Clostridium perfringens could trigger multiple sclerosis

Epsilon toxin is produced by certain strains of Clostridium perfringens and scientists from Weill Cornell Medical College revealed lab tests in mice caused MS-like damage in the brain.

MS is thought to be triggered by genetic and environmental factors but the exact environmental trigger is not known, said the researchers.

Pathogen effect​

The US Centers for Disease Control and Prevention (CDC) estimates that non-epsilon toxin producing C. perfringens strains cause nearly a million cases of foodborne illness each year.

C. perfringens is commonly found on raw meat and poultry and some strains produce a toxin in the intestine that causes illness, said the CDC.

Multiple sclerosis is an inflammatory disease of the central nervous system characterized by blood brain (BBB) permeability and demyelination, a process in which the insulating myelin sheaths of neurons are damaged.

“We provide evidence that supports epsilon toxin's ability to cause BBB permeability and show that epsilon toxin kills the brain's myelin producing cells, oligodendrocytes; the same cells that die in MS lesions​," said Jennifer Linden of Weill Cornell Medical College, who presented the work at the ASM Biodefense and Emerging Diseases Research Meeting.

Type B strain found​

Linden and her colleagues discovered C. perfringens type B (a strain that was not known to infect humans) in a 21-year-old woman experiencing a flare-up of her MS, in a study published in October last year (see below).

To test the hypothesis, they studied the behavior of the toxin in mice and which cells it targeted.

It was found that the toxin targeted the brain cells associated with MS pathology.

They tested samples of local foods for the presence of C. perfringens and the toxin gene. Of the 37 food samples, 13.5% were positive for bacteria and 2.7% were positive for the epsilon toxin gene.

Epsilon toxin​

C. perfringens types B and D carry a gene (epsilon toxin) that emits a protoxin (a non-active precursor form of the toxin) which is turned into the epsilon toxin within intestines of grazing animals.

The epsilon toxin travels through the blood to the brain, where it damages brain blood vessels and myelin, the insulation protecting neurons, resulting in MS-like symptoms in the animals.

While the D subtype has only been found in two people, based on prior studies by other investigators, the B subtype had never been found in humans.

“This bacterium produces a toxin that we normally think humans never encounter. 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 the researchers.

A high intake of dietary salt has been linked​ to amplifying and triggering autoimmune responses that can lead to MS, while high levels of Vitamin D may be associated with a lower risk of MS progression​.

Source: PLoS ONE

Online ahead of print, DOI: 10.1371/journal.pone.0076359​

“​Isolation of Clostridium perfringens Type B in an Individual at First Clinical Presentation of Multiple Sclerosis Provides Clues for Environmental Triggers of the Disease”​

Authors: Kareem Rashid Rumah, Jennifer Linden, Vincent A. Fischetti, Timothy Vartanian