Gut microbes may spark Parkinson's: bacterial imbalance could be culprit, mouse study suggests.
Intestinal microbes send signals that set off the disease's characteristic brain inflammation and movement problems in mice, researchers report in the Dec. 1 Cell. Doctors might someday be able to treat Parkinson's by fixing this bacterial imbalance.
"It's quite an exciting piece of work," says John Cryan, a neuroscientist at University College Cork in Ireland who wasn't involved in the study. "The relationship between the brain and gut for Parkinson's has been bubbling up for many years." The new research, he says, "brings the microbiome really into the forefront for the first time."
Parkinson's affects more than 10 million people worldwide, and roughly 70 percent of those patients also have gastrointestinal issues like constipation. Sometimes the GI symptoms show up years before the muscle weakness and other neurological problems. Several recent studies in humans have suggested a link between gut microbes and Parkinson's. But it hasn't been clear whether intestinal microbes actually cause the disease, says study coauthor Sarkis Mazmanian, a microbiologist at Caltech. "What our study adds is a functional, mechanistic role for the microbiome."
Mazmanian's team studied mice bred to produce too much alpha-synuclein, the protein that's believed to cause Parkinson's when it clumps in the brain. Mice with extra alpha-synuclein acted like they had Parkinson's: They traversed a narrow beam more slowly, they couldn't grip a pole as well and they struggled to pull stickers off their noses. Their brains showed signs of inflammation, too. But when the researchers raised the same type of mice to be germfree --that is, with no gut microbes--the animals acted less sick.
Those mice were still producing boatloads of alpha-synuclein, but the protein wasn't clumping as much in their brains. Without the clumps, the mice didn't have as much of the unsteady gait and muscle weakness typical of Parkinson's--and in fact, some of the mice acted completely healthy.
In another experiment, the researchers transferred gut microbes from Parkinson's patients into germ-free mice making too much alpha-synuclein. Those mice developed motor problems when tested six or seven weeks after the transfer, but mice who got microbes from healthy humans were fine.
"Even though the mice that received the healthy microbiota received hundreds of bacteria, they didn't get the disease," Mazmanian says. That suggests it's not the presence or absence of bacteria that triggers Parkinson's but the specific composition of the microbial cocktail.
Alpha-synuclein clumps can move from the gut to the brain (SN: 12/10/16, p. 12), a recent study showed. It seems that gut bacteria themselves are also sending important signals.
Researchers are now trying to figure out which signals--and which microbes--throw off the balance.
Fecal samples from the mice implanted with bacteria from Parkinson's patients had higher than normal levels of certain gut bacteria. That imbalance could be sparking symptoms, says study coauthor Tim Sampson, a Caltech microbiologist. "I'm interested in trying to understand if there are potential pathogenic microbes that might be individually driving the disease," he says. "Once we've figured that out, we'll be able to understand whether we can remove that group of organisms or block them."
Abnormally low levels of helpful bacteria could also factor in. The new analyses aren't large enough to firmly conclude which microbes are particularly important players. But if scientists can figure out what those missing beneficial bacteria are, Mazmanian says, targeted probiotic therapy might be a treatment option in the future.
Aging-associated diseases such as Parkinson's are tricky to study in a mouse model, cautions Stanford University microbiologist Justin Sonnenburg. "They're typically the result of decades of accumulations of problems," whereas the mice in the current study were just a couple months old. So the findings will need to be validated in human studies before influencing treatments. Still, he says, "it's a really important contribution to the growing list of ways that gut microbes can alter our health."
Caption: Signals from gut microbes can activate immune cells called microglia (shown here in green) in the mouse brain, causing inflammation that's characteristic of Parkinson's disease.
Please note: Illustration(s) are not available due to copyright restrictions.
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|Title Annotation:||BODY & BRAIN|
|Date:||Dec 24, 2016|
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