
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发表时间：
2020-08-26
期刊：
影响因子：
64.8
通讯作者：
Ohno, Hiroshi
中科院分区：
文献类型：
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作者：
Miyauchi, Eiji;Kim, Seok-Won;Ohno, Hiroshi
与来自小肠菌群的两种菌株共定殖的无菌小鼠对实验性自身免疫性脑脊髓炎的易感性增加，暗示这些微生物在多发性硬化症小鼠模型中的协同作用。越来越多的证据表明，肠道微生物在自身免疫性疾病中起致病作用，包括多发性硬化症(1)。实验性自身免疫性脑脊髓炎（多发性硬化症的动物模型）的研究（2,3）以及人体研究（4-6）表明，肠道微生物与多发性硬化症的发展或严重程度有关。然而，目前尚不清楚肠道微生物如何作用于肠道外组织（如脊髓）的炎症。在这里，我们发现来自肠道微生物的两种不同信号协同激活小肠中的自身反应性T细胞，这些T细胞对髓鞘少突胶质细胞糖蛋白（MOG）做出特异性反应。小鼠诱导实验性自身免疫性脑脊髓炎后，在小肠中观察到mog特异性CD4(+)T细胞。用无菌小鼠单定殖小肠微生物的实验表明，一种新分离的丹毒科菌株类似于佐剂，可以增强T辅助17细胞的应答。对小肠内容物的鸟枪测序显示，一株罗伊氏乳杆菌具有可能模拟MOG的肽。与这两种菌株共定植的小鼠表现出比无菌或单定植的小鼠更严重的实验性自身免疫性脑脊髓炎症状。这些数据表明，在多发性硬化症的致病性中应考虑到这些微生物的存在所产生的协同效应，对这些微生物的进一步研究可能会导致这种疾病的预防策略。
Germ-free mice co-colonized with two bacterial strains from the small intestinal flora showed increased susceptibility to experimental autoimmune encephalomyelitis, implicating the synergistic effects of these microorganisms in this mouse model of multiple sclerosis.Accumulating evidence indicates that gut microorganisms have a pathogenic role in autoimmune diseases, including in multiple sclerosis(1). Studies of experimental autoimmune encephalomyelitis (an animal model of multiple sclerosis)(2,3), as well as human studies(4-6), have implicated gut microorganisms in the development or severity of multiple sclerosis. However, it remains unclear how gut microorganisms act on the inflammation of extra-intestinal tissues such as the spinal cord. Here we show that two distinct signals from gut microorganisms coordinately activate autoreactive T cells in the small intestine that respond specifically to myelin oligodendrocyte glycoprotein (MOG). After induction of experimental autoimmune encephalomyelitis in mice, MOG-specific CD4(+)T cells are observed in the small intestine. Experiments using germ-free mice that were monocolonized with microorganisms from the small intestine demonstrated that a newly isolated strain in the family Erysipelotrichaceae acts similarly to an adjuvant to enhance the responses of T helper 17 cells. Shotgun sequencing of the contents of the small intestine revealed a strain ofLactobacillus reuterithat possesses peptides that potentially mimic MOG. Mice that were co-colonized with these two strains showed experimental autoimmune encephalomyelitis symptoms that were more severe than those of germ-free or monocolonized mice. These data suggest that the synergistic effects that result from the presence of these microorganisms should be considered in the pathogenicity of multiple sclerosis, and that further study of these microorganisms may lead to preventive strategies for this disease.