Mouth Bacteria's Role in Parkinson's Disease Development

Researchers in South Korea have found strong evidence that bacteria from the mouth can move into the gut and influence brain cells, potentially playing a role in the development of Parkinson’s disease. The study was carried out by a collaborative team led by Professor Ara Koh and doctoral candidate Hyunji Park from POSTECH’s Department of Life Sciences. The team identified a biological process showing how substances produced by oral bacteria in the gut may help set Parkinson’s disease in motion. Their findings were published in Nature Communications. The researchers discovered higher levels of Streptococcus mutans in the gut microbiomes of people with Parkinson’s. This bacterium produces an enzyme called urocanate reductase (UrdA) along with a metabolic byproduct known as imidazole propionate (ImP). Both substances were found at increased levels in the gut and bloodstream of patients. Evidence suggested that ImP can travel through the body, reach the brain, and contribute to the loss of dopamine-producing neurons. To better understand this process, the team conducted experiments in mice. They either introduced S. mutans directly into the animals’ guts or genetically modified E. coli to produce UrdA. In both cases, ImP levels rose in the blood and brain tissue. The mice developed key features associated with Parkinson’s disease, including damage to dopaminergic neurons, increased brain inflammation, movement problems, and greater build-up of alpha-synuclein, a protein closely tied to disease progression. Additional experiments showed that these harmful effects depended on activation of a signaling protein complex called mTORC1. When mice were treated with a drug that inhibits mTORC1, researchers saw a clear reduction in brain inflammation, neuron loss, alpha-synuclein accumulation, and motor problems. These results suggest that targeting the oral-gut microbiome and the compounds it produces could open new paths for treating Parkinson’s disease.