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Research advancing understanding of what causes MS disease.

New Research Advances Understanding of What Causes MS Disease

The Mystery of Autoimmune Diseases

The mystery that faces those with multiple sclerosis and any autoimmune disorder: what triggers the disease? On a basic level, autoimmune disease occurs because the body’s natural defenses, the immune system, attack the body’s healthy tissue. But the answers to “how” and “why” remain elusive to scientists, physicians, and those dealing with autoimmune disease.

By way of background, MS occurs when the immune system attacks the healthy tissue in the central nervous system, composed of the brain and spinal cord. The resulting damage to myelin, the protective sheath that covers nerve fibers, causes communication problems between the brain and the rest of the body.

MS and Gut Dysbiosis

It has long been suspected that environmental factors can contribute to the development of MS. As discussed in BeCare Link’s previous blogs “Managing MS: Why Gut Health is So Important” and “Diet and MS: What You Should Know,” an alteration of the gut bacteria lining the gut (called gut dysbiosis) is commonly seen in MS patients. However, it has not been known which bacteria may trigger immune dysfunction. Investigators at Weill Cornell Medicine, headed by one of BeCare MS Link’s founders, MS expert Dr. Timothy Vartanian, have identified a toxin-producing bacteria that abundantly colonizes the gut of MS patients. This toxin alters the immune response to tissues in the central nervous system. 

Weill Cornell Study on Gut’s Toxin-Producing Bacteria

The Weill Cornell scientists used the laboratory technique of PCR, a DNA analysis, to study these bacteria. Quantitative PCR detection revealed that MS patients had a greater concentration of epsilon toxin (ETX)-producing strains of C. perfringens in their gut biomes compared to healthy controls.

The study incorporated active immunization modeling, the most widely applied mouse model of multiple sclerosis. (Source). Experimental autoimmune encephalomyelitis (EAE) was induced in mice by exposing them to ETX. EAE is an experimentally induced autoimmune attack on the brain and spinal cord. Unlike other toxins studied in the past, the ETX toxins produce inflammatory demyelination in the neuroanatomical distributions where MS lesions are found. In other words, the ETX toxin caused damage to the central nervous system’s myelin sheaths (the white matter of the brain) in the same anatomical sites damaged in MS — corpus callosum, thalamus, cerebellum, brainstem, and spinal cord. Therefore, the investigators believe these bacteria may trigger inflammatory demyelination due to circulating immune cells that attack myelin (myelin autoreactive lymphocytes).

The Role of the Neurotoxin C. perfringens ETX

The neurotoxin C. perfringens ETX, found in the bloodstream, targets the lining of the central nervous system’s blood vessels called endothelial cells. As a result, this neurotoxin can disrupt the “Blood-Brain Barrier.” The blood-brain barrier is a crucial immunological barrier that protects the central nervous system from infection caused by bacteria, fungi, viruses, or parasites circulating in the bloodstream. (Source).

C. perfringens is ever-present. The bacterium can be found in our food chain, sewage, marine sediment, soil, and the intestinal tract of humans, fish, birds, and other mammals. Once a person has environmental exposure and oral ingestion of the spores of C. perfringens, colonization of the small intestine occurs. The amount of colonization is thought to be mediated by several factors: genetics, the condition of the person’s gut microbiome, and other factors, including previous antibiotic use.

Interestingly, ETX, circulating in the bloodstream, has access to the vessels in all tissues, but it binds specifically to the brain’s endothelial cells, critical constituents of the blood-brain barrier. This cellular affinity of ETX results because endothelial cells have a greater concentration of ETX receptors (proteins that bind to the ETX).

A Promising Conclusion?

The study’s findings suggest that ETX-producing C. perfringens strains are biologically plausible culprits in triggering the development of the inflammatory demyelination that is a hallmark of multiple sclerosis. This promising explanation of “how” and “why” MS occurs may lead to clues on how to prevent MS in the first place.  The potential to create novel avenues of MS prevention by blocking ETX through vaccines, novel medications, or attention to genetic makeup is generating great excitement and hope for scientists and patients alike.

You can read the complete study in The Journal of Clinical Investigation here.

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