SUMMARY

• Researchers were able to trace a set of interactions that help explain how diet and the gut bacteria influenced by diet may act on the immune system to limit inflammation and nerve damage in mice. The team also found preliminary evidence verifying that similar interactions influence human cells.
• The study, supported by the National MS Society, the International Progressive MS Alliance and others, provides important clues for better understanding the gut-brain connection, and could lead to new treatment approaches for MS.
• The international team, led by Dr. Francisco Quintana (Brigham and Women’s Hospital, Harvard Medical School) published their findings in the journal Nature online on May 16, 2018.

DETAILS

Background: MS involves immune-system attacks and inflammation in the brain and spinal cord. The gut, including the small and large intestine, is the largest immune organ in mammals, including people. Each of us has millions of “commensal” bacteria living within our guts. Most of these bacteria are harmless as long as they remain in the inner wall of the intestine. They play a critical role in our normal physiology, and accumulating research suggests that they are critical in establishing and maintaining immune balance by the molecules they release. Differences have been detected between the gut bacteria from people with MS compared to people without MS.

The effects of diet on gut bacteria and on immune system activity is difficult to tease out, and there is much that is not yet understood. Dr. Francisco Quintana and an international team of collaborators set out to understand the links between immune activity in mice with the MS-like disease EAE, and dietary components that are processed by gut bacteria, and how those interactions impact the activity of cells within the brain and spinal cord. Dr. Quintana leads one of three Collaborative Networks supported by the International Progressive MS Alliance.

This study focused on possible interactions between gut bacteria and glial cells, which are the most abundant cells in the central nervous system (brain and spinal cord) and play major roles in both health and disease. Specifically, the study focused on the interactions of two types of glial cells: microglia and astrocytes.

The Study: In a series of laboratory studies, the researchers investigated activities that could influence whether microglia increase or decrease inflammation in the brain. They explored the role of a protein called AHR (aryl hydrocarbon receptor). Dr. Quintana’s team found that eliminating AHR from microglia worsened the MS-like disease EAE in mice, and increased nerve damage. EAE inflammation was then reduced by adding the amino acid tryptophan in the diet. This reduction of inflammation was driven by the conversion of tryptophan by the gut bacteria into a substance that activates AHR. Activating AHR reduced the amount of pro-inflammatory molecules made by microglia and also suppressed molecules that regulate the contribution of astrocytes to brain inflammation.

The team also found preliminary evidence verifying that similar interactions influence human cells. They have plans for continuing this line of research to identify therapies or probiotics that can reduce inflammation to turn off or decrease disease activity.

Identifying components of this “gut-brain” connection and better understanding this complicated web of interactions with the immune system and nervous system provides important clues that could lead to new treatment approaches for MS and other neurodegenerative disorders like Alzheimer’s disease and glioblastoma.

The international team, led by Dr. Francisco Quintana (Brigham and Women’s Hospital, Harvard Medical School) published their findings in the journal Nature online on May 16, 2018.