Epsilon Toxin May be an Environmental Trigger for Multiple Sclerosis

Study results show that epsilon toxin, produced by a common foodborne bacterium, attacks the brain's myelin-producing cells and targets other cells associated with inflammation in MS.

Previous research has suggested that a toxin produced by a common foodborne bacterium may be a trigger for multiple sclerosis (MS). Study results presented by Jennifer Linden, PhD, and colleagues from Weill Cornell Medical College at the 2014 ASM Biodefense and Emerging Diseases Research Meeting provided further evidence that supports this hypothesis.

Their research showed that epsilon toxin produced by some strains of the spore-forming bacterium Clostridium perfringens may be an environmental trigger of MS.

In a news release accompanying publication of the study results, Linden explained that the study provided evidence that supports epsilon toxin’s ability to cause blood brain permeability, and also showed that epsilon toxin kills oligodendrocytes, which form myelin in the brain. These are the same cells that are damaged by MS lesions.

The research also showed that epsilon toxin "targets other cells types associated with MS inflammation such as the retinal vascular and meningeal cells. Epsilon toxin may be responsible for triggering MS,” Linden said.

She noted that the research team had initially assumed epsilon toxin would target only brain endothelium cells and oligodendrocytes. However, they observed that it also bound to and killed meningeal cells, "which was exciting because it provides a possible explanation for meningeal inflammation and subpial cortical lesions exclusively observed in MS patients, but not fully understood.”

These finding could be significant because, according to Linden, confirmation that epsilon toxin is an environmental trigger for MS would provide a target for the development of “a neutralizing antibody or vaccine directed against epsilon toxin” that might halt the progression of the disease or prevent it from developing.

In prior research, Linden and colleagues had discovered the presence of C. perfringens type B in a 21-year-old woman diagnosed with MS who was experiencing flare-ups. This was the first time that C. perfringens type B had been detected in a human.

Both C. perfringens type B and type D (which had previously been found in two people) produce epsilon toxin. C. perfringens type A is commonly found in the human gastrointestinal tract and thought to be mostly harmless.

According to a news release from Weill Cornell Medical College, researchers investigated whether subtypes B or D exist in humans and if they are associated with MS by testing blood and spinal fluid samples from patients with MS and healthy controls for antibody reactivity to the epsilon toxin. They reported that “levels of epsilon toxin antibodies in MS patients were 10 times higher than in the healthy controls — the blood of only one out of 100 control participants showed an immune reaction to the toxin.”

They also examined stool samples from MS patients and healthy controls enrolled in the study, and found that “52 percent of healthy controls carried the A subtype compared to 23 percent of MS patients.” The researchers said this was potentially 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.”

The scientists speculated that C. perfringens type B or D may lie dormant in the gastrointestinal tract of infected humans for long periods of time, undergoing episodic periods of growth, during which it releases epsilon toxin into the patient’s system.

They said these findings suggest that several approaches to treatment are possible, including a vaccine, small-molecule drugs that prevent the toxin from binding to its receptor, and a combination of probiotics that include bacteria that “compete with and destroy, C. perfringens types B and D.”