ArticleThe Journal of clinical investigation2023
Epsilon toxin-producing Clostridium perfringens colonize the multiple sclerosis gut microbiome overcoming CNS immune privilege.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
30 citing papers in PubMed, 46 citations in OpenAlex.
- Antigen-specific activation of gut immune cells drives autoimmune neuroinflammation.Gut microbes · 2026Article
- The Gut Microbiome in Multiple Sclerosis.Neurology(R) neuroimmunology & neuroinflammation · 2026Review
- Infection control in the brain and the eye.Acta ophthalmologica · 2026Review
- Article
- Microbial-Immune Interplay in CNS Autoimmune Diseases: Lessons from Animal Models and Clinical Studies.European journal of immunology · 2026Review
- Milestones in Clostridium perfringens research since 1995.Anaerobe · 2025Review
- Potential mechanisms linking bacterial factors to the development and progression of multiple sclerosis.Infectious medicine · 2025Review
- Review
- Phage-Microbiota Crosstalk: Implications for Central Nervous System Disorders.International journal of molecular sciences · 2025Review
- Bifidobacterium deficit in United States infants drives prevalent gut dysbiosis.Communications biology · 2025Article
- Prevalence of epsilon toxin-producing Clostridium perfringens isolates among patients with multiple sclerosis and neuromyelitis optica spectrum disorder in Iran.BMC neurology · 2025Article
- Specific microbial ratio in the gut microbiome is associated with multiple sclerosis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Alterations in Gut Microbiome-Host Relationships After Immune Perturbation in Patients With Multiple Sclerosis.Neurology(R) neuroimmunology & neuroinflammation · 2025Article
- Gut microbiota in multiple sclerosis and animal models.The FEBS journal · 2025Review
- Inflammatory disease microbiomes share a functional pathogenicity predicted by C-reactive protein.bioRxiv : the preprint server for biology · 2025Article
- Lupus and inflammatory bowel disease share a common set of microbiome features distinct from other autoimmune disorders.Annals of the rheumatic diseases · 2025Observational
- Epsilon Toxin fromToxins · 2024Article
- The epsilon toxin from Clostridium perfringens stimulates calcium-activated chloride channels, generating extracellular vesicles in Xenopus oocytes.Pharmacology research & perspectives · 2024Article
- Review
- The Molecular Architecture and Mode of Action ofToxins · 2024Review
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Authors and funding
33 authors at 7 institutions in 2 countries.
Funding
Abstract
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 spinal cord, ETX-induced EAE caused demyelination in the corpus callosum, thalamus, cerebellum, brainstem, and spinal cord, more akin to the neuroanatomical lesion distribution seen in MS. CNS endothelial cell transcriptional profiles revealed ETX-induced genes that are known to play a role in overcoming CNS immune privilege. Together, these findings suggest that ETX-producing C. perfringens strains are biologically plausible pathogens in MS that trigger inflammatory demyelination in the context of circulating myelin autoreactive lymphocytes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.