Study Identifies New Pathway to Guide Therapies for MS

The connection between the gut and the brain is complex and byproducts of microorganisms living in the gut are able to influence the progression of neurodegenerative diseases. However, researchers from Brigham and Women’s Hospital (BWH) have defined a new pathway that may help guide therapies for multiple sclerosis (MS) and other neurologic diseases.

The study, recently published by Nature, evaluated the influence gut microbes have on microglia and astrocytes—two types of cells that play a significant role in the central nervous system (CNS).

Microglia are responsible for scavenging the CNS and removing plaques, damaged cells, and any other materials that need to be removed; however, microglia can also secrete compounds that induce neurotoxic properties on astrocytes. This is believed to contribute to many neurologic diseases, such as MS, according to the study.

“These findings provide a clear understanding of how the gut impacts central nervous system resident cells in the brain,” said author Francisco Quintana, PhD, of the Ann Romney Center for Neurologic Diseases at BWH. “Now that we have an idea of the players involved, we can begin to go after them to develop new therapies.”

The researchers used a mouse model of MS to examine gut microbes and the effects of changes in diet. The results showed that compounds from the breakdown of tryptophan can cross the blood-brain barrier and activate an anti-inflammatory pathway that limits neurodegeneration.

When the researchers studied human MS, rather than mouse models, they found evidence of the same pathway.

“Activation of this same pathway has recently been linked to Alzheimer’s disease and glioblastoma,” read the press release. “The Ann Romney Center for Neurologic Diseases, of which Quintana is a part, brings experts together to accelerate treatment for these diseases, as well as multiple sclerosis Parkinson’s disease and ALS (Lou Gehrig’s disease).”

This study is the first to report on how microbial products may act directly on microglia to prevent inflammation.

“It is likely the mechanisms we’ve uncovered are relevant for other neurologic diseases in addition to multiple sclerosis,” said Quintana. “These insights could guide us toward new therapies for MS and other diseases.”

Quintana and his fellow researchers intend to conduct future studies involving the connections to neurologic diseases. They are currently working to optimize small molecules and probiotics to identify other elements that participate in the pathways and potentially new therapies.

Reference:

Rothhammer V, Borucki D, Tjon E, et al. Microglial control of astrocytes in response to microbial metabolites. Nature. 2018;557:724-728. nature.com/articles/s41586-018-0119-x. Published May 16, 2018. Accessed May 31, 2018.