Bacterial Toxin May Trigger Multiple Sclerosis

Sue Hughes

Researchers have identified a bacterial toxin that they believe may be a trigger for multiple sclerosis (MS).

Their study, published in the October issue of PLoS ONE, is the first to identify the culprit bacterium, Clostridium perfringenstype B, in humans, and to single out the toxin it produces — known as epsilon toxin — as a probable MS trigger.

The researchers, from the Weill Cornell Medical College and The Rockefeller University in New York, New York, describes discovery of C perfringens type B in a 21-year-old woman who was experiencing a flare-up of her MS.

“That we identified this bacterium in a human is important enough, but the fact that it is present in MS patients is truly significant because the toxin targets the exact tissues damaged during the acute MS disease process,” said lead author, Kareem Rashid Rumah, an MD/PhD student at Weill Cornell Medical College.

For the study, the researchers screened serum and spinal fluid from 30 patients with MS and 31 healthy controls. They found that 10% of the patients with MS had antibodies to an epsilon toxin compared with just 1% of controls.

Senior investigator, Timothy Vartanian, MD, Weill Cornell Medical College, commented to Medscape Medical News: “We know from the veterinary literature that if animals are vaccinated against C perfringens type B, their immunity drops off very quickly. So the 10% figure is probably lower than the real incidence. We believe the exposure is much higher than the seroreactivity is telling us.”

The team also examined stool samples from both patients with MS and healthy controls enrolled in the HITMS (Harboring the Initial Trigger of Multiple Sclerosis) clinical study and found that 52% of healthy controls carried the A subtype compared with 23% of patients with MS.

“This is important because it is believed that the type A bacterium competes with the other subtypes for resources, so that makes it potentially protective against being colonized by epsilon toxin–secreting subtypes and developing MS,” Dr. Vartanian noted. 

Evidence Supporting a Trigger

He says substantial evidence supports the idea of an environmental trigger necessary for MS to begin. “There are many datasets that point to this.” He gives the example of the situation in the Faroe Islands.

“The population of the Faroes has the same ancestry as that of the Scandinavian countries, where there has been a high incidence of MS. But there was no case of MS documented in the Faroes until 1943, when British troops occupied the country. This coincided with the first of 4 documented MS epidemics within native Faroe people.”

The other piece of information that points to a trigger, Dr. Vartanian explained, is the pathology of the very first lesions at the earliest stages of the disease, which shows disruption of the normal integrity of the blood-brain barrier, oligodendrocyte apoptosis with preservation of myelin, and early microglial activation, but no T cells or B cells. “This suggests that the initial lesions are not formed by an autoimmune response but rather by a toxin or virus targeting oligodendrocytes.”

“While it is clear that new MS disease activity requires an environmental trigger, the identity of this trigger has eluded the MS scientific community for decades,” Dr. Vartanian says.

He noted that it has previously been suggested that MS may be related in some way to sheep and that organisms commonly found in sheep may be a trigger. C perfringens type B is one such organism, and he is proposing that the toxin it produces could be the trigger.

“C perfringens B is found in soil and is not normally present in humans. It can live the gastrointestinal tract of grass-eating animals, where it can grow fast and make a toxin that causes neurological symptoms. In humans, who have a linear GI [gastrointestinal] tract, it does not grow well. Our hypothesis is that in some environmental conditions, this bacterium takes up residence in the human gut and makes this toxin.”

Continue Reading

Visit our MS Learning Channel on YouTube: http://www.youtube.com/msviewsandnews