How gut bacteria influence Parkinson’s disease

The gut microbiome in Parkinson's: species level resolution and function

Dr. Silke Appel-Cresswell
University of British Columbia
Pilot Project Grant
Funded by Parkinson Society British Columbia
$50,000 over 1 year

Although Parkinson’s disease kills brain cells that affect our ability to move and to reason, the trillions of micro-organisms living in our gastrointestinal tracts may be important contributors to the illness.

At the University of British Columbia and with her colleagues at the University of Calgary, Dr. Silke Appel-Cresswell, a neurologist and associate professor, uses high-resolution screening tools to study the bacteria in the guts of people with Parkinson’s. This colony of bacteria, fungi and viruses is known as the microbiota.

Appel-Cresswell is pinpointing the particular strains of bacteria driving inflammation or allowing too many toxic proteins to move from the gut to the brain.

“From the evidence we have so far, it really seems that the microbiota in people with Parkinson’s are different from those in people who do not have Parkinson’s,” she says.

If particular strains of bacteria cause inflammation, for example, it could trigger the body to mount a too-aggressive immune response. This could also lead to the accumulation of the protein alpha-synuclein, damaging brain cells, including those that produce dopamine. Lack of dopamine-producing cells causes the stiffness, tremors and difficulty walking that characterize Parkinson’s disease.

“From the evidence we have so far, it really seems that the microbiota in people with Parkinson’s are different from those in people who do not have Parkinson’s.”

Certain strains of bacteria may also cause the gut wall to leak, enabling toxins to reach the blood and eventually the brain. A malfunctioning gut can also cause constipation, which leads to more inflammation and leaky gut.

“We’re working on all those pieces of the puzzle to prove what is happening,” Appel-Cresswell says.

Appel-Cresswell and her colleagues Dr. Davide Martino and Laura Sycuro in Calgary are analyzing fecal and blood samples donated from 300 people in Vancouver, and more than 100 others in Calgary.

If she can confirm mechanisms that link gut bacteria and Parkinson’s, her work could lead to treatment that attacks gut dysfunction, including constipation, early and aggressively to interrupt the vicious cycle. The research could also lead to recommended changes in diet and nutrition, including the use of probiotics. The role of nutrition in Parkinson’s is a closely linked research interest for Appel-Cresswell.

A screening tool could also be developed to identify those at higher risk of the disease.

“The Holy Grail would be to look at people who might be at risk, test their fecal microbiome, and if they show changes that point in the same direction, intervene early, when there are mostly symptoms at the level of the gut and the brain isn’t completely involved in the disease yet,” Appel-Cresswell says.

Appel-Cresswell is also motivated in her work by her father’s advanced-stage Alzheimer’s.

“It’s my personal mission to work on prevention of neurodegenerative diseases in general, especially with lifestyle interventions such as nutrition and exercise, given my family history and athletics background,” she says.

How your support made this research project possible

Appel-Cresswell’s new project builds on earlier research to study the fungal microbiome, a project Parkinson Canada supported. “That was one of the grants that then facilitated a whole lot more work,” she says.

“It’s really the seed funding, particularly with these pilot grants, that allows us to go way beyond that. It’s the necessary start to any of these projects.”

Seed or pilot grants allow researchers to leverage funding from other sources.

“You have to start somewhere, and that is the seed that is planted and has really grown into a whole program that is very interconnected and makes use of all these synergies between all these fields,” she says.

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