Oral bacteria linked to Parkinson’s via the gut-brain axis
Finding highlights the potential of targeting the gut microbiota as a therapeutic strategy.
Oral bacteria in the gut can trigger Parkinson’s disease through metabolites that penetrate the brain, researchers have found.
Parkinson’s disease affects 1-2% of the global population over the age of 65, making it one of the most common age-related brain diseases. Although previous studies have suggested that the gut microbiota of individuals with Parkinson’s differs from that of healthy individuals, the specific microbes and metabolites have remained unclear.
Researchers at Pohang University of Science and Technology and Sungkyunkwan University School of Medicine in South Korea have identified the mechanism by which metabolites produced by oral bacteria in the gut may trigger the development of Parkinson’s.
They found an increased abundance of Streptococcus mutans – a well-known oral bacterium that causes dental caries – in the gut microbiome of Parkinson’s patients.
More importantly, 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. ImP appeared capable of entering systemic circulation, reaching the brain, and contributing to the loss of dopaminergic neurons.
Using mouse models, the researchers introduced S. mutans into the gut or engineered E. coli to express UrdA. As a result, 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.
Further experiments demonstrated that these effects depend on the activation of the signaling protein complex mTORC1. Treating mice with an mTORC1 inhibitor significantly reduced neuroinflammation, neuronal loss, and alpha-synuclein aggregation, and motor dysfunction. This suggests that targeting the oral–gut microbiome and its metabolites may offer new therapeutic strategies for Parkinson’s disease.
“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,” said Professor Ara Koh, one of the research team leaders. “It highlights the potential of targeting the gut microbiota as a therapeutic strategy, offering a new direction for Parkinson’s treatment.”
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