Since 2014, researchers such as Dr. Silke Appel-Cresswell have been studying the gut as a key area in potentially unravelling the mysteries of what causes Parkinson’s to develop. 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.

Dr. Appel-Cresswell recently published a study with negative findings and is embarking on a new project to investigate further: both having received funding from the Parkinson Canada Research Program.

The bacterial gut microbiome is strongly associated with Parkinson’s as shown by numerous studies including by Dr. Appel-Cresswell. However, no studies had previously investigated the role of fungi in the gut. In this novel study published in the Journal of Parkinson’s Disease, and partly funded by Parkinson Canada Dr. Appel-Cresswell and a team of investigators at the University of British Columbia examined whether the fungal constituents of the gut microbiome are associated with Parkinson’s.

In summary, their research found that gut fungi are not a contributing factor, thereby refuting the need for any potential anti-fungal treatments of the gut in Parkinson’s patients. Parkinson Canada (along with other funders) supported this negative finding, and we are now investing in a follow up study to further investigate the role of the gut in Parkinson’s.

In this first study, analysis determined that the fungal microbiome in Parkinson’s did not essentially differ from matched controls. There were no strong associations between gut fungi and Parkinson’s symptoms.

The Parkinson Canada Research Program funds novel ideas like this to help discover the next big breakthrough in Parkinson’s research and help understand what may not be a contributing factor. Both elements are an important part of discovery. Additionally, negative study results ensure that future research funds aren’t wasted on exploring something that has already been disproven.

“The data are an important piece in the puzzle of understanding the overall role of the gut microbiome in Parkinson’s,” Dr. Appel-Cresswell said. “Parkinson’s patients can rest assured that gut fungal overgrowth, or dysbiosis, is likely not a contributing factor to any of their Parkinson’s symptoms, both motor and non-motor.”

“The gut microbiome continues to be an exciting field of research where we are just at the beginning of unraveling potential mechanisms.”

That’s why she’s continuing to investigate the role of the gut in Parkinson’s. Now, Dr. Appel-Cresswell and her collaborators want to pinpoint the particular strains of bacteria that are likely driving inflammation or allowing too many toxic proteins to move from the gut to the brain.

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.

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 understand what is happening,” Appel-Cresswell said.

Dr. 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 they 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 tailored probiotics, or a screening tool could be developed to identify those at higher risk of the disease.

Parkinson Canada’s Director of Research Program and Partnerships, Julie Wysocki, recognizes the importance of studies like this. “It is vital that researchers investigate areas that may contribute to the onset of the disease,” she said, while acknowledging the importance of publishing this specific set of results.

“It is important that all findings, even negative ones be shared and published in order to eliminate duplication in research so that researchers can continue to explore new areas which may lead to breakthroughs.”

To learn more about the specific goals of Dr. Appel-Cresswell’s grant funded by Parkinson Society British Columbia through the Parkinson Canada Research Program and 19 other projects investigating equally important questions, visit the new research portal on Parkinson.ca featuring this year’s funding cycle and much more.

Editor’s Note:

Your support makes research like this possible. Dr. 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.

Donate to fund more research projects.

This article references an original post that appears on sciencedaily.com from IOS Press.

“Study suggests that gut fungi are not associated with Parkinson’s disease: Although the bacterial microbiome is strongly connected to PD and gut dysfunction is nearly universal in this disease.” ScienceDaily. ScienceDaily, 21 January 2021.