Oral Bacteria and Their Role in Parkinson's Disease via the Gut-Brain Axis

Recent research from Korean scientists has provided new insights into how bacteria originating in the mouth may influence the development of Parkinson's disease through the gut-brain connection. The study highlights that oral bacteria, once colonized in the gastrointestinal tract, can produce metabolites capable of reaching the brain and triggering neurodegenerative processes.

Led by Professor Ara Koh and doctoral candidate Hyunji Park at POSTECH, alongside collaborators from Sungkyunkwan University and Seoul National University, the team focused on the bacterial species Streptococcus mutans, commonly associated with dental caries. Their findings reveal that S. mutans produces specific enzymes, such as urocanate reductase (UrdA), leading to the generation of the metabolite imidazole propionate (ImP). Elevated levels of ImP were detected in the gut and bloodstream of Parkinson's patients.

Experimental studies using mouse models demonstrated that introducing S. mutans into the gut or engineering bacteria to express UrdA resulted in increased ImP levels in blood and brain tissues. These mice exhibited typical signs of Parkinson’s disease, including the loss of dopamine-producing neurons, heightened neuroinflammation, and the aggregation of alpha-synuclein protein. The pathogenic effects were linked to the activation of the mTORC1 signaling pathway. Notably, treatment with mTORC1 inhibitors mitigated neuronal loss, neuroinflammation, and behavioral symptoms.

The findings suggest that targeting the oral microbiome and its metabolic products could pave the way for new therapeutic strategies against Parkinson's disease. As Professor Koh summarized, "Our study provides a mechanistic understanding of how oral microbes in the gut influence brain health and may contribute to Parkinson's development," highlighting the potential for microbiome-focused interventions.

This groundbreaking work was published in Nature Communications and underscores the importance of oral health and the gut microbiota in neurological disorders, opening new avenues for research and therapy in neurodegenerative diseases.