Researchers in South Korea report evidence that an oral bacterium best known for causing tooth decay can colonize the gut and generate a metabolite that reaches the brain and triggers Parkinson’s-like pathology in mouse experiments. The work, published in Nature Communications, adds to growing evidence that gut microbes and their byproducts may influence neurodegenerative disease processes.
A research team led by Professor Ara Koh and doctoral candidate Hyunji Park at Pohang University of Science and Technology (POSTECH) reports a possible biological route connecting oral bacteria to Parkinson’s disease (PD), based on analyses of patient microbiome data and a series of mouse experiments.
In the study, the researchers found higher levels of Streptococcus mutans—a common mouth bacterium associated with dental caries—in the gut microbiomes of people with Parkinson’s disease. They also reported elevated levels of a bacterial enzyme, urocanate reductase (UrdA), and its metabolic product, imidazole propionate (ImP), alongside increased ImP in patients’ blood.
The researchers’ experiments suggest this UrdA–ImP pathway could contribute to disease-related brain changes. In mouse studies, colonizing the gut with S. mutans carrying UrdA, or using genetically modified Escherichia coli to express UrdA, increased ImP levels in the animals’ circulation and brain tissue. The animals developed Parkinson’s-like features reported by the authors, including loss of dopamine-producing neurons, inflammation in the brain, movement impairments, and increased accumulation of α-synuclein, a protein closely linked to Parkinson’s pathology.
The paper further reports that the effects depended on activation of the mTORC1 signaling pathway. When mice were treated with a drug that inhibits mTORC1, the team observed reductions in neuroinflammation, dopaminergic neuron loss, α-synuclein buildup and motor problems.
“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,” Koh said.
Parkinson’s disease is a common neurodegenerative disorder associated with tremor, muscle rigidity and slowed movement. The ScienceDaily summary of the work, citing POSTECH, describes PD as affecting about 1% to 2% of people worldwide over age 65.
The researchers said the work helps narrow earlier observations that the gut microbiome differs in people with Parkinson’s by identifying a specific oral microbe and metabolite pathway that, in their mouse models, can drive PD-like pathology.
According to the Nature Communications paper, the research was funded in part by the Samsung Research Funding & Incubation Center of Samsung Electronics and grants supported by South Korea’s Ministry of Science and ICT, among other programs.
