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Could Parkinson's Disease Start in the Gut Rather Than in the Brain?

by Kristina C. - December 19, 2016


Photo Credit: by Kristina Campbell
Photo Credit: by Kristina Campbell

When Parkinson's disease happens to someone you love, the slowing down can seem to happen... well, slowly. Nothing seems to be wrong until you start to notice their movements aren't as quick and precise as they once were. You see them struggling to open a doorknob. You notice a tiny tremor in one hand when they're sitting, and they complain about ongoing sleep problems. You tell yourself it’s just because they’re getting older.

And then the diagnosis makes it clearer. It's Parkinson's disease (PD) — a nervous system disorder involving movement symptoms like tremors, slowness, and stiffness, as well as non-motor symptoms like digestive and sleep problems. What's clear is that your loved one will never move quickly again, that their muscles will be constantly seeking to betray them. You’ll learn that medications can ease the symptoms for a period of time, but the disease will keep on progressing.

A new line of research, however, is bringing hope for better ways to treat PD—or even prevent it in the first place. Scientists are looking for its origin in an unexpected place: the digestive tract and the trillions of live microbes (like bacteria, fungi, and viruses) living there.

It started with research showing that a substance called synuclein, which exists normally in the body, abnormally clumps together into fibers in individuals with Parkinson’s disease. These fibers were observed both in the gut and in the brain, but no one knew what caused them.

Meanwhile, scientists at several different centers around the world noticed that individuals with PD tended to have different microbes making up their feces than healthy individuals. The studies didn’t agree on exactly which bacterial makeup was unique to people with PD, although there was a curious trend of increased Akkermansia muciniphila (bacteria usually associated with good metabolic health) and decreased Faecalibacterium prausnitzii (anti-inflammatory bacteria). Nevertheless, something about the gut microbial community was different in the disease.

According to breaking research from the California Institute of Technology, a connection between synuclein fibers and different microbial communities could exist. Researchers just released a study using mice with too much of the potentially-clumping protein alpha-synuclein (αSyn); over their lifespans, these mice show a gradual decline in motor function as well as problems with how food moves through their digestive tracts (similar to people with PD). The researchers colonized these mice with different communities of bacteria, or none at all, and watched what happened to their symptoms.

They found that if the mice had no microbiota (i.e. they were germ-free), the motor deficits that showed up were significantly delayed and the mice had fewer clumps of αSyn in their brains. Not only that, but these germ-free mice avoided the constipation that was present in the mice with normal microbial communities. More interestingly, when the researchers took gut microbes from humans with PD and transplanted them into the mice, the transplants seemed to make the mice’s motor problems worse. This was the first study to show a possible cause-and-effect relationship between gut microbes and the symptoms (in mice) that characterize human Parkinson’s disease.

At first glance it might seem strange to look to the gut for the cause of PD—a brain disorder—but doctors have in fact known about the gut-brain connection in this disease for some time. For example, constipation is the greatest risk factor for the later development of PD, and it often precedes the motor symptoms by many years. Other studies have shown that individuals with PD have increased intestinal inflammation. Doctors already know just how much these digestive problems bother their patients: in the early stages after PD diagnosis, patients tend to say the gut symptoms have a much bigger impact on their quality of life than the motor symptoms.

If this connection between gut microorganisms and PD bears out in future experiments, it would mean that the process leading to PD starts a lot earlier than we ever knew—and it would also mean we might be able to develop a biomarker to detect PD early. The possibility also exist for developing ways to steer the gut microbial community in the right direction before any motor symptoms show up. At the very least, if we could harness gut microbes to slow down the slowing down, it could be a game changer for millions of families.

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Kristina Campbell is a freelance science writer specializing in the gut microbiota and digestive health.


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