A new study adds further evidence to a growing number of research breakthroughs which suggests that Parkinson's (PD) originates in the gut and not the brain. New research outcomes in mice suggest PD might actually start in the gut and this might explain why most Parkinson's patients complain of constipation and gut-related symptoms before other symptoms arise.

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

Now a new study in mice has shown that the toxic alpha-synuclein fibres that build up in the nerve (neuron) endings of PD patients can influence brain neurons in a matter of weeks.

We have discovered for the first time a biological link between the gut microbiome (microorganisms found in association with both healthy and diseased humans) and Parkinson's disease. 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.

- Sarkis Mazmanian, lead researcher the Californian Institute of Technology (Caltech).

The team discovered this by looking at the spread of the alpha-synuclein fibres. Alpha-synuclein is small and soluble in healthy neurons, but for some reason, in PD patients, these alpha-synuclein molecules clump together and damage the neurons in the brain.

Approximately ten years ago, researchers began to report that patients who had alpha-synuclein in their brains also had it in their gut.

In the latest study, the Caltech team looked at genetically modified mice (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 alpha-synuclein in their brains. But mice raised in the non-sterile environment developed Parkinson's symptoms as expected, given their genetic predisposition. Antibiotics given to these mice reduced 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 PD 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 responsible for chemicals which are over-activating parts of the brain, leading to alpha-synuclein damage. 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 involved in the research breakthrough now want to analyse the gut microbiomes of people with PD 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.

The Cure Parkinson's Trust has long been interested in the link between alpha-synuclein and PD and our ongoing research in this area bears testament to this:

- Professor Maria Spillantini - a-synuclein aggregation
- Professor Roger Barker - RVG9R-p137
- Dr Javier Alegre Abarrátegui – LRKK2
- Flint Beal- DPufas

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Excerpts for this article were taken from the online magazine: Thelightmedia.com

This research has been published in Cell.