The germs living inside a person’s digestive system may affect symptoms of Parkinson’s disease, researchers reported Thursday.
Tests done on mice showed their symptoms worsened when they were dosed with microbes taken from human Parkinson’s patients but not when they got samples from healthy patients. And other tests on mice that develop Parkinson’s-like symptoms showed they only developed symptoms if they had gut germs to begin with.
The study doesn’t show that gut microbes cause Parkinson’s, but they may suggest a way to treat the incurable condition, which affects up to a million Americans and 10 million people worldwide.
“I think it is going to be one of these groundbreaking pieces of research,” said James Beck, vice president for scientific affairs at the Parkinson’s Disease Foundation, which was not involved in the research.
“It might lead to new therapies.”
Parkinson’s is marked by tremor, rigid muscles and problems with movement. While early treatment can delay the worst symptoms, people almost always get worse. About 60,000 Americans are diagnosed with Parkinson's disease each year.
It’s a brain disease, characterized by the buildup of a protein called alpha-synuclein.
So how could intestinal microbes affect it?
Many studies have shown the bacteria, viruses, yeast and fungi living in and on the body, collectively called the microbiome, directly affect health. Not only do they help digest food, but different balances of the microorganisms may influence diseases all over the body, from cancer to autism.
Sarkis Mazmanian and colleagues at the California Institute of Technology had seen previous studies that showed people with Parkinson’s had gut microbiomes that looked different from those of people without Parkinson’s.
“There are particular classes of bacteria that are selectively missing or depleted in the Parkinson’s population and found in the healthy population,” Mazmanian told NBC News.
"All three of the hallmark traits of Parkinson's were gone in the germ-free models."
There are hundreds and even thousands of different species of bacteria in the intestines, and different people have different balances and, sometimes, completely different populations. It will be years before anyone nails down the precise bacteria that might help or worsen Parkinson’s.
And first, the link must be proven. Mazmanian’s team took a big step by using mice bred to develop Parkinson’s symptoms because they overproduce alpha-synuclein in their brains.
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In one experiment, they showed that mice born in a completely sterile environment and which have limited microbiomes do not develop Parkinson’s symptoms, even as their brains are clogged with alpha-synuclein. Mice raised in normal, germy environments did develop symptoms.
"All three of the hallmark traits of Parkinson's were gone in the germ-free models," said Timothy Sampson, a Caltech researcher who worked on the study.
"Now we were quite confident that gut bacteria regulate, and are even required for, the symptoms of Parkinson’s disease.”
Giving germs to the mice changed things.
“When we transferred microbiota from Parkinson’s disease patients, the mice developed more severe symptoms than when they got microbiota from healthy controls,” Mazmanian said.
“It’s mouse research and doesn’t mean we’ve done anything yet to help people."
How might it happen? It could be that breakdown products of the bacteria are toxic and circulate to the brain, Mazmanian said. There are also many nerve connections between the intestines and the brain and it could be that influencing the nerves in the gut affects nerves in the brain.
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“Coupled with emerging research that has linked gut bacteria to disorders such as anxiety, depression, and autism, we propose the provocative hypothesis that certain neurologic conditions that have classically been studied as disorders of the brain may also have etiologies in the gut,” the researchers wrote in their report, published in the journal Cell.
That could be good news for treating the disease.
"For many neurological conditions, the conventional treatment approach is to get a drug into the brain. However, if Parkinson’s disease is indeed not solely caused by changes in the brain but instead by changes in the microbiome, then you may just have to get drugs into the gut to help patients, which is much easier to do," said Mazmanian, who has founded a company called Axial Biotherapeutics to explore possible treatments.
He is cautious.
“It’s mouse research and doesn’t mean we’ve done anything yet to help people,” Mazmanian sad.
He is also aware that companies are already selling probiotics with the promise they can treat a range of diseases. There is no proof behind any of them. Researchers don’t even know all of the species of organisms living inside the human gut, let alone which ones may influence which diseases.
“I am sure sensational claims will be made,” Mazmanian said. “I have seen people misrepresent our research. This research opens doors but it doesn’t mean that we have solved the problem of Parkinson’s disease.”
Beck notes that there has been mixed evidence on the use of antibiotics to treat Parkinson’s. Sometimes they seem to help. But it would be dangerous to try before researchers can decide if Parkinson’s patients are lacking the “right” microbes, have too many of the “wrong” ones, or if something else altogether is going on.
"It is important to note that there are currently no antibiotic or microbial treatments available for human use that can replicate the effect we observed in mice,” Mazmanian’s team pointed out.