Parkinson's May Be Started and Fueled By Gut Bacteria

Researchers have discovered that a common bacterium, Streptococcus mutans, may contribute to Parkinson's disease by producing a molecule called imidazole propionate, which can reach the brain and cause inflammation, neuron loss, and typical motor symptoms of the disease. The study reinforces the role of the intestine in the development of Parkinson's and points to new avenues for prevention and treatment.

Parkinson's disease is the second most common neurodegenerative condition in the world, second only to Alzheimer's. It is estimated that more than 10 million people live with Parkinson's worldwide, and this number is expected to increase as the population ages.

This disease is primarily characterized by the progressive death of dopamine-producing neurons in a region of the brain called the substantia nigra. Dopamine is an essential neurotransmitter for controlling movement, and the loss of this system generates symptoms such as tremors, muscle stiffness, and slowness of movement.

Although genetic factors may contribute, most cases are considered idiopathic, meaning they have no clearly defined cause. This suggests that environmental factors, such as exposure to pesticides, heavy metals, viruses, and even dietary habits, play an important role.

In recent years, scientists' attention has turned to the gut and its microbiome, the community of trillions of bacteria that live in the digestive tract. Studies show that people with Parkinson's have a different gut microbiota composition than healthy individuals.

In animal experiments, when the microbiota of people with Parkinson's is transplanted into mice, the mice develop symptoms similar to those of the disease. This suggests that gut microorganisms and their molecules may play a role in the development of the condition.

The connection between the gut and brain, called the gut-brain axis, may allow substances produced by bacteria in the gut to reach the central nervous system and influence neurons.

Among the most studied hypotheses is the possibility that microbial metabolites, small molecules produced by bacteria, can cross biological barriers and reach the brain. An important class of these molecules are short-chain fatty acids, derived from the fermentation of dietary fiber by gut bacteria.

Bacteria Streptococcus mutans

In some experiments, they were able to intensify inflammatory processes in the brain, further damaging dopaminergic neurons. Furthermore, Parkinson's patients have reduced levels of bacteria that produce protective substances, such as butyrate, which reinforces the idea of ​​a harmful microbial imbalance.

To investigate this phenomenon, a large study analyzed the feces of nearly 500 people with Parkinson's and more than 200 healthy elderly individuals. Using modern genomic sequencing techniques, the researchers mapped the microbial composition in detail and identified significant differences between the two groups.

One of the most striking findings was the increased presence of the bacterium Streptococcus mutans, best known for causing tooth decay but which can also colonize the intestine. This bacterium produces an enzyme called urocanate reductase (UrdA), which transforms a natural substance in the body called urocanate into another molecule called imidazole propionate (ImP).

In the experimental part of the study, scientists colonized mice with Streptococcus mutans or Escherichia coli modified to carry the same enzyme. The result was an increase in imidazole propionate levels in both the blood and brains of these animals.

This increase was accompanied by the appearance of Parkinson's-like symptoms: progressive loss of dopaminergic neurons, brain inflammation, and motor difficulties.

This image shows the effects of E. coli bacteria modified to produce the UrdA enzyme compared to the normal version of the bacteria (control E. coli). On the left, we see images of mouse brains. Animals exposed to the bacteria with UrdA lost significantly more dopaminergic neurons (cells that produce dopamine) in a region called the substantia nigra, which is precisely the area most affected by Parkinson's disease. On the right, the graphs confirm this loss: there are fewer dopaminergic neurons (TH and Nissl) and a lower density of dopamine fibers in the animals with the modified bacteria, while the total number of neurons in another region remained unchanged.

When imidazole propionate was administered alone, without the bacteria, the animals also developed the main features of the disease. This confirmed that the molecule alone is capable of causing changes consistent with Parkinson's.

The study also showed that this molecule activates a cellular signaling pathway called mTORC1, already known to be involved in aging and neurodegeneration. Thus, the research suggests that the production of imidazole propionate by gut bacteria may be a direct link between the microbiome and the brain degeneration observed in Parkinson's.

These results not only reinforce the role of the gut in the disease but also pave the way for new therapeutic strategies. Interventions that modify the microbiome, reduce the presence of bacteria such as Streptococcus mutans, or neutralize the effects of imidazole propionate may, in the future, become important tools for preventing or treating Parkinson's.

The graphical abstract illustrates that the UrdA-ImP axis is elevated in the gut microbiome of patients with Parkinson's disease (PD). Using murine models, we demonstrate that this causally contributes to PD pathology through mTORC1 activation. These findings identify UrdA as a potential gut microbiome-based therapeutic target for gut-brain axis disorders such as PD. Created in BioRender. Kim, J. (https://BioRender.com/vg7s2sy).

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Gut microbial production of imidazole propionate drives Parkinson’s pathologies

Hyunji Park, Jiwon Cheon, Hyojung Kim, Jihye kim, Jihyun Kim, Jeong-Yong Shin, Hyojin Kim, Gaeun Ryu, In Young Chung, Ji Hun Kim, Doeun Kim, Zhidong Zhang, Hao Wu, Katharina R. Beck, Fredrik Bäckhed, Han-Joon Kim, Yunjong Lee, and Ara Koh 

Nature Communications. volume 16, Article number: 8216 (2025). 

https://doi.org/10.1038/s41467-025-63473-4

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.