Tyzzerella nexilis strains enriched in mobile genetic elements are involved in progressive multiple sclerosis
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.
Authors
- Yusuke Ozawa (ORCID: https://orcid.org/0000-0002-4660-6193)
- Yuya Kiguchi (ORCID: https://orcid.org/0000-0003-3334-2018)
- Rina Kurokawa (ORCID: https://orcid.org/0000-0002-2238-2826)
- Sachiko Miyake (ORCID: https://orcid.org/0000-0001-6349-2936)
- Hiroaki Masuoka (ORCID: https://orcid.org/0000-0001-5442-7104)
- Daiki Takewaki (ORCID: https://orcid.org/0000-0002-9232-4031)
- Takashi Yamamura (ORCID: https://orcid.org/0000-0001-9048-0375)
- Seiko Narushima (ORCID: https://orcid.org/0000-0002-3001-2446)
- Wataru Suda (ORCID: https://orcid.org/0000-0002-2861-9724)
- Wakiro Sato (ORCID: https://orcid.org/0000-0003-4082-3557)
- Sosuke Yagishita (ORCID: https://orcid.org/0000-0002-3396-1313)
- Yukio Kimura (ORCID: https://orcid.org/0000-0002-7979-0863)
- Ben J. E. Raveney (ORCID: https://orcid.org/0000-0003-2641-5733)
- Toshiyuki Araki (ORCID: https://orcid.org/0000-0003-3625-2042)
- Yusuke Ogata (ORCID: https://orcid.org/0000-0002-5993-4356)
- Noriko Sato (ORCID: https://orcid.org/0000-0002-9305-7131)
- Mallahalli S. Manu
Institutions
- Juntendo University (JP)
- National Center of Neurology and Psychiatry (JP)
- RIKEN Center for Integrative Medical Sciences (JP)
Publication Details
- Journal
- Cell Reports
- Published
- 2024-09-27
- DOI
- https://doi.org/10.1016/j.celrep.2024.114785
- Citations
- 4
- Primary Topic
- Mycobacterium research and diagnosis
- Type
- article
- Field-Weighted Citation Impact
- 1.55
Funders
- Japan Agency for Medical Research and Development