作者
Yinghua Ma, David Sannino, Jennifer R Linden, Sylvia Haigh, Baohua Zhao, John B Grigg, Paul Zumbo, Friederike Dündar, Daniel Butler, Caterina P Profaci, Kiel Telesford, Paige N Winokur, Kareem R Rumah, Susan A Gauthier, Vincent A Fischetti, Bruce A McClane, Francisco A Uzal, Lily Zexter, Michael Mazzucco, Richard Rudick, David Danko, Evan Balmuth, Nancy Nealon, Jai Perumal, Ulrike Kaunzner, Ilana L Brito, Zhengming Chen, Jenny Z Xiang, Doron Betel, Richard Daneman, Gregory F Sonnenberg, Christopher E Mason, Timothy Vartanian
发表日期
2023/5/1
期刊
The Journal of clinical investigation
卷号
133
期号
9
出版商
American Society for Clinical Investigation
简介
Multiple sclerosis (MS) is a complex disease of the CNS thought to require an environmental trigger. Gut dysbiosis is common in MS, but specific causative species are unknown. To address this knowledge gap, we used sensitive and quantitative PCR detection to show that people with MS were more likely to harbor and show a greater abundance of epsilon toxin–producing (ETX-producing) strains of C. perfringens within their gut microbiomes compared with individuals who are healthy controls (HCs). Isolates derived from patients with MS produced functional ETX and had a genetic architecture typical of highly conjugative plasmids. In the active immunization model of experimental autoimmune encephalomyelitis (EAE), where pertussis toxin (PTX) is used to overcome CNS immune privilege, ETX can substitute for PTX. In contrast to PTX-induced EAE, where inflammatory demyelination is largely restricted to the …
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Y Ma, D Sannino, JR Linden, S Haigh, B Zhao… - The Journal of clinical investigation, 2023