2. Academic Validation
  3. Tyzzerella nexilis strains enriched in mobile genetic elements are involved in progressive multiple sclerosis

Tyzzerella nexilis strains enriched in mobile genetic elements are involved in progressive multiple sclerosis

  • Cell Rep. 2024 Oct 22;43(10):114785. doi: 10.1016/j.celrep.2024.114785.
Daiki Takewaki 1,  Yuya Kiguchi 2,  Hiroaki Masuoka 3,  Mallahalli S Manu 4,  Ben J E Raveney 1,  Seiko Narushima 5,  Rina Kurokawa 3,  Yusuke Ogata 3,  Yukio Kimura 6,  Noriko Sato 6,  Yusuke Ozawa 7,  Sosuke Yagishita 7,  Toshiyuki Araki 7,  Sachiko Miyake 8,  Wakiro Sato 4,  Wataru Suda 9,  Takashi Yamamura 10
Affiliations

Affiliations

  • 1 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.
  • 2 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.
  • 3 Laboratory for Symbiotic Microbiome Sciences, RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
  • 4 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.
  • 5 Laboratory for Mucosal Immunity, RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
  • 6 Multiple Sclerosis Center, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan; Department of Radiology, National Center of Neurology and Psychiatry Hospital, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan.
  • 7 Department of Peripheral Nervous System Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan.
  • 8 Department of Immunology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
  • 9 Laboratory for Symbiotic Microbiome Sciences, RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan. Electronic address: wataru.suda@riken.jp.
  • 10 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. Electronic address: yamamura@ncnp.go.jp.
PMID: 39341204 DOI: 10.1016/j.celrep.2024.114785
Abstract

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.

Keywords

CP: Microbiology; Tyzzerella nexilis; experimental autoimmune encephalomyelitis; flagella; gut microbiome; long-read metagenomics; mobile genetic elements; multiple sclerosis; sulfate reduction.

Figures
Products