Toxin in Gut Bacteria may be the Culprit Behind Multiple Sclerosis

Toxins from gut bacteria may trigger the relapse of multiple sclerosis.

Highlights:

Multiple sclerosis (MS) is a chronic condition that affects the central nervous system
The exact cause of MS is unknown, but genetic and environmental factors are suspects
A recent study has found that a toxin from common gut bacteria may trigger MS in people with a genetic susceptibility

The cause of multiple sclerosis (MS) is often unknown, although experts believe that genetic susceptibility and environmental factors may contribute to the onset of the condition.

In a recent animal study, researchers from the Brain and Mind Research Institute at Weill Cornell Medicine have 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 ().

“There are many mysteries about 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.

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

2.8 million people globally 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 like muscle weakness, numbness and tingling, bladder and bowel problems, vision problems, fatigue, dizziness and vertigo, and muscle spasms with pain.

The most common form of MS, relapsing-remitting MS, which causes 85% of cases, is usually characterized by episodes of new or increasing symptoms, and periods, where symptoms lessen or disappear.

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‘Toxin released by gut bacteria could be a reason for onset of multiple sclerosis.’

Relationship of Gut Microbiota with Multiple Sclerosis

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 protozoa.

These microbes are generally useful and important for our health. However, problems can occur if the microbiota gets out of balance — known as dysbiosis.

Previous studies have suggested changes in the microbiota may contribute to some autoimmune disorders ().

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How Epsilon Toxin Affects Multiple Sclerosis

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 perfringens than healthy controls. C. perfringens produces the epsilon toxin, which opens the blood vessels in the brain, allowing inflammatory cells to access the CNS.

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. The researchers took fecal samples from people with MS and healthy controls. They analyzed these samples using polymerase chain reaction (PCR) 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. Additionally, 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 MS — as the mice that were given PTX. The ETX mice also had lesions in the white matter bundle of the corpus callosum, which were not seen in the other mice.

The two hemispheres in the brain are connected by a thick bundle of nerve fibers called the corpus callosum that ensures both sides of the brain can communicate and send signals to each other.

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Treatments for Epsilon Toxin

C. perfringens produces epsilon toxin only when it is in the rapid growth (exponential) 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.

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.

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Importance of a Healthy Microbiome

Previous studies have shown that the gut microbiome may be an important factor in the progression of MS. A 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 recognized, 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.

References:

Epsilon toxin-producing Clostridium perfringens colonize the MS gut and epsilon toxin overcomes immune privilege - (https://www.jci.org/articles/view/163239)
Rising prevalence of multiple sclerosis worldwide: Insights from the Atlas of MS, third edition - (https://pubmed.ncbi.nlm.nih.gov/33174475/)
The gut microbiome: Relationships with disease and opportunities for therapy - (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6314516/)
Microbiota in health and diseases - (https://www.nature.com/articles/s41392-022-00974-4)

Source-Medindia