Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Jun 23;12(7):1392.
doi: 10.3390/biomedicines12071392.

Multiple Sclerosis and Clostridium perfringens Epsilon Toxin: Is There a Relationship?

André Huss  1 , Franziska Bachhuber  1 , Cécile Feraudet-Tarisse  2 , Andreas Hiergeist  3 , Hayrettin Tumani  1
Affiliations

Multiple Sclerosis and Clostridium perfringens Epsilon Toxin: Is There a Relationship?

André Huss et al. Biomedicines. .

Abstract

Recent research has suggested a link between multiple sclerosis and the gut microbiota. This prospective pilot study aimed to investigate the composition of the gut microbiota in MS patients, the presence of Clostridium perfringens epsilon toxin in the serum of MS patients, and the influence of disease-modifying drugs (DMDs) on epsilon toxin levels and on the microbiota. Epsilon toxin levels in blood were investigated by two methods, a qualitative ELISA and a highly sensitive quantitative ELISA. Neither epsilon toxin nor antibodies against it were detected in the analyzed serum samples. 16S ribosomal RNA sequencing was applied to obtain insights into the composition of the gut microbiota of MS patients. No significant differences in the quantity, diversity, and the relative abundance of fecal microbiota were observed in the gut microbiota of MS patients receiving various DMDs, including teriflunomide, natalizumab, ocrelizumab, and fingolimod, or no therapy. The present study did not provide evidence supporting the hypothesis of a causal relationship between Clostridium perfringens epsilon toxin and multiple sclerosis.

Keywords: C. perfringens epsilon toxin; Clostridium perfringens; microbiota; multiple sclerosis.

PubMed Disclaimer

Conflict of interest statement

F.B. declares no conflicts of interest. The funders had no role in the design of this study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. A.H. declares no conflicts of interest. H.T. has participated in meetings sponsored by or received honoraria for acting as an advisor/speaker for Alexion, Bayer, Biogen, Bristol-Myers Squibb, Celgene, Diamed, Fresenius, Fujirebio, GlaxoSmithKline, Horizon, Janssen-Cilag, Merck, Novartis, Roche, Sanofi-Genzyme, Siemens, and Teva.

Figures

Figure 1
Figure 1
Total bacterial 16S rDNA copies. Group 1 (blue, no therapy); group 2 (red, teriflunomide); group 3 (green, other therapies).
Figure 2
Figure 2
Alpha diversity: V1V3 regions of 16S rDNA. Group 1 (blue, no therapy); group 2 (red, teriflunomide); group 3 (green, other therapies).
Figure 3
Figure 3
Beta diversity: Bray–Curtis distances. Group 1 (blue dots, no therapy); group 2 (red dots, teriflunomide); group 3 (green dots, other therapies). Large dots indicate the centroid of each group. Ellipses mark the 95 percent confidence intervals around each centroid.
Figure 4
Figure 4
Beta diversity principal coordinate analysis of bacterial bd (including phylogenetic distances): unweighted UNIFrac distance and weighted UNIFrac distance. Group 1 (blue dots, no therapy); group 2 (red dots, teriflunomide); group 3 (green dots, other therapies). Large dots indicate the centroid of each group. Ellipses mark the 95 percent confidence intervals around each centroid.
See this image and copyright information in PMC

References

    1. Berg G., Rybakova D., Fischer D., Cernava T., Vergès M.C., Charles T., Chen X., Cocolin L., Eversole K., Corral G.H., et al. Microbiome definition re-visited: Old concepts and new challenges. Microbiome. 2020;8:103. - PMC - PubMed
    1. Sharon G., Sampson T.R., Geschwind D.H., Mazmanian S.K. The Central Nervous System and the Gut Microbiome. Cell. 2016;167:915–932. doi: 10.1016/j.cell.2016.10.027. - DOI - PMC - PubMed
    1. Thirion F., Sellebjerg F., Fan Y., Lyu L., Hansen T.H., Pons N., Levenez F., Quinquis B., Stankevic E., Søndergaard H.B., et al. The gut microbiota in multiple sclerosis varies with disease activity. Genome Med. 2023;15:1. doi: 10.1186/S13073-022-01148-1. - DOI - PMC - PubMed
    1. Berer K., Mues M., Koutrolos M., Al Rasbi Z., Boziki M., Johner C., Wekerle H., Krishnamoorthy G. Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination. Nature. 2011;479:538. doi: 10.1038/nature10554. - DOI - PubMed
    1. Berer K., Gerdes L.A., Cekanaviciute E., Jia X., Xiao L., Xia Z., Liu C., Klotz L., Stauffer U., Baranzini S.E., et al. Gut microbiota from multiple sclerosis patients enables spontaneous autoimmune encephalomyelitis in mice. Proc. Natl. Acad. Sci. USA. 2017;114:10719–10724. doi: 10.1073/pnas.1711233114. - DOI - PMC - PubMed

LinkOut - more resources