Toxin from gut bacteria may trigger multiple sclerosis onset and relapse

Some 2.8 million people worldwide are living with MS, and the numbers are increasing.

ISLAMABAD, (Online) - Multiple sclerosis (MS) is a chronic condition of the nervous system. It most commonly affects young adults between the ages of 20 and 40 and is more often seen in women than men.

According to the Multiple Sclerosis International Federation (MSIF), some 2.8 million people worldwide are living with MS, and the numbers are increasing.

In this autoimmune disorder, a person’s immune system attacks the myelin sheath covering the nerve fibers. The damage leaves a scar or lesion, called ‘sclerosis’. These lesions occur most commonly in the central nervous system and lead to a range of symptoms, The most common form of MS, relapsing-remitting MS, which causes 85% of cases, is characterized by episodes of new or increasing symptoms, and periods, where symptoms lessen or, disappear.

The exact cause is still unknown, but scientists believe that genetic susceptibility and environmental factors may contribute to the onset of the condition.

“There are many mysteries to MS. Why do some people get MS and others don’t, despite similar or identical genetics? What accounts for the episodic nature of relapses and remissions? How is the central nervous system targeted and why myelin specifically?,” co-senior author Dr. Timothy Vartanian, a professor of neuroscience in the Feil Family Brain and Mind Research Institute at Weill Cornell Medicine, said.

Now, research led by scientists from the Brain and Mind Research Institute at Weill Cornell Medicine has found that epsilon toxin — produced by a bacterium found in the small intestine — may trigger the onset of MS and cause continuing symptoms.

The study is published in The Journal of Clinical Investigation.

“The development of MS is thought to be due to a combination of genetic and environmental factors. This very elegant study implicates a specific bacterial toxin as an environmental etiologic agent in MS.” — Dr. Barbara Giesser, neurologist and MS specialist at Pacific Neuroscience Institute at Providence Saint John’s Health Center in Santa Monica, California, speaking to Medical News Today

How the gut microbiota affects MS

The gut microbiota is made up of trillions of microbes that live in your digestive system. Most of the microbes are bacteria, but there are also viruses, fungi, and tiny, single-celled animals called protozoa.

These microbes are generally useful, and indeed vital, to our health. However, problems can occur if the microbiota gets out of balance — known as dysbiosis. Studies have indicated that changes in the microbiota may contribute to some autoimmune disorders.

Changes to the gut microbiota are common in people with MS. This new research suggests that people with MS are more likely to harbor one bacterium, Clostridium perfringensTrusted Source, than healthy controls. C. perfringens produces the epsilon toxinTrusted Source, which opens the blood vessels in the brain, allowing inflammatory cells to access the CNS.

What is the epsilon toxin?

“The researchers used novel and sensitive techniques to identify the presence of the bacterium, and then investigated how the toxin produced an MS-like disease in a mouse model.” — Dr. Barbara Giesser

The researchers took fecal samples from people with MS and healthy controls. They analyzed these samples using polymerase chain reaction (PCR)Trusted Source to detect the gene for producing epsilon toxin (ETX), which is found only in C. perfringens.

They found that 61% of the samples from people with MS contained the ETX gene, compared with only 13% of those from healthy controls.

Further to this, they found that the gut microbiota of people with MS was more likely to be colonized by ETX positive C. perfringens than that of age and sex-matched healthy controls.

They next tested the effect of ETX in mice known to be susceptible to developing MS symptoms. Some mice were injected with ETX; others were injected with a different toxin (PTX, which had previously been shown to induce MS-like symptoms).

The mice they injected with ETX developed demyelination in many areas of the CNS, in a similar pattern to that seen in people with MS.

They had twice as many lesions in the cerebellum — the part of the brain responsible for balance and coordination that is commonly affected in MSTrusted Source — as the mice that were given PTX. The ETX mice also had lesions in the white matter bundle of the corpus callosumTrusted Source, which were not seen in the other mice.

Treatments to target this toxin

“This study builds on the present body of what is known about the gut microbiome in persons with MS. It is known to be different than those of non-MS controls, and has been shown to respond to treatment with some disease-modifying therapies.” — Dr. Barbara Giesser

C. perfringens produces epsilon toxin only when it is in the rapid growth (exponentialTrusted Source) phase. If ETX is responsible for MS lesions, the researchers suggest, this would explain the episodic nature of the disease, with symptoms reducing when bacteria are not producing the toxin.

They conclude that they have found a strong clinical association between the bacterium, its toxin, and MS. This finding raises the possibility of treatments that target this pathway, as Dr. Giesser told MNT:

“The toxin helps immune cells gain access to the central nervous system. This suggests that treatments targeting the bacterium or the toxin might potentially be useful as disease-modifying therapies.”

However, the researchers note that clinical trials would be needed to test whether this will give rise to potential treatments for MS.

Why a healthy microbiome is important

Studies have suggested that the gut microbiome may be an important factor in the progression of MS. A 2017 review of several studies found that diet could be used to modify the gut microbiota and improve the course of MS.

The benefits of maintaining a healthy gut microbiota are increasingly recognizedTrusted Source, and this study adds further evidence that an unbalanced microbiota may contribute to disease development.

As well as potentially reducing the risk of MS, a healthful diet and lifestyle that encourages the growth of beneficial gut bacteria could reduce the risk of developing many health conditions.