Produced by a bacterial toxin in the gut – specifically, epsilon toxin Clostridium perfringens Bacteria in the intestinal tract may be a major environmental driver of multiple sclerosis (MS), according to a recent study.
After finding higher amounts of the toxin in stool samples from MS patients than healthy people, scientists determined that epsilon disease-prone mice were capable of producing MS symptoms.
In fact, according to Timothy Vartanian, MD, PhD, chief of multiple sclerosis and neuro-immunology in the Department of Neurology at NewYork-Presbyterian/Weill Cornell Medical Center, “Epsilon toxin acts at the very early stages of MS lesion formation.”
“A treatment that neutralizes epsilon toxin could halt new disease activity in our patients, much more effectively than current treatments that suppress or modulate the immune system,” Vartanian, also one of the study’s co-senior authors, said. Weill Cornell press releaseAdding, “Immediately, we are driven by a sense of urgency to find more effective and safer therapeutics for people with MS.”
study,”Epsilon toxin producer Clostridium perfringens MS colonizes the gut and epsilon toxin overcomes the immune system” was published in Journal of Clinical Investigation.
Investigating the bacterial toxin epsilon in MS
The gut microbiome, consisting of the collection of microbes living in the intestinal tract, has been increasingly linked to MS in recent years. An imbalance of these microbes—called gut dysbiosis—is frequently observed in MS patients and has been linked to more severe disease in preclinical models.
For patients with an underlying genetic susceptibility to MS, it is possible that changes in the gut microbiome may be the environmental trigger that prompts the disease to eventually develop. Nevertheless, the specific bacteria that may drive this association have not been uncovered and have been the focus of recent research studies.
c. Perfringens It is an intestinal bacterium that humans are widely exposed to through pets and food sources. It releases epsilon toxin, known as ETX, a neurotoxin that selectively targets cells of the blood-brain-barrier (BBB).
The BBB works to prevent the passage of potentially harmful substances from the bloodstream into the brain. By targeting its cells, ETX reduces the integrity of that barrier, preferring to leak substances that it normally drives MS like immune cells that don’t let it through.
As such, ETX-production has a high abundance c. Perfringens An environmental MS trigger in the gut, according to a US-based research team.
While other studies of the human microbiome have failed to find this link, it’s possible that earlier techniques weren’t sensitive enough to detect toxin-producing bacteria, they noted.
“Previous studies would use an approach where you could see the bacterial species that were there, but you didn’t actually see the toxins or some of the more functionally relevant parts of the species,” said Christopher Mason, Ph.D., a professor and co-author of the Weill Cornell Institute for Quantitative Prediction at World Quant. Director of the Initiative and one of the study’s co-senior authors.
Now, the team tested stool samples from MS patients and healthy people using a more sensitive DNA detection technique.
In doing so, they found that MS patients were significantly more likely to carry the ETX-product c. Perfringens than their healthy counterparts – and at a greater abundance.
Clinical trials are needed to test ETX in MS patients
The researchers next turned to a preclinical model in which mice’s immune systems were altered to predispose them to MS, but the animals only developed symptoms if they were treated with a toxin called pertussis—which targets the BBB and immune cells. allows to penetrate the brain.
When the scientists swapped pertussis for ETX, they found that the toxin induced clinical symptoms of the disease and led to demyelination in the brain and spinal cord that was more extensive than when pertussis was used, with the distribution of lesions typically seen in MS patients. match better.
Demyelination, a progressive loss of the substance (myelin) that surrounds and protects nerve cells, is a hallmark of MS.
ETX leads to infiltration of immune cells that normally reside in the circulation and do not enter the brain unless the BBB is compromised. It also induces the activity of genes involved in BBB dysfunction.
Weill Cornell co-author Gregory F. According to Sonnenberg, PhD, the study “advances a more relevant model for the study of MS,” but also “defines a new microbial-derived determinant,” which may inform MS development.
MS has many mysteries. … Clostridium perfringens And epsilon toxin may explain much of this mystery.
In addition to the role of ETX in MS onset, it may be involved throughout the course of the disease.
When ETX is produced episodically c. Perfringens There is a phase of high growth. The researchers noted that these episodes may correlate with periods of relapsing-remitting MS disease activity.
“MS has many mysteries,” says Vartanian. “Clostridium perfringens And epsilon toxin may explain many of these mysteries.”
Still, a clinical trial would be needed to test their role in MS patients, “as would environmental factors,” the team concluded.