Gut-Brain Axis − Future of MS Treatment?
The relationship between the gut microbiome and multiple sclerosis has been a major topic recently. How far has current science progressed in decoding this issue? A recent review article published in the journal Neuroscience Research summarizes the existing findings on the relationship of the gut microbiome to the etiopathogenesis and course of multiple sclerosis (MS).
As has been proven, the gut microbiome has the potential to significantly affect the health status of its host, and the development of laboratory methods has enabled the exploration of associations between some types of bacteria and specific diseases, such as Alzheimer's disease, amyotrophic lateral sclerosis, or Parkinson's disease.
Of Mice and Men
The first crucial work confirming the relationship between the gut microbiome and autoimmune CNS disease in a mouse model was published in 2008. A groundbreaking publication examining the gut microbiome of human patients was in 2015, comparing healthy controls and patients with relapsing-remitting MS (RRMS). In the gut microbiome of RRMS patients, there was a reduction in the representation of 19 bacterial species and an increase in two others. Fourteen of the 19 less represented species belonged to clostridia producing butyrate or propionate.
A significant reduction in these bacterial species suggests a depletion of short-chain fatty acids (SCFA) in the guts of MS patients. Butyrate not only induces regulatory T cells in the large intestine but also enhances remyelination in the CNS. Several studies have shown an improvement in clinical course with oral supplementation of butyrate or propionate in both animal models and human patients. The altered microbiome and subsequent depletion of SCFA production in the gut are therefore likely at least partly associated with a lowering of the threshold for the development and exacerbation of RRMS.
Microbiome and Progression − Are They Related?
In 2020, a study was published analyzing the gut microbiome of MS patients using metagenomic sequencing. Interesting differences were observed between RRMS and secondary progressive MS (SPMS), which aligns with the hypothesis that the transition to SPMS may be caused by changes in the gut microbiome. However, research into the gut microbiome of SPMS patients is still in its early stages.
Many Theories, Long Road Ahead
Theories explaining the influence of the gut microbiome on autoimmune CNS diseases are numerous. Besides the above, molecular mimicry (so far demonstrated in a mouse model), greater binding of intestinal IgA to certain types of bacteria, or the impact of oxidative stress may also contribute to this association.
The path to clarifying the gut-brain axis relationship is still largely ahead of us. However, its exploration could lead to a better understanding of the causes and improved prevention options for MS, and bring us to completely innovative and groundbreaking therapeutic approaches.
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Source: Takewaki D., Yamamura T. Gut microbiome research in multiple sclerosis. Neurosci Res 2021; 168: 28−31, doi: 10.1016/j.neures.2021.05.001.
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