In Parkinson’s disease (PD), certain dopamine-producing neurons in the brain die off, and aggregates of a molecule called α-synuclein form. Patients experience gradual and debilitating movement problems. Some studies have suggested that microbes in the gut are related to the development of PD. Research is now beginning to reveal some of the details of that connection. Reporting in Nature Communications, scientists have found unusually high levels of a microbe known as Streptococcus mutans and an enzyme it generates in the guts of Parkinson's patients. When researchers assessed the impact of the microbe and microbial enzyme in a mouse model, they saw symptoms of PD appear and get worse.
Streptococcus mutans is typically a part of the oral microbiome, and it’s known to cause cavities. But it seems to make it way to the gut sometimes, and may even be triggering PD once there.
S. mutans can make an enzyme called urocanate reductase (UrdA) and imidazole propionate (ImP), a metabolite. Both of these molecules were found at unusually high levels in the guts and blood of Parkinson’s patients. The study suggested that ImP can move into circulation to get to the brain, and once there, it influences the death of dopaminergic neurons.
A mouse model was used to test the impact of S. mutans, or E. coli that could produce UrdA. These mice subsequently carried unusually high levels of ImP in their blood and brains. They also displayed Parkinson’s-like symptoms, such as impaired movement; dopamine-producing neurons also died; and alpha-synuclein built up.
While the oral microbiome and gut-brain axis could be implicated in the development of Parkinson’s, they could also present new prevention or treatment options.
"Our study provides a mechanistic understanding of how oral microbes in the gut can influence the brain and contribute to the development of Parkinson's disease," said co-corresponding study author Professor Ara Koh of the Pohang University of Science and Technology. "It highlights the potential of targeting the gut microbiota as a therapeutic strategy, offering a new direction for Parkinson's treatment."
Sources: Pohang University of Science and Technology, Nature Communications
