Summary: Scientists have discovered a direct link between oral bacteria and Parkinson’s disease. They discovered that Streptococcus mutans, which is known to cause cavities, can colonize the intestines and release metabolites that reach the brain.
These metabolites cause neuronal damage, neuroinflammation, and motor impairment similar to Parkinson’s disease. The results suggest that targeting the oral gut microbiome could lead to new strategies for disease prevention or treatment.
Key facts
- Oral–Gut–Brain Link: Streptococcus mutans can migrate from the mouth to the intestines and invade the brain.
- Toxic metabolite: The metabolite IMP damages dopaminergic neurons and promotes Parkinson’s disease.
- Treatment potential: Blocking mTORC1 signaling reduced neuroinflammation and motor symptoms in mice.
Source: POSTECH
Now there’s another reason to brush your teeth thoroughly every day. Korean researchers have found compelling evidence that oral bacteria, once colonized in the gut, can affect brain neurons and potentially cause Parkinson’s disease.
The joint research team, led by Professor Ara Koh and PhD student Hyunji Park from POSTECH’s Department of Life Sciences, along with Professor Yunjong Lee and PhD student Jeon Cheon from Sungkyunkwan University College of Medicine, collaborated with Professor Han Jun Kim from Seoul National University College of Medicine.
Researchers have uncovered a potential mechanism linking oral bacteria to the development of Parkinson’s disease. Specifically, they identified how certain metabolites produced by oral bacteria, once they reach the gut, may trigger processes that contribute to this debilitating neurological condition. This breakthrough adds to a growing body of evidence highlighting the importance of the gut-brain connection in neurodegenerative disorders. By tracing the influence of microbial activity from the mouth to the gastrointestinal system, scientists are beginning to understand how seemingly unrelated biological systems can interact in complex ways to influence brain health.
The findings of this study were published online in Nature Communications on September 5, marking a significant advancement in the field of Parkinson’s research. The research provides a more detailed understanding of the biological pathways through which microbial metabolites may influence inflammation, neural function, or other cellular mechanisms involved in the early stages of Parkinson’s disease. It also opens up new avenues for preventative and therapeutic interventions, potentially focusing on oral health, microbiome management, or metabolic modulation to reduce the risk of disease onset.
Parkinson’s disease is a progressive and serious neurological disorder that primarily affects motor function. It is characterized by symptoms such as tremors, muscle rigidity, and a pronounced slowness of movement. The disease results from the gradual degeneration of dopamine-producing neurons in the brain, though the exact causes have remained unclear for many patients. Affecting approximately 1–2% of the global population over the age of 65, Parkinson’s ranks among the most common age-related brain diseases. This new research underscores the complexity of its origins and the potential role of seemingly distant physiological systems—like the gut and oral microbiome—in influencing brain health and disease development.
Previous studies have already shown that the gut flora of people with Parkinson’s disease is different from that of healthy individuals. However, it is unclear which specific microbes and metabolites these are.
They discovered increased concentrations of Streptococcus mutans (a well-known oral bacterium that causes tooth decay) in the gut microbiome of Parkinson’s disease patients.
More importantly, S. mutans produces the enzyme urocanate reductase (UrdA) and its metabolite, imidazole propionate (ImP). Both are present in high concentrations in the intestines and blood of patients. IMP was shown to be able to enter the systemic circulation, reach the brain, and contribute to the loss of dopaminergic neurons.
Using mouse models, the researchers introduced S. mutans into the intestines or genetically modified E. coli to express Urdu A. As a result, the mice exhibited elevated IMP levels in the blood and brain tissue, along with symptoms of Parkinson’s disease: loss of dopaminergic neurons, increased neuroinflammation, impaired motor function, and increased accumulation of alpha-synuclein, a key protein for disease progression.
Follow-up experiments demonstrated that these effects depended on activation of the mTORC1 signaling protein complex. Treating mice with an mTORC1 inhibitor significantly reduced neuroinflammation, neuronal damage, alpha-synuclein aggregation, and motor impairment.
This suggests that targeting the oral gut microbiome and its metabolites may provide new therapeutic strategies for Parkinson’s disease.
“Our research provides a mechanistic insight into how oral microbes in the gut may affect the brain and contribute to the development of Parkinson’s disease,” said Professor Ara Koh, emphasizing the significance of their findings in uncovering the complex biological pathways that link microbial activity in the gastrointestinal tract to neurological function. By demonstrating how metabolites produced by oral bacteria can travel to the gut and potentially trigger processes involved in neurodegeneration, the study highlights a previously underexplored connection between the mouth, the gut, and the brain. This insight not only deepens scientific understanding of Parkinson’s disease but also opens the door to novel preventative strategies and therapeutic approaches that could target microbial imbalances or metabolic disruptions at early stages of disease progression.
“This highlights the potential of targeting the gut microbiota as a therapeutic strategy, providing a new direction for the treatment of Parkinson’s disease.”
Funding: This research was supported by the Samsung Electronics Research Funding and Incubation Center, the Ministry of Science and ICT’s Mid-Career Researcher Program, the Central Microbiome Research Support Center, and the Biomedical Technology Development Program.
About this Parkinsons’s disease research news
Author: Yung-Eui Kang
Source: POSTECH
Contact: Yung-Eui Kang – POSTECH
Image: The image is credited to StackZone Neuro
Original Research: Open access.
“Gut microbial production of imidazole propionate drives Parkinson’s pathologies” by Ara Koh et al. Nature Communications
Abstract
Production of imidazole propionate by gut microbes causes Parkinson’s disease.
Parkinson’s disease (PD) is characterized by selective degeneration of dopaminergic neurons in the midbrain and accumulation of α-synuclein. There is increasing evidence that the gut microbiome plays a role in PD, and microbial metabolites are being proposed as potential pathological mediators.
However, it is still unclear which specific microbes and metabolites are involved, and also whether metabolites from the gut can reach the brain and directly cause neurodegeneration.
Here we show that elevated levels of Streptococcus mutans (S. mutans) and its enzyme urocanate reductase (UrdA), which produces imidazole propionate (ImP), are present in the gut microbiome of PD patients, along with elevated plasma ImP.
Colonization of mice with S. mutans containing urdA or Escherichia coli expressing UrdA from S. mutans increases systemic and brain levels of IMP, which induces PD-like symptoms including dopaminergic neuronal loss, astrogliosis, microgliosis, and motor dysfunction.
Furthermore, S. mutans exacerbates α-synuclein pathology in a mouse model. ImP administration alone reproduces key features of PD, supporting the UrdA-ImP axis as a microbial driver of PD pathology. Mechanistically, mTORC1 activation is critical for both S. mutans- and ImP-induced PD pathology.
Together, these results identify microbial ImP, produced by UrdA, as a direct pathological mediator of the brain-gut connection in PD.
