Investigating the byproducts of gut bacteria gives fresh insight into how the microbiome influences inflammation in the brain and its potential role in neurological conditions.
Gut bacteria illustration
Gut bacteria (depicted here) appear to play a role in brain inflammation.

According to recent research, gut bacteria play a part in pretty much every facet of physiology, in both health and disease.

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Gut bacteria have been shown to play a role in everything from diabetes to obesity, and from depression to schizophrenia.

It is these links with mental health and the nervous system in general that fascinates Francisco Quintana, Ph.D., from the Ann Romney Center for Neurologic Diseases at Brigham and Women’s Hospital in Boston, MA.

Quintana and his team recently published a paper in the journal Nature, outlining how the gut-brain connection might work on a cellular level. Their findings have implications for many neurological conditions, including multiple sclerosis (MS).

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Using both animal models and human cells, they have spent years investigating the three-way interactions between the brain, gut, and immune system.

“These findings,” exlains Quintana, “provide a clear understanding of how the gut impacts central nervous system resident cells in the brain.”

Now that we have an idea of the players involved, we can begin to go after them to develop new therapies.”

Francisco Quintana, Ph.D.

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Microglia and astrocytes

The team’s publication focuses on how gut bacteria interact with two types of brain cell: microglia and astrocytes.

Microglia are a major player in the central nervous system’s immune response; they remove dead and damaged cells.

Astrocytes are star-shaped cells that provide support to nerve cells. Microglia are known to release certain neurotoxins that damage astroglia. This damage is thought to play a role in a number of neurologic conditions by causing inflammation in the brain.

In the new study, researchers used a mouse model of MS. Although earlier studies have described how byproducts from micro-organisms in the gut might promote brain inflammation, this study was the first to show how gut bacteria’s products can act directly on microglia to reduce inflammation.

More specifically, the byproducts produced by gut bacteria when they break down tryptophan were shown to influence microglia, thereby reducing inflammation in the brain. Tryptophan is an amino acid found in many foods, including turkey, cheese, and chickpeas.

The breakdown products of this amino acid, the study authors demonstrated, could travel across the blood-brain barrier, activating an anti-inflammatory pathway that protects against neurodegeneration.

As an extension to the study, the scientists looked at brain tissue from humans with MS and found similar molecules and pathways. This pathway has also been shown to be involved in Alzheimer’s disease and glioblastoma, so the ramifications of this line of inquiry could be wide-reaching.

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