Could Parkinson’s disease start in the gut?

“Parkinson’s disease ‘may start in gut” BBC News reports. New research involving mice suggests that bacteria in the gut may lead to a greater decline in motor function in patients with Parkinson’s disease.

The study involved a mouse model of Parkinson’s disease. The researchers gave some mice gut bacteria from people with Parkinson’s disease, some with gut bacteria from healthy individuals, and some mice were not given any bacteria.

They found that gut bacteria seemed necessary to trigger Parkinson’s like symptoms. There was greater decrease in motor function in mice infected with gut bacteria compared with those who remained germ-free, with the greatest decline seen in mice given bacteria from people with Parkinson’s.

The researchers suggest that the presence of gut bacteria may cause the build-up of proteins called alpha synuclein, which is found in patients with Parkinson’s disease.

The study doesn’t prove that Parkinson’s is essentially a gut disorder and could potentially be treated or prevented with antibiotics or probiotics. And, humans aren’t identical to mice, so the study findings may not apply to people.

The study arguably raises more questions than answers. But it could pave the way for further studies in humans, with the hope of finding potential new treatments for Parkinson’s.

Where did the story come from?

The study was carried out by researchers from a variety of institutions, mainly from the US and Sweden, including the California Institute of Technology, Rush University Medical Center in Chicago and Chalmers University of Technology in Sweden.

It was funded by the Knut and Alice Wallenberg Foundation and the Swedish Research Council.

The study was published in the peer-reviewed scientific journal Cell. It’s available on an open-access basis and is free to read online.

Generally the UK media coverage on this topic was balanced, although the Mail Online did say this study “could overhaul medical research and treatment of Parkinson’s” which is possibly over optimistic. 

What kind of research was this?

This was an animal study which aimed to investigate a possible link between gut bacteria and brain diseases such as Parkinson’s disease.

Parkinson’s is a disease of unknown cause where there is a loss of dopamine-producing cells in the brain. This leads to  progressive decline in brain and motor function. Typical symptoms include slow movements, stiff muscles and involuntary shaking and there are  often mental health effects such as depression and dementia.

Past evidence has suggested that gut bacteria could influence the development of brain diseases such as Parkinson’s by causing build-up of the protein alpha-synuclein (α-synuclein).

However, there was a lack of studies investigating the link through cellular research, an issue the researchers wanted to address.

Animal studies are useful early stage research which can indicate how processes in the body may work. On the other hand, mice and humans are quite different in biology so what works in mice may not necessarily be the same in humans. And even if the findings do apply, they may not provide the whole answer to the causes of diseases such as Parkinson’s.

What did the research involve?

The research involved two groups of mice aged 12-13 weeks. One group of mice was genetically programmed to produce the protein alpha-synuclein (α-synuclein), which is thought to build up in people with degenerative brain conditions like Parkinson’s. Another group of “normal” mice acted as controls.

Within these two groups, the gut composition of the mice was changed. Some mice remained germ-free, some were given gut bacteria from “healthy” donors, and others were given gut bacteria from people with Parkinson’s.

The brain and motor function was tested over time in all groups of mice, along with gastrointestinal tests, up to the age of 24-25 weeks. Standardised testing, used for mice, was used to assess motor function. 

The test results were compared between the different groups of mice to see whether gut bacteria composition, in combination with the protein, had any effect on the onset of Parkinson-like symptoms.

What were the basic results?

Overall, they found that a decrease in motor function for mice with gut microbes compared with those who remained germ-free.

• The presence of gut bacteria promoted the decline in motor function caused by α-synuclein. Mice genetically modified to produce this protein and then given gut bacteria generally performed the worst in the motor function tests. Gut bacteria from people with Parkinson’s caused the greatest decline in motor dysfunction.
• Mice producing α-synuclein who remained germ-free still showed a decline in motor function by 24-25 weeks old, but the onset was significantly slower compared to the mice with gut bacteria. 
• The researchers found that gut microbes seemed to be affecting brain function via the action of short-chain fatty acids. The microbes produce short-chain fatty acids. The acids then causes an inflammatory response in the brain’s immune cells (microglia) which leads to the dysfunction. 
• In the germ-free mice there was no fatty acid signalling, limited inflammatory effect and limited motor dysfunction.

How did the researchers interpret the results?

The researchers concluded:“remarkably, colonization of aSyn-overexpressing mice with microbiota from [people with Parkinson’s] enhances physical impairments compared to microbiota transplants from healthy human donors.”

“These findings reveal that gut bacteria regulate movement disorders in mice and suggest that alterations in the human microbiome represent a risk factor for Parkinson’s disease.”

Conclusion

This study aimed to investigate a possible link between gut bacteria and degenerative brain diseases such as Parkinson’s.

In the animal model of Parkinson’s, researchers found that the presence of gut bacteria seems to enhance the brain’s inflammatory response and lead to greater decrease in motor function.

And gut bacteria from people with Parkinson’s seemed to have the greatest effect.

But does this mean that Parkinson’s is essentially a gut disorder and could potentially be treated or prevented with antibiotics? Unfortunately the answer isn’t so simple.

Although these are interesting findings, biological function in mice isn’t exactly the same as in humans, so you can’t necessarily apply these findings to the human population.

Even if they are applicable in part, this still may not provide the whole answer as to how the disease process of Parkinson’s starts. However, it does act as useful early stage research which could pave the way for further studies in humans.

Dr. Arthur Roach, Director of Research and Development at Parkinson’s UK commented on this study:

“This paper shows for the first time a way in which one of the key players in Parkinson’s, the protein alpha-synuclein, may have its actions in the brain modified by gut bacteria. It is important to note however that this study has been done in mice and we would need further studies in other model systems and in humans to confirm that this connection is real … There are still many questions to answer but we hope this will trigger more research that will ultimately revolutionise treatment options for Parkinson’s.”

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Links To The Headlines

Parkinson’s disease ‘may start in gut’. BBC News, December 2 2016

Parkinson’s could start in the GUT not the brain: Study finds first ever link between the disease and gut microbes. Mail Online, December 1 2016

Links To Science

Sampson TR, Debelius JW, Thorn T, et al. Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson’s Disease. Cell. Published online December 1 2016