KEY POINTS:
- Scientists at POSTECH and Sungkyunkwan University found that Streptococcus mutans, an oral bacterium known for causing cavities, can migrate to the gut and potentially trigger Parkinson’s disease, according to Nature Communications on September 5
- The bacteria produces a metabolite called imidazole propionate (ImP) that can cross the blood-brain barrier and cause dopaminergic neuron loss, neuroinflammation, and motor impairments in mice, as reported in the Nature Communications study
- Patients with Parkinson’s disease showed significantly elevated levels of S. mutans in their gut microbiome and higher blood ImP levels compared to healthy controls, according to the research published in Nature Communications
Scientists have discovered compelling evidence that oral bacteria, once colonized in the gut, can affect neurons in the brain and potentially trigger Parkinson’s disease, according to research published in Nature Communications on September 5.
The joint research team, led by Professor Ara Koh and doctoral candidate Hyunji Park of POSTECH’s Department of Life Sciences, together with Professor Yunjong Lee and doctoral candidate Jiwon Cheon of Sungkyunkwan University School of Medicine, collaborated with Professor Han-Joon Kim of Seoul National University College of Medicine, as reported by NeuroscienceNews.
The Oral-Gut-Brain Connection
The researchers found an increased abundance of Streptococcus mutans—a well-known oral bacterium that causes dental caries—in the gut microbiome of Parkinson’s patients, according to the Nature Communications study. S. mutans produces the enzyme urocanate reductase (UrdA) and its metabolite imidazole propionate (ImP), both of which were present at elevated levels in the gut and blood of patients, the study reported.
“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,” Professor Ara Koh told NeuroscienceNews. “It highlights the potential of targeting the gut microbiota as a therapeutic strategy, offering a new direction for Parkinson’s treatment.”
Evidence from Multiple Studies
The findings align with previous research on gut microbiome changes in Parkinson’s disease. Nature Communications reported in November 2022 that in a large-scale study of 490 Parkinson’s patients and 234 healthy controls, Streptococcus mutans was elevated by sixfold in patients with the disease.
Communications Medicine reported on October 23, 2024, that three S. mutans OTUs (operational taxonomic units) were particularly elevated in Parkinson’s disease cases in their analysis of 445 patients versus 221 controls.
The UAB News reported that at one end of the spectrum, Streptococcus mutans showed a sixfold increase in Parkinson’s patients, according to research published in Nature Communications.
How the Bacteria Triggers Disease
Using mouse models, the researchers introduced S. mutans into the gut or engineered E. coli to express UrdA, as reported in the Nature Communications study. The mice showed elevated ImP levels in blood and brain tissue, along with the hallmark features of Parkinson’s symptoms: loss of dopaminergic neurons, heightened neuroinflammation, impaired motor function, and increased aggregation of alpha-synuclein, a protein central to disease progression, according to the study.
The Nature Communications research stated that ImP appeared capable of entering systemic circulation, reaching the brain, and contributing to the loss of dopaminergic neurons. The study found that chronic ImP administration to mice activated neurodegenerative pathways, worsened Parkinson’s-like neuropathology, and increased blood-brain barrier permeability.
Mechanism of Action
Further experiments demonstrated that these effects depend on the activation of the signaling protein complex mTORC1, according to the Nature Communications study. The research reported that treating mice with an mTORC1 inhibitor significantly reduced neuroinflammation, neuronal loss, alpha-synuclein aggregation, and motor dysfunction.
Parkinson’s disease affects approximately 1-2% of the global population over the age of 65, making it one of the most common age-related brain diseases, as stated in the Nature Communications study published on September 5.
Implications Beyond Parkinson’s
The bacterial metabolite ImP has implications beyond Parkinson’s disease. PMC reported that ImP has been previously associated with several Alzheimer’s disease comorbidities, such as type 2 diabetes and cardiovascular disease.
Nature reported on July 16, 2025, that imidazole propionate produced by gut microbiota is associated with atherosclerosis in mouse models and in humans, and causes the development of atherosclerosis through activation of the imidazoline-1 receptor in myeloid cells.
Nature Communications reported on December 21, 2020, that subjects with prediabetes and diabetes have elevated serum imidazole propionate levels, and that ImP levels were increased in subjects with low bacterial gene richness and Bacteroides 2 enterotype.
Future Treatment Possibilities
The research opens new avenues for treatment. Nature reported on April 24, 2025, about trials testing fecal microbiota transplantation for Parkinson’s disease, with researchers at Ghent University Hospital in Belgium observing improvements in motor function scores.
The Samsung Research Funding & Incubation Center of Samsung Electronics, the Mid-Career Researcher Program of the Ministry of Science and ICT, the Microbiome Core Research Support Center, and the Biomedical Technology Development Program supported the research, according to NeuroscienceNews.
