A team at Weill Cornell Medical College and collaborators have
published a report suggesting that people with MS have an increased presence and abundance of a toxin-producing bacterium in their intestines. The team also showed in lab mice that this bacterium - Clostridium perfringens – could facilitate the entry of damaging immune cells and molecules into the brain and spinal cord and produce tissue damage and symptoms similar to what is seen in people with MS.
The researchers suggest that the bacterium and the toxin it produces, called Epsilon Toxin, may work with
other factors that may increase susceptibility, such as Epstein-Barr virus, to trigger MS.
DETAILS
Background: In recent years evidence has been growing around the influence of the bacteria and other microbes that reside in the intestines (“gut microbiome”) and MS disease activity. Most of these are harmless and some appear to play a critical role in our normal physiology, such as in establishing and maintaining immune balance by the molecules they release.
A team led by Dr. Timothy Vartanian has been pursuing a possible link between Epsilon Toxin, produced by some strains of the bacterium Clostridium perfringens in the gut, and MS. Some strains of this bacterium can cause food poisoning.
Study: The team recruited 62 participants with and without MS who were matched by age, location, body mass and other characteristics. All provided stool samples The researchers used advanced lab techniques to amplify the signals of the microbes in the stool samples and compared differences in bacterial content of people with MS and people without MS. The study was supported by the National MS Society, National Institutes of Health and others.
- They found that people with MS had gut Clostridium perfringens much more frequently, and with greater abundance, than people without MS.
- The team was able to trigger an MS-like disease (EAE) in lab mice by introducing Epsilon Toxin along with a protein of myelin. This occurred because the toxin could facilitate the breakdown the barrier that normally protects the brain and spinal cord from foreign substances in the blood.
- They found that the MS-like disease in mice induced by Epsilon Toxin more closely resembled MS damage to the brain and spinal cord and symptoms than the usual form of mouse EAE.
Next Steps: The researchers suggest that Epsilon Toxin may act as a triggering factor for MS. Further study is needed to confirm this and to determine whether finding ways to eliminate strains of Clostridium perfringens that produce Epsilon Toxin could treat MS. Ongoing research by the International MS Microbiome Study Consortium and others should continue to increase our understanding about how specific species in the gut may protect against or contribute to MS disease activity.
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Epsilon toxin-producing Clostridium perfringens colonize the MS gut and epsilon toxin overcomes immune privilege,” by Yinghua Ma, David Sannino, Jennifer R. Linden, Sylvia Haigh, Baohua Zhao, John B. Grigg, Paul Zumbo, Friederike Dündar, Daniel J. Butler, Caterina P. Profaci, Kiel M. 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 W. Kaunzner, Ilana L. Brito, Zhengming Chen, Jenny Z. Xiang, Doron Betel, Richard Daneman, Gregory F. Sonnenberg, Christopher E. Mason, and Timothy Vartanian, was
published online on February 28, 2023 in the
Journal of Clinical Investigation.