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"... Korean researchers have uncovered compelling evidence that oral bacteria, once colonized in the gut, can affect neurons in the brain and potentially trigger Parkinson's disease. ...
They have identified the mechanism by which metabolites produced by oral bacteria in the gut may trigger the development of Parkinson's disease. ...
Although previous studies suggested that the gut microbiota of individuals with Parkinson's differs from that of healthy individuals, the specific microbes and metabolites have remained unclear.
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. ..."
From the abstract:
"Parkinson’s disease (PD) is characterized by the selective degeneration of midbrain dopaminergic neurons and aggregation of α-synuclein. Emerging evidence implicates the gut microbiome in PD, with microbial metabolites proposed as potential pathological mediators.
However, the specific microbes and metabolites involved, and whether gut-derived metabolites can reach the brain to directly induce neurodegeneration, remain unclear.
Here we show that elevated levels of Streptococcus mutans (S. mutans) and its enzyme urocanate reductase (UrdA), which produces imidazole propionate (ImP), in the gut microbiome of patients with PD, along with increased plasma ImP. Colonization of mice with S. mutans harboring UrdA or Escherichia coli expressing UrdA from S. mutans increases systemic and brain ImP levels, inducing PD-like symptoms including dopaminergic neuronal loss, astrogliosis, microgliosis, and motor impairment.
Additionally, S. mutans exacerbates α-synuclein pathology in a mouse model. ImP administration alone recapitulates key PD features, supporting the UrdA–ImP axis as a microbial driver of PD pathology.
Mechanistically, mTORC1 activation is crucial for both S. mutans- and ImP-induced PD pathology. Together, these findings identify microbial ImP, produced via UrdA, as a direct pathological mediator of the gut-brain axis in PD."
Fig. 1: Increased urdA enzyme abundance in the gut microbiome of patients with Parkinson’s disease (PD) and PD key pathologies induced by gut-colonization of imidazole propionate (ImP)-producing Streptococcus mutans (S. mutans).
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