Pictured (left to right) are Dr. Seti Boroomand, lead author Mihai Cirstea, co-author Kristen Sundvick, co-author Ella Golz, team lead Dr. Silke Cresswell, and research coordinator Adam Yu.
Over the past decade, researchers have been studying the human microbiome—an array of microorganisms including bacteria, parasites, viruses, and fungi—to determine how it might be involved in disease. When it comes to Parkinson’s Disease (PD), most research has focused on defining the PD microbiome and attempting to link these microorganisms to neurological systems.
A study published this week in the journal Movement Disorders took a new approach in looking at the PD microbiome. The team—led by DMCBH researcher and neurologist Dr. Silke Cresswell and microbiologist in Michael Smith Laboratories Dr. Brett Finlay—looked at how microbiota composition relates to gastrointestinal function in Parkinson’s.
“It’s been known for a long time that people living with Parkinson’s have gastrointestinal comorbidities—constipation being the most well understood one— and many of these issues appear long before a person is diagnosed and can have a significant impact on their lives,” says Mihai Cirstea, PhD student and lead author on the study. “But most other studies treat gut comorbidities such as constipation as a confounder that they adjust for when they look at the microbiome. We know this is part of the disease rather than just a covariant, so we decided gastrointestinal issues were inherently worth looking at.”
The team focused on constipation and transit time (how quickly or slowly food moves through the intestines), analyzing gut bacteria in 197 Parkinson’s patients and 103 controls. They found many differences in the microbiome between controls and PD patients, with several bacteria in PD patients positively associated with constipation. They also found that many bacteria known to be important in promoting a healthy gut were less prevalent in PD patients than in controls.
The team took their study one step further and looked at bacterial metabolism to see if this would provide any clues to the mechanisms by which the microbiome plays a role in gut function. They compared fecal microbiome composition to metabolites in the blood and found that two bacterial metabolites in particular—p-cresol and phenylacetylglutamine—were elevated in PD patients compared to controls. These same metabolites were also associated with the bacteria they found to be elevated in PD patients and were both correlated with firmer stools and constipation severity.
“This is one of the first studies that focused on the gut rather than looking at PD and the microbiome in the context of motor symptoms or cognition,” says Cirstea. “We really were looking back to where these microorganims live and seeing how they were situated with the conditions of the gut.”
The challenge with any microbiome study is that it’s hard to infer causation—is it the microbiome that’s contributing to PD, or is it PD that’s changing the microbiome? This, says Cirstea, is the toughest question to answer. However, more studies like this one will help guide future questions and provide new avenues to explore. Gastrointestinal issues such as constipation can happen many years before typical Parkinson’s onset, so it’s possible that in the future, microbiome-based interventions could help to manage these symptoms.
The study is set to continue, with data from the 300 participants being collected for five years. This way, the team will have baseline data to use for comparison in the long-term.
“Perhaps there is a bacterium or metabolite that’s elevated in year three compared to year one, and maybe that person’s disease has progressed, or their gastrointestinal symptoms have gotten worse,” says Cirstea. “Then we can compare and hypothesize that there might be an actual mechanistic connection between these disease changes and the microbiome.”