Gut Microbiome

New Directions in MS Research: New Therapeutic Approaches

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The gut microbiome is the milieu of bacteria and other microbes found in the gastrointestinal (GI) tract. It is a major component of the body’s immune system, and a growing body of evidence suggests that the presence and number of various microbes in the microbiome may affect the course of MS.

In one recent study, Italian investigators explored whether changes in the mix of microbes that make up the microbiome were associated with the onset of MS as indicated by an initial episode of demyelination. The researchers examined stool and blood samples from 18 recently diagnosed MS patients and 18 healthy volunteers who were matched for age, sex, diet, and lifestyle.

Using DNA analysis and other sophisticated tests, those investigators determined that at the onset of MS, the gut microbiomes of patients were markedly different from those of healthy volunteers. People with MS had fewer different types of microbes than healthy volunteers, and a reduced presence of butyrate-producing bacteria that are believed to have an impact on various immune system cells. They concluded, “Our data indicate that gut microbial dysbiosis [an imbalance of the bacteria in the gut] exist at the onset of MS and could be associated with the autoimmune response in the periphery, highlighting the importance of gut microbiome in the etiology of MS.”92

Another study found that a toxin potentially associated with the formation of central nervous system (CNS) lesions was present in the gut microbiome of 21% of people with MS studied, but in none of the healthy volunteers studied. Researchers used sophisticated tests to identify the presence and genetic characteristics of Clostridium perfringens epsilon toxin in fecal samples from people with MS and matched healthy volunteers. They noted that the toxin is an attractive candidate for new lesion formation because it targets both CNS endothelial cells and oligodendrocytes/myelin.93

Based on the fact that one in five people with MS had a specific type of the toxin in their gut microbiome, while it was absent from all of the healthy volunteers participating in the study, the researchers concluded, “Colonization of the gut by C. perfringens type B is statistically associated with MS. While two epsilon toxin-producing C. perfringens strains (type B and type D) exist in nature, thus far we have identified only type B strains from MS subjects.”93

Meanwhile, another group of investigators is exploring whether borrowing an unusual technique from their infectious disease colleagues may help change the gut microbiome of people with MS. Positive results in terms of altering the microbiome’s composition would set the stage for pursuing the larger questions of whether those changes affect the course of MS.94

The technique is called fecal microbial transplantation, or FMT. It involves using a rectal enema to transfer fecal material from a healthy person into the GI system of someone with MS to see if this intervention changes the mix of microbes present in the gut of the MS patient. Infectious disease specialists have employed FMT to treat people suffering from colitis due to infection with Clostridium difficile, a bacterium that can cause severe diarrhea and other complications.

The single-site, randomized, open-label study will randomize 40 people with MS into two groups of 20 subjects each. Participants in the early-intervention group will receive FMT by rectal enema, while the other group will receive standard MS treatment for the first six months of the study. Thereafter, the earlyintervention group no longer will receive FMT, while the second group will begin a six-month course of FMT. The study’s primary outcome will be the level of cytokines – inflammatory molecules – in the peripheral blood. Ten healthy volunteers will serve as a reference control group for cytokine levels. Secondary outcomes are blood DNA bacteria and gut permeability. MRI scans of the head also will be obtained as a means of assessing safety.

At the time that investigators presented an update on their research, 16 patients had been enrolled in the study. The participants had experienced MS symptoms for an average of 18 years, and 11 of the 16 were using a disease-modifying therapy. Six of the participants had begun receiving fecal microbial transplants, with a total of 24 interventions performed in those patients. No serious adverse events had been reported.

The investigators stated, “This proof of concept, first in humans, independent pilot study will shed light on the relationships between gut bacteria and MS. We aim to explore FMT feasibility in MS and its possible impact on disease inflammation. Moreover, we hope that these study results can guide future large-scale researches.”94

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