A new study using a roundworm model of Parkinson’s disease has found that a probiotic bacteria can prevent, and in some cases reverse, the buildup of toxic proteins.
Poorly folded alpha-synuclein proteins in the brain are the hallmark of Parkinson’s disease.
Many experts believe that these toxic protein clusters lead to the progressive loss of brain cells that control movement.
But the science is unclear, and the underlying mechanisms that cause Parkinson’s disease remain elusive.
Without an effective way to prevent or cure Parkinson’s disease, treatment focuses primarily on symptom relief.
A recent line of research has studied a possible link with the intestinal microbiome, the thousands of billions of microbial species that inhabit our intestines.
Could changing a person’s gut microbiome be a way to change their risk of developing Parkinson’s disease or even serve as an effective treatment?
A group of scientists from the universities of Edinburgh and Dundee, both in the United Kingdom, have set out to investigate.
Maria Doitsidou, a member of the Center for Discovery Brain Sciences at the University of Edinburgh, is the lead author of the study, and the team’s research is featured in the journal Cell reports.
For their study, Doitsidou and his colleagues used a model of a nematode worm that scientists had genetically modified to express a human version of the alpha-synuclein protein.
These worms normally develop aggregates or clusters of alpha-synuclein on the first day of their adult life, 72 hours after hatching.
However, when the researchers fed worms, a diet containing a bacterial strain called probiotics Bacillus subtilis PXN21, they observed “an almost total absence of aggregates”, as they say in their article. The worms still produced the alpha-synuclein protein, but it did not aggregate in the same way.
In worms that have already developed protein aggregates, go to Subtilis removed aggregates from affected cells.
The team then followed a set of worms throughout their lives and compared a Subtilis diet with a conventional laboratory diet.
“The maximum number of aggregates reached in animals fed with Subtilis was much lower than that observed on the [standard] scheme, indicating that Subtilis does not simply delay the formation of aggregates, “explain the authors in the article.
“Subtilis PXN21 inhibits and reverses [alpha-synuclein] aggregation in a [roundworm] model, ”they note.
Is this effect specific to Subtilis PXN21, however? To answer this question, the team compared a number of different strains of the bacteria and found that they had similar effects.
To know how Subtilis is capable of preventing and eliminating alpha-synuclein aggregates, the team used an RNA sequencing analysis to compare the gene expression of animals receiving a standard diet with that of those receiving the probiotic.
This analysis revealed changes in the metabolism of sphingolipids. Sphingolipids are a type of fat molecule and they are important components of the structure of our cell membranes.
“Previous studies suggest that an imbalance of lipids, including ceramides and sphingolipid intermediates, may contribute to the pathology of [Parkinson’s disease]“, Comment the authors in the article.
However, changes in the metabolism of sphingolipids were not the only pathways identified by the researchers.
They also saw that Subtilis was able to protect older animals from alpha-synuclein aggregation both by the formation of complex structures called biofilms and by the production of nitric oxide. In addition, the team found changes in food restriction and insulin-like signaling pathways.
It is important to note that when the team changed the animals that had received a diet for the first time Subtilis diet, their motor skills improved.
“The results are an opportunity to study how the modification of the bacteria that make up our gut microbiome affects Parkinson’s disease. The next steps are to confirm these results in mice, followed by accelerated clinical trials since the probiotic we tested is already commercially available. ”