How the gut influences neurologic disease

May 16, 2018, Brigham and Women's Hospital
Credit: CC0 Public Domain

A study published this week in Nature sheds new light on the connection between the gut and the brain, untangling the complex interplay that allows the byproducts of microorganisms living in the gut to influence the progression of neurodegenerative diseases. Investigators from Brigham and Women's Hospital (BWH) have been using both animal models and human cells from patients to tease out the key players involved in the gut-brain connection as well as in the crosstalk between immune cells and brain cells. Their new publication defines a pathway that may help guide therapies for multiple sclerosis and other neurologic diseases.

"These findings provide a clear understanding of how the gut impacts central nervous system resident cells in the ," said corresponding author Francisco Quintana, Ph.D., 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 new research focuses on the influence of on two types of cells that play a major role in the central nervous system: microglia and astrocytes. Microglia are an integral part of the body's immune system, responsible for scavenging the CNS and getting rid of plaques, damaged cells and other materials that need to be cleared. But microglia can also secrete compounds that induce neurotoxic properties on the star-shaped brain known as astrocytes. This damage is thought to contribute to many , including .

Brigham researchers have previously explored the gut-brain connection to gain insights into multiple sclerosis. Although some studies have examined how byproducts from organisms living in the gut may promote inflammation in the brain, the current study is the first to report on how microbial products may act directly on microglia to prevent inflammation. The team reports that the byproducts that microbes produce when they break down dietary tryptophan—an amino acid found in turkey and other foods—may limit inflammation in the brain through their influence on microglia.

To conduct their study, the research team examined gut microbes and the influence of changes in diet in a mouse model of multiple sclerosis. They found that compounds resulting from the breakdown of tryptophan can cross the blood-brain barrier, activating an anti-inflammatory pathway that limits neurodegeneration. The researchers also studied human multiple sclerosis brain samples, finding evidence of the same pathway and players.

Activation of this same pathway has recently been linked to Alzheimer's and glioblastoma. 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).

"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 colleagues plan to further study the connections to neurologic diseases, and are also optimizing small molecules as well as probiotics to identify additional elements that participate in the pathway and new therapies.

Explore further: Exploring the gut-brain connection for insights into multiple sclerosis

More information: Veit Rothhammer et al, Microglial control of astrocytes in response to microbial metabolites, Nature (2018). DOI: 10.1038/s41586-018-0119-x

Related Stories

Exploring the gut-brain connection for insights into multiple sclerosis

May 9, 2016
New research by investigators at Brigham and Women's Hospital (BWH) suggests that bacteria living in the gut may remotely influence the activity of cells in the brain that are involved in controlling inflammation and neurodegeneration. ...

Researchers find molecular trigger for brain inflammation

April 27, 2017
Brain inflammation is a key component of multiple sclerosis, Alzheimer's, Parkinson's, ALS, and most other major neurodegenerative diseases. How inflammation starts, how it's sustained, and how it contributes to these diseases ...

An immunological memory in the brain

April 11, 2018
Inflammatory reactions can change the brain's immune cells in the long term—meaning that these cells have an "immunological memory." This memory may influence the progression of neurological disorders that occur later in ...

Identifying the dangers of chronic stress on multiple sclerosis

February 6, 2018
New research reveals how chronic stress and tiny brain inflammations cause fatal gut failure in a multiple sclerosis mouse model.

New disease model to facilitate development of ALS and MS therapies

April 17, 2018
Researchers at Karolinska Institutet in Sweden have developed a new disease model for neurodegenerative diseases such as ALS and MS that can be used to develop new immunotherapies. The model is described in a publication ...

Recommended for you

Age-related increase in estrogen may cause common men's hernia

October 16, 2018
An age-related increase in estrogen may be the culprit behind inguinal hernias, a condition common among elderly men that often requires corrective surgery, according to a Northwestern Medicine study was published Oct. 15 ...

New findings cast light on lymphatic system, key player in human health

October 16, 2018
Scientists at the Oklahoma Medical Research Foundation have broken new ground in understanding how the lymphatic system works, potentially opening the door for future therapies.

New model suggests cuffless, non-invasive blood pressure monitoring possible using pulse waves

October 16, 2018
A large team of researchers from several institutions in China and the U.S. has developed a model that suggests it should be possible to create a cuffless, non-invasive blood pressure monitor based on measuring pulse waves. ...

Discovery of inner ear function may improve diagnosis of hearing impairment

October 15, 2018
Results from a research study published in Nature Communications show how the inner ear processes speech, something that has until now been unknown. The authors of the report include researchers from Linköping University, ...

Team's study reveals hidden lives of medical biomarkers

October 12, 2018
What do medical biomarkers do on evenings and weekends, when they might be considered off the clock?

Widespread errors in 'proofreading' cause inherited blindness

October 12, 2018
Mistakes in "proofreading" the genetic code of retinal cells is the cause of a form of inherited blindness, retinitis pigmentosa (RP) caused by mutations in splicing factors.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.