Bacterial Sugars in the Gut May Play a Role in Neurodegenerative Diseases
New research indicates that sugars produced by gut bacteria might be a hidden factor in two severe neurodegenerative diseases, namely amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).
Both conditions are interconnected and involve the degeneration of neurons. This neuronal death leads to muscle impairment in ALS, which is ultimately fatal, and significant behavioral and language changes in FTD, sometimes affecting movement as well.
Currently, the origins of these diseases remain unclear. A research team from Case Western Reserve University aimed to explore whether gut bacteria could influence the onset of these conditions, building on previous studies linking gut health to ALS.
Using mouse models, the researchers discovered a specific kind of glycogen produced by gut bacteria that appears to induce brain inflammation and neuron damage.
According to Aaron Burberry, an assistant professor at Case Western Reserve University, “We found that harmful gut bacteria create inflammatory forms of glycogen – a sugar that sparks immune responses capable of harming the brain.” This discovery is a stepping stone towards developing potential treatments.
In some cases, ALS and FTD are associated with variations of the C9ORF72 gene, although not everyone with this genetic alteration develops the diseases. The primary goal of the study was to identify other contributing factors in individuals who carry the gene variant.
The researchers meticulously engineered mice lacking the C9ORF72 gene to simulate the genetic variation in humans. Subsequently, they tested various gut bacteria mixes to observe immune system responses.
This process led them to glycan production and specifically the Parabacteroides merdae strain, which, when introduced to mice without gut bacteria, caused inflammation and compromised the blood-brain barrier.
Analysis of human stool samples revealed elevated inflammatory glycogen levels in 15 out of 22 ALS patients and one FTD patient, contrasting with only four out of 12 healthy controls.
The researchers hypothesize that when the immune system detects potentially harmful glycogen, it overreacts, which may adversely affect brain health. Notably, the C9ORF72 protein seems to modulate glycogen levels, which sheds light on the risks associated with the gene variation.
As outlined in their published findings, the team noted that the presence of microbes producing inflammatory glycogen is prevalent in the guts of ALS patients and suggest this may be an important environmental factor interacting with genetic predispositions.
One encouraging outcome from the study was that when affected mice received an enzyme called alpha-amylase to break down glycogen, inflammation decreased and lifespans improved, although motor performance did not show improvement.
This suggests a potential path for future treatments that might target gut health rather than directly addressing brain issues, although this remains in early stages of investigation.
There’s growing awareness about the connection between gut health and brain function, and this research adds to that body of knowledge.
The researchers aim to further their studies by examining human participants and different types of glycogen-producing bacteria.
Moving forward, Burberry mentioned the importance of understanding when and why harmful microbial glycogen is produced, noting that larger studies on gut microbiomes of ALS/FTD patients before and after onset will soon be pursued. Clinical trials aimed at exploring whether glycogen reduction could slow disease progression could begin within the year.
The research findings are available in Cell Reports.
