Over the past few years, several research groups have drawn links between the gut microbiome and central nervous system disorders, especially Parkinson’s disease. Now, scientists at the universities of Edinburgh and Dundee are going a step further and investigating a treatment strategy that capitalizes on microbes in the gut that may protect against the neurodegenerative disease.
The researchers started with roundworms engineered to produce the human version of alpha-synuclein protein, which is a major culprit in Parkinson’s. In people, alpha-synuclein misfolds and forms toxic clumps in the brain, leading to the death of nerve cells that produce dopamine. That, in turn, causes the tremors, movement difficulties and other symptoms typical of the disease.
The team fed the worms various over-the-counter probiotics and discovered that one in particular—Bacillus subtilis—cleared some alpha-synuclein clumps and improved motor symptoms. They published the findings in the journal Cell Reports.
This doesn’t mean everyone should go to the drugstore to buy probiotics, the researchers warn—the finding needs to be confirmed in mice and then in large-scale clinical trials. But they believe it does bolster previous discoveries linking gut microbes to Parkinson’s.
"The results provide an opportunity to investigate how changing the bacteria that make up our gut microbiome affects Parkinson's,” said lead author Maria Doitsidou, Ph.D., of the Centre for Discovery Brain Sciences at the University of Edinburgh, in a statement.
Doitsidou and colleagues discovered that B. subtilis works by changing how enzymes process specific fats known as sphingolipids. The bacterium produces chemicals that spark the change, which in turn prevents alpha-synuclein protein from forming clumps.
Several research groups have turned to the gut microbiome in search of new ideas for treating Parkinson’s. Last June, Johns Hopkins University School of Medicine researchers published research showing that in mice, misfolded alpha-synuclein protein can travel from the gut to the brain. And in 2018, a team led by Michigan-based Van Andel Research Institute studied two large patient registries and found that people who have their appendixes removed lower their chances of getting Parkinson’s by up to 25%—a phenomenon they suspected was related to their discovery of alpha-synuclein clumps in appendix tissue.
There has also been entrepreneurship in biopharma centered around exploiting the gut-brain connection in Parkinson’s. In 2016, California Institute of Technology scientists showed in mouse models that some gut bacteria promote Parkinson’s progression, leading them to launch Axial Biotherapeutics to pursue microbiome-aimed treatments for the disease and other central nervous system disorders. Last February, the company raised $25 million in a series B round that was led by Seventure Partners’ microbiome-focused Health for Life Capital fund. Enterin has also snapped up capital to advance its lead drug targeting alpha-synuclein.
The new research centered around the probiotic B. subtilis was partially funded by Parkinson’s UK, which hopes that clinical trials stemming from the research will be fast-tracked. “Studies that identify bacteria that are beneficial in Parkinson's have the potential to not only improve symptoms but could even protect people from developing the condition in the first place,” said the organization’s research manager, Beckie Port, Ph.D., in the statement.