Department of Immunology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan; Multiple Sclerosis Center, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan; Laboratory for Symbiotic Microbiome Sciences, RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
Laboratory for Symbiotic Microbiome Sciences, RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan; Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Chiba 277-8568, Japan.
Cell Rep. 2024 Oct 22;43(10):114785. doi: 10.1016/j.celrep.2024.114785. Epub 2024 Sep 27.
Multiple sclerosis (MS) is an autoimmune-demyelinating disease with an inflammatory pathology formed by self-reactive lymphocytes with activated glial cells. Progressive MS, characterized by resistance to medications, significantly differs from the non-progressive form in gut microbiome profiles. After confirming an increased abundance of "Tyzzerella nexilis" in various cohorts of progressive MS, we identified a distinct cluster of T. nexilis strains enriched in progressive MS based on long-read metagenomics. The distinct T. nexilis cluster is characterized by a large number of mobile genetic elements (MGEs) and a lack of defense systems against MGEs. Microbial genes for sulfate reduction and flagella formation with pathogenic implications are specific to this cluster. Moreover, these flagellar genes are encoded on MGEs. Mono-colonization with MGE-enriched T. nexilis made germ-free mice more susceptible to experimental autoimmune encephalomyelitis. These results indicate that the progression of MS may be promoted by MGE-enriched T. nexilis with potentially pathogenic properties.
多发性硬化症（MS）是一种自身免疫性脱髓鞘疾病，其炎症病理学由自身反应性淋巴细胞和激活的神经胶质细胞形成。进展性 MS 与非进展性 MS 在肠道微生物组特征上有显著差异，其特征是对药物有抗性。在确认“Tyzzerella nexilis”在各种进展性 MS 队列中的丰度增加后，我们基于长读宏基因组学鉴定了一个在进展性 MS 中富集的独特 T. nexilis 菌株簇。这个独特的 T. nexilis 菌株簇的特点是大量的移动遗传元件（MGEs）和缺乏针对 MGEs 的防御系统。具有致病性的硫酸盐还原和鞭毛形成的微生物基因是这个菌株簇所特有的。此外，这些鞭毛基因编码在 MGEs 上。用富含 MGE 的 T. nexilis 进行单定植使无菌小鼠更容易发生实验性自身免疫性脑脊髓炎。这些结果表明，MS 的进展可能是由具有潜在致病性的富含 MGE 的 T. nexilis 所促进的。
