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New evidence from a mouse study supports the notion that Parkinson’s disease could start in the gut. Image credit: Westend61/Getty Images.
  • Researchers from Columbia University Irving Medical Center in New York City recently conducted a study in mice to see if they could find out more about how Parkinson’s disease and changes in the gut are connected.
  • Parkinson’s disease causes neurological changes that affect motor skills and may eventually lead to losing the ability to walk.
  • The researchers suspected that a protein connected with Parkinson’s impacts people via the gut, years before they show hallmark symptoms of the disease.
  • The scientists created an injection to administer to two groups of mice — one group was regular and the other was engineered to have similar genetic factors as humans in terms of developing Parkinson’s disorder.
  • They suspected that the engineered mice would respond to the injection by exhibiting gastrointestinal symptoms, as people with Parkinson’s disease may experience.

While researchers know Parkinson’s disease affects the brain, they wonder whether it is possible that instead of the disease originating in the brain, it starts in the gut by way of an immune system response.

Some studies show a link between the gut microbiome and Parkinson’s. Researchers from Columbia University have now expanded on this line of research in a new study, which appears in the journal Neuron.

After giving both groups of mice the injection they believed would trigger an immune system response — and thus gastrointestinal symptoms — the group of mice with human traits not only experienced constipation but also had nerve cell damage in their guts.

The researchers want to continue this line of research and see if they can eventually detect damage in the brain as well.

Parkinson’s disease, a type of movement disorder, can cause nerve cells to degenerate. When this happens, people with the disease may experience stiffness, tremors, shaking, and other uncontrollable movements.

Doctors diagnose the disease after ruling out other physiological causes for symptoms.

Before experiencing movement difficulties, there are other symptoms that people would not necessarily connect with Parkinson’s disease.

According to the existing research, in this phase of the disease, people may experience some of the following issues:

According to the study authors, many people who develop Parkinson’s report experiencing constipation and other gastrointestinal symptoms up to 20 years prior to developing motor symptoms.

“Constipation presents in approximately 70% of Parkinson’s disease patients,” report the authors.

Alpha-synuclein, a protein found in the body, becomes misfolded in people with Parkinson’s disease, and this misfolding contributes to the progression of the disease.

The misfolded protein that appears on neurons in the brain can also be found in the gut, which led the researchers to wonder whether the immune system is involved in the disease development.

“The blood of Parkinson’s patients often contains immune cells that are primed to attack the neurons,” said study author and neurobiologist Prof. David Sulzer in a press release. “But it’s not clear where or when they are primed.”

This contributed to the researchers deciding to focus on seeing if they could cause gastrointestinal symptoms in mice that they engineered to have misfolded alpha-synuclein.

The scientists created an alpha-synuclein injection, which they administered to two groups of mice: regular mice and engineered mice.

They next monitored the mice for 6 weeks. In addition to checking for symptoms of gastric distress, they also kept track of how much the mice weighed.

At the end of the 6-week period of monitoring the mice, the researchers checked the nerve cells in the guts of the mice to assess for damage.

As the scientists monitored the mice following their injections, they noticed that both the regular mice and engineered mice became sick. This lasted for a short period of time, however, and then the regular mice were back to normal.

Yet 25% of the mice with the human gene remained sick after their alpha-synuclein injections. According to the researchers, these mice began losing weight, which occurred between 22 and 24 days post-injection.

The mice with the weight loss regained the weight by day 29. However, the researchers said these mice experienced a severely affected “gastrointestinal transit time.”

In other words, the mice experienced constipation. The scientists noticed this side effect only in the mice with the human gene that also experienced weight loss — the regular mice and the engineered mice with no weight loss did not experience this level of constipation.

This led the researchers to conclude that the alpha-synuclein injections combined with the human gene in the mice have the potential to cause gut problems.

While these findings add another reason to believe that Parkinson’s may start in the gut, the scientists did not see any changes in the brains of the mice. They hope to expand on this research one day.

“Our ultimate goal is to develop a model of Parkinson’s disease in mice that recreates the human disease process, which doesn’t exist right now,” said Prof. Sulzer in the press release.

Dr. Sameea Husain, director of movement disorder neurology with Marcus Neuroscience Institute, part of Baptist Health, at Bethesda Hospital East in Boynton Beach, Florida, spoke with Medical News Today about the study.

Dr. Wilson emphasized the importance of learning more about how the gut is connected to Parkinson’s.

“As scientists and researchers of the disease, we can more closely focus our efforts on studying the gut of these patients at a cellular level,” she said.

“We can study the bacteria that are found in the gut of [Parkinson’s disease] patients and see what different types exist,” Dr. Wilson continued. “We can juxtapose those bacteria with the bacteria found in people that do not have Parkinson’s and try to isolate them.”

She explained that they can look for genetic diseases and mutations and “may be able to someday identify which gut bacteria are solely responsible for the inflammation or genetic mutations that result in Parkinson’s disease.”

“This could result in the development of immunosuppressant medications that might lower the risk of developing Parkinson’s disease. We could also develop dietary recommendations or nutritional supplements that might improve the health of the gut and thereby lessen the presence of the bacteria that are responsible for causing Parkinson’s or even other diseases.”
— Dr. Sameea Husain Wilson