Toxin from common foodborne bacteria discovered as potential MS trigger
Researchers at Weill Cornell Medical College in New York presented new findings on the link between a toxin produced by common foodborne bacteria and multiple sclerosis. Dr. Jennifer Linden, who presented the data on behalf of her Weill Cornell colleagues at the 2014 American Society for Microbiology Meeting, reported that the epsilon toxin (ETX) - which is derived from a strain of the bacteria Clostridium perfringens - caused MS-like damage in the brains of lab mice.
Clostridium perfringens is a common cause of food poisoning in developed countries. It can be found in poorly prepared meat and poultry products, but is also found as a natural component of decaying vegetation, soil, and marine sediment. There are five subtypes of C. perfringens, two of which (types B and D) produce the highly potent ETX which can enter and cause damage to the central nervous system. Although the exact cause of MS is unknown, researchers have long suspected that genetic, lifestyle and environmental factors all play a significant role. The mode of action of these particular bacterial strains adds them to the list of potential environmental triggers of MS disease.
Last year, the C. perfringens type B strain was isolated from a 21-year old female living with MS. This was the first time that a human was known to carry type B, which is typically found in grazing animals like cows and sheep. This observation lead to further experiments evaluating the role of C. perfringens in the development of MS, the results of which were published last October in the journal PLoS ONE.
Study and results:
The published study assessed the prevalence of the non-harmful strain of C. perfringens – type A – in people with MS compared with healthy individuals. Results showed that 52% of the healthy individuals carried type A, compared with 23% of people with MS. Researchers propose that the absence of this commensal bacterial strain may provide an environment for the growth and survival of the toxin-producing type B strain which would no longer have to compete for resources.
The study also looked for antibodies against ETX toxin in fluid samples from people with MS and healthy individuals. This would determine whether they have been infected with C. perfringens type B. Researchers found that 10% of people with MS and 1% of healthy individuals possessed antibodies for ETX, which indicates prior exposure to ETX in the MS population.
Finally, the research team performed a series of experiments which demonstrated the ability for ETX to attach to white matter which contains myelin – the substance that is damaged in MS. Previous studies have shown that when administered to animals, ETX can disrupt the blood brain barrier (BBB) and create tissue damage and death of oligodendrocytes once inside the central nervous system. In this study, researchers were able to show that ETX was found in areas that had myelin.
Although the ETX toxin-producing C. perfringens type B strain was found in a person with MS, this data is still preliminary and warrants further work to determine the role of the bacterium as an environmental trigger of the disease. This study also calls into question the nature of MS as an autoimmune disease. According to the article, in the very early stages of MS when lesions are first appearing, immune cells are absent in the central nervous system, and only damage to the BBB and death of oligodendrocytes is observed. This means that the initial tissue damage is caused by another culprit. Because C. perfringens type B possesses the ability to enter the central nervous system and cause damage to myelin and the cells which produce myelin, this bacteria has become an important piece of the puzzle with regards to the cause of MS. The MS Society will continue to monitor the emergence of new data, including data from the new study presented at the conference, as it becomes available.
Rumah KR et al. Isolation of Clostridium perfringens Type B in an Individual at First Clinical Presentation of Multiple Sclerosis Provides Clues for Environmental Triggers of the Disease. PLOS ONE 2013 October 15; 8(10):1-9.