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New Evidence Suggests Parkinson's Might Start in The Gut, Not The Brain

We might have been wrong about Parkinson's this whole time.

FIONA MACDONALD
5 DEC 2016
 

A new study adds to a growing body of research that suggests we might have been thinking about Parkinson's disease wrong this whole time.

Instead of being isolated to the brain, new evidence in mice suggests that the condition might actually start in the gut. And it could explain some of the strange coincidences seen in the disease, such as why most Parkinson's patients complain of constipation up to a decade before other symptoms arise.

 

Parkinson's disease is most commonly associated with tremors, stiffness, and difficulty moving, caused by neurons deep in the brain being killed off.

Although there are treatments to slow the progress of the condition, there's no way to prevent or cure it, and researchers still don't really understand what causes it and how it progresses.

For years, scientists have limited the search for the cause of Parkinson's to the brain, but a growing body of evidence suggests that might be the wrong approach.

Parkinson's might actually originate in the gut before spreading to the brain, it could explain some of the strange links researchers have seen with Parkinson's patients.

Researchers have noticed that people with Parkinson's often report constipation, as well as other digestive problems, up to 10 years before they notice tremors. There's also evidence that people with Parkinson's disease have different gut bacteria to other healthy adults.

Now a new study in mice has shown that the toxic fibres that build up around the nerve cells of Parkinson's patients can influence the nerves in the brain in a matter of weeks.

 

"We have discovered for the first time a biological link between the gut microbiome and Parkinson's disease," said lead researcher Sarkis Mazmanian from the Californian Institute of Technology (Caltech).

"More generally, this research reveals that a neurodegenerative disease may have its origins in the gut, and not only in the brain as had been previously thought."

The team found this out by looking at the spread of toxic fibres made of a substance known as alpha-synuclein.

Alpha-synuclein is small and soluble in healthy nerve cells, but for some reason, in Parkinson's patients, these alpha-synuclein molecules clump together and form fibres that damage the nerves in the brain.

Around a decade ago, researchers began to report that patients who had these fibres in their brains also had them in their gut.

In the latest study, the Caltech team looked at mice that had been genetically modified to be susceptible to Parkinson's disease, by over-producing alpha-synuclein fibres.

These mice were either raised in normal, non-sterile cages, or in a sterile, germ-free environment.

Mice raised in the germ-free cages showed fewer motor deficits, and less toxic fibres in their brains. But mice raised in the non-sterile environment developed Parkinson's symptoms as expected, given their genetic predisposition.

Antibiotic treatment was able to reduce these symptoms in the non-sterile mice, suggesting there was something in their microbiome that was enhancing the symptoms.

Finally, the team injected gut bacteria from human Parkinson's patients into the germ-free mice. They quickly went from showing hardly any symptoms to deteriorating rapidly.

Gut bacteria taken from healthy people didn't have the same effect.

"This was the 'eureka' moment, the mice were genetically identical, the only difference was the presence or absence of gut microbiota," said one of the team, Timothy Sampson.

"Now we were quite confident that gut bacteria regulate, and are even required for, the symptoms of Parkinson's disease."

The scientists think that the gut bacteria might be releasing chemicals that over-activate parts of the brain, leading to damage. 

There's a lot more research to be done before we can say for sure what's going on, but if this research can be verified and replicated, it could change the way we treat the condition forever.

"That would be game-changing," David Burn, from Newcastle University in the UK, who wasn't involved in the study, told Clare Wilson for New Scientist. "There are lots of different mechanisms that could potentially stop the spread."

The team presented their work at the Society for Neuroscience meeting in San Diego last month, and have now published the results in Cell.

It's important to note that mouse studies often don't translate to human health, and we still don't have the full picture of what's going on here - there might be other important factors involved.

Other studies have shown that people exposed to certain pesticides are more likely to get Parkinson's, so the team thinks that maybe these chemicals could be affecting gut bacteria.

The team now want to analyse the gut microbiomes of people with Parkinson's to try to narrow down which microbes seem to be predisposing people to the disease.

If they could identify certain strains, it means scientists could find a way to screen for Parkinson's before symptoms appear and the damage to the brain occurs. It could also help them come up with new treatment options.

"Much like any other drug discovery process, translating this innovative work from mice to humans will take many years," said Mazmanian. "But this is an important first step." 

The research has been published in Cell.

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