Caltech study finds link between Parkinson's disease and gut bacteria

Artist’s concept depicting microbes in the gut instigating changes in the brain that can lead to Parkinson’s disease. People with Parkinson’s harbor distinct gut bacteria that influence the disease’s severity.
Artist’s concept depicting microbes in the gut instigating changes in the brain that can lead to Parkinson’s disease. People with Parkinson’s harbor distinct gut bacteria that influence the disease’s severity. Caltech

Parkinson's is often seen as a disorder of the brain, but a new study from Caltech highlights the key role gut bacteria may play in this debilitating disease.

The new findings suggest there may soon be new ways to treat the disorder that already affects one million Americans and is expected to be even more common as the U.S. population ages.

The study also backs up a growing body of research looking into the connection between the brain and the microbiome, a fancy term for the billions of tiny bacteria living inside our guts.

Here's how the study worked: the researchers took mice prone to Parkinson's like symptoms and raised some in a sterile, microbe-free environment and others in our naturally germ-covered world.

Both groups of mice had been bred to overproduce a protein called alpha-synuclein, a biomolecule associated with the progression of Parkinson's disease.

The researchers then tested both groups with a sort of mice gymnastics routine, which involved walking a long beam, crawling down a pole and removing a sticker placed on each animal's face. All of it was timed.

The mice with everyday bacteria living in their guts struggled with these tests, showing the same type of motor difficulties as Parkinson's patients. 

But the mice in the sterile environment climbed and moved without much problem, suggesting that gut bacteria were crucial in the development of these symptoms.

"I really wasn't expecting it at all," said Timothy Sampson, a Caltech biologist and co-author of the study, which appears in the December 1st issue of the prestigious journal Cell. "The idea that gut microbes could be influencing such a strong motor function was really surprising."

This cage is where the sterile mice performed their gymnastics tests. You can see the beam they walked across at the bottom, it narrows as it progresses to further test the motor control of the mice.
This cage is where the sterile mice performed their gymnastics tests. You can see the beam they walked across at the bottom, it narrows as it progresses to further test the motor control of the mice. Timothy Sampson

Sampson and his team later gave the sterile mice small fecal transplants from human patients with Parkinson's.

It's an unsavory idea to be sure, but it revealed something fascinating: once exposed to the bacteria of a Parkinson's patient, the formerly symptom-free mice developed motor-control problems.

Even more surprising, when the germ-laden mice were given powerful antibiotics that wiped out much of their microbiome, they gained back a lot of their motor control.

Despite this, Sampson and others don't think bacteria are causing Parkinson's to develop. Past research suggests a variety of factors are involved, including environment and genetics.

For instance, Sampson's team also experimented with mice that weren't prone to Parkinson's symptoms. When they gave these animals fecal samples from Parkinson's patients, they didn't develop motor control problems, suggesting there is more than bacteria involved.

"It certainly suggests there is active signaling that's occurring between microbes and the brain during adulthood that is influencing diseases," Sampson explained.

It's important to note, studies involving mice often don't apply to people, and diseases like Parkinson's are quite complex.

However, previous studies have shown a similar gut and brain connection in human Parkinson's patients, suggesting this research might offer valuable insights.

In fact, a number of other studies have shown a link between our gut bacteria and neurological disorders like autism and anxiety, said Sarkis Mazmanian, a Caltech microbiologist and an advisor on the study.

"It doesn't imply that all bacteria are bad," Mazmanian said.

We need our microbiomes for many important biological functions, he said, like breaking down food and staying healthy. So Parkinson's patients should not consider using antibiotics to clean out their guts, he warned.

"Ultimately, what this shows is there are potentially different classes of organisms," he said.

If we can identify which microbes are harmful and lead to Parkinson's and which are beneficial, we could develop probiotic treatments for this and other diseases, Mazmanian said.

That's an exciting idea for many in this field since current Parkinson's medications targeting the brain can have lots of negative side effects.

"This is a very intriguing finding," said Neal Hermanowicz, director of the Parkinson's Disease and Movement Disorders program at UC Irvine. He was not involved with this study.

Other research has shown the link between gut health and Parkinson's in humans, Hermanowicz said, and bowel disorders like constipation often precede the onset of the disease.

Evidence suggests the communication between the bowls and the brain might happen along the vagus nerve, a major nerve pathway in our bodies.

Hermanowicz said some patients who have had this nerve severed for other reasons, like treating severe ulcers, appeared to have a reduced risk of developing Parkinson's later in life.

So how long until all this research is translated into new treatments?

"I'm an optimistic guy," said Hermanowicz. "I'm hoping that within the next five years [this field of research] will be the springboard for therapeutic interventions."

Next, Caltech's Sampson hopes to investigate other aspects of the gut's role in Parkinson's disease.

"I think for me, the most exciting question is understanding if there's particular species of bacteria that are more abundant in Parkinson's disease patients," he said.

That means he'll need to head back to the lab to look for more clues in the emerging field of gut and brain research.

Caltech researchers explain the link between gut bacteria and Parkinson's disease

This story has been updated.

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