Los Angeles, December 3, 2016: For the first time, scientists have showed that Parkinson’s disease may be linked to changes in the gut bacteria and it can even cause the deterioration of motor skills that is the hallmark of the disorder.
Up to 10 million people worldwide is affected by Parkinson’s disease (PD), making it the second most common neurodegenerative disease.
According to PTI, Sarkis Mazmanian, California Institute of Technology in the US said, “The gut is a permanent home to a diverse community of beneficial and sometimes harmful bacteria, known as the microbiome, that is important for the development and function of the immune and nervous systems.”
“Because GI problems often precede the motor symptoms by many years, and because most PD cases are caused by environmental factors, we hypothesised that bacteria in the gut may contribute to PD,” he said.
Parkinson’s disease have symptoms like tremors, difficulty walking, aggregation of a protein called alpha-synuclein (aSyn) within cells in the gut and brain, and the presence of inflammatory molecules called cytokines within the brain. 75 per cent of people with PD have gastrointestinal (GI) abnormalities, primarily constipation
Researchers utilised mice to display symptoms of Parkinson’s.
According to PTI, “One group of mice had a complex consortium of gut bacteria; the others, called germ-free mice, were bred in a completely sterile environment and thus lacked gut bacteria.”
The researchers used both the groups of mice perform several tasks in order to measure their motor skills, such as running on treadmills, descending from a pole and crossing a beam.
The germ-free mice performed significantly better than that of the mice with a complete microbiome.
“Once you remove the microbiome, the mice have normal motor skills even with the overproduction of aSyn,” Sampson said.
“All three of the hallmark traits of Parkinson’s were gone in the germ-free models,” Sampson said.
When the gut bacteria break down dietary fibre, they produce molecules called short-chain fatty acids or SCFAs, such as acetate and butyrate.
Earlier research has shown that these molecules can activate immune responses in the brain. Therefore, Mazmanian’s group hypothesised that an imbalance in the levels of SCFAs regulates the brain inflammation and other symptoms of PD.
So, when germ-free mice were fed SCFAs, cells called microglia – which are immune cells residing in the brain-became activated.
In fact, such inflammatory processes can cause neurons to malfunction or even die.
When the germ-free mice fed SCFAs they showed motor disabilities and aSyn aggregation in the regions of the brain linked to the PD.
Scientists have found a new clue that Parkinson’s disease may get its start not in the brain but in the gut – maybe in the appendix.
People who had their appendix removed early in life had a lower risk of getting the tremor-inducing brain disease decades later, researchers reported Wednesday.
Why? A peek at surgically removed appendix tissue shows this tiny organ, often considered useless, seems to be a storage depot for an abnormal protein – one that, if it somehow makes its way into the brain, becomes a hallmark of Parkinson’s.
The big surprise, according to studies published in the journal Science Translational Medicine: Lots of people may harbor clumps of that worrisome protein in their appendix – young and old, people with healthy brains and those with Parkinson’s.
But don’t look for a surgeon just yet.
“We’re not saying to go out and get an appendectomy,” stressed Viviane Labrie of Michigan’s Van Andel Research Institute, a neuroscientist and geneticist who led the research team.
After all, there are plenty of people who have no appendix yet still develop Parkinson’s. And plenty of others harbor the culprit protein but never get sick, according to her research.
The gut connection
Doctors and patients have long known there’s some connection between the gastrointestinal tract and Parkinson’s. Constipation and other GI troubles are very common years before patients experience tremors and movement difficulty that lead to a Parkinson’s diagnosis.
Wednesday’s research promises to re-energize work to find out why, and learn who’s really at risk.
“This is a great piece of the puzzle. It’s a fundamental clue,” said Dr. Allison Willis, a Parkinson’s specialist at the University of Pennsylvania who wasn’t involved in the new studies but says her patients regularly ask about the gut link.
Parkinson’s Foundation chief scientific officer James Beck, who also wasn’t involved, agreed that “there’s a lot of tantalizing potential connections.”
He noted that despite its reputation, the appendix appears to play a role in immunity that may influence gut inflammation. The type of bacteria that live in the gut also may affect Parkinson’s.
But if it really is common to harbor that Parkinson’s-linked protein, “what we don’t know is what starts it, what gets this whole ball rolling,” Beck said.
For years, scientists have hypothesized about what might cause the gut-Parkinson’s connection. One main theory: Maybe bad “alpha-synuclein” protein can travel from nerve fibers in the GI tract up the vagus nerve, which connects the body’s major organs to the brain. Abnormal alpha-synuclein is toxic to brain cells involved with movement.
There have been prior clues. People who decades ago had the vagus nerve cut as part of a now-abandoned therapy had a reduced risk of Parkinson’s. Some smaller studies have suggested appendectomies, too, might be protective – but the results were conflicting.
Labrie’s team set out to find stronger evidence.
First, the researchers analyzed Sweden’s huge national health database, examining medical records of nearly 1.7 million people tracked since 1964. The risk of developing Parkinson’s was 19 percent lower among those who had their appendix surgically removed decades earlier.
One puzzling caveat: People living in rural areas appeared to get the benefit. Labrie said it’s possible that the appendix plays a role in environmental risk factors for Parkinson’s, such as pesticide exposure.
Further analysis suggested people who developed Parkinson’s despite an early-in-life appendectomy tended to have symptoms appear a few years later than similarly aged patients.
A common protein
That kind of study doesn’t prove that removing the appendix is what reduces the risk, cautioned Dr. Andrew Feigin, executive director of the Parkinson’s institute at NYU Langone Health, who wasn’t involved in Wednesday’s research.
So next, Labrie’s team examined appendix tissue from 48 Parkinson’s-free people. In 46 of them, the appendix harbored the abnormal Parkinson’s-linked protein. So did some Parkinson’s patients. Whether the appendix was inflamed or not also didn’t matter.
That’s a crucial finding because it means merely harboring the protein in the gut isn’t enough to trigger Parkinson’s, Labrie said. There has to be another step that makes it dangerous only for certain people.
“The difference we think is how you manage this pathology,” she said – how the body handles the buildup.
Her team plans additional studies to try to tell.
The reservoir finding is compelling, Feigin said, but another key question is if the abnormal protein also collects in healthy people’s intestines.