New research has potentially opened up a new way to treat some of the most serious neurodegenerative diseases, including a form of dementia and the most common type of motor neuron disease. The study discovered a hidden link between the gut and neurodegenerative conditions affecting the brain.
Gut Bacteria and Sugar Processing
It specifically found that the bacteria within your gut and how it processes sugars could lead to inflammation contributing to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). These two conditions are closely related and can sometimes overlap because they both involve the deterioration of neurons in the brain, according to Science Alert. In ALS, this impacts muscle movement while in FTD, the neurons affected causes significant changes in behaviour, language and sometimes movement.
Scientists still are not sure what the root cause behind either condition is. This is what a team of researchers from Case Western Reserve University in the US set off to investigate.
Study Findings: Inflammatory Glycogen
Now published in the Cell Reports journal, the study found that a particular type of glycogen, which is a form of sugar, created by bacteria in the gut triggers a response from the immune system that causes inflammation and damage in the brain. Using mouse models, the study proved this leads to neuron death that contributes to conditions like ALS and FTD.
They believe the reason for this is the body detecting a potentially dangerous sugar, the inflammatory glycogen, and sends the immune system into overdrive to the point that it starts affecting the brain. One other things medical experts do know about ALS and FTD is that it can be caused a variation in one specific gene, but not everyone who has this variation always develops the disease. This gene also seems to act as a brake on glycogen.
Experimental Evidence
The researchers engineered mice without this gene, mimicking the effect that the variant has in humans. Then they tested the variety of gut bacteria in the mice and checked how their immune systems reacts.
One gut bacteria, Parabacteroides merdae, produces glycogen and when it was introduced to the mice it caused serious inflammation and a breakdown of the blood-brain barrier. They also tested stool samples of human patients with ALS and FTD, where they found high levels of inflammatory glycogen.
The paper notes: Our demonstration that microbes that accumulate inflammatory forms of glycogen are enriched in the gut of ALS patients suggests that microbial glycogen may be an important example among many environmental and lifestyle factors that interact with predisposing genotypes to contribute risk of ALS onset and progression.
Potential Treatment
The researchers went one step further and gave the affected mice an enzyme that breaks down glycogen. This treatment extended the lifespans of the mice and reduced their inflammation levels but it did not improve their motor performance.
More research is needed to confirm this as a potential treatment. The researchers plan to move the investigation beyond mouse models and look at human participants with different types of glycogen-producing bacteria.
Aaron Burberry, an assistant professor of pathology at Case Western Reserve University, said according to Science Alert: To understand when and why harmful microbial glycogen is produced, the team will next conduct larger studies surveying gut microbiome communities in ALS/FTD patients before and after disease onset.
Clinical trials to determine whether glycogen degradation in ALS/FTD patients could slow disease progression are also supported by our findings and could begin in a year.
