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Study: Gut Bacteria May Lead to Parkinson’s Disease

Artist’s concept depicting microbes in the gut instigating changes in the brain that can lead to Parkinson’s disease. People with Parkinson’s harbor distinct gut bacteria that influence the disease’s severity. (CalTech)
Artist’s concept depicting microbes in the gut instigating changes in the brain that can lead to Parkinson’s disease. People with Parkinson’s harbor distinct gut bacteria that influence the disease’s severity. (CalTech)

Parkinson’s disease may be linked to certain gut bacteria, according to a new study.

Writing in the journal Cell, researchers at the California Institute of Technology say: “Changes in the composition of gut bacterial populations—or possibly gut bacteria themselves—are actively contributing to and may even cause the deterioration of motor skills that is the hallmark of this disease.”

Parkinson’s is a neurodegenerative disease that affects some 10 million people around the world and one million Americans. Symptoms include tremors and difficulty walking. It has no known cure.

Researchers say 75 percent of Parkinson’s sufferers have gastrointestinal (GI) “abnormalities,” usually constipation.

The new findings about the connection of gut bacteria to the disease could lead to new treatments that could, for example, help good bacteria develop or kill unwanted microbes.

"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," said researcher Sarkis Mazmanian. "Remarkably, 70 percent of all neurons in the peripheral nervous system—that is, not the brain or spinal cord—are in the intestines, and the gut's nervous system is directly connected to the central nervous system through the vagus nerve. Because GI problems often precede the motor symptoms by many years, and because most [Parkinson’s] cases are caused by environmental factors, we hypothesized that bacteria in the gut may contribute to [Parkinson’s]."

Researchers reached their conclusion after testing mice that were programmed to produce high levels of a protein called alpha-synuclein (αSyn), which is associated with damage in the brain in Parkinson’s patients.

The mice were divided into two groups. One group had a consortium of gut bacteria in their systems, while the other were “germ-free” and had no gut bacteria.

Researchers then compared the motor skills of each group and found that the germ-free mice performed better.

"This was the 'eureka' moment," says Timothy Sampson, a postdoctoral scholar in biology and biological engineering. "The mice were genetically identical; both groups were making too much αSyn. The only difference was the presence or absence of gut microbiota. Once you remove the microbiome, the mice have normal motor skills even with the overproduction of αSyn.

"All three of the hallmark traits of Parkinson's were gone in the germ-free models," Sampson added. "Now we were quite confident that gut bacteria regulate, and are even required for, the symptoms of Parkinson's disease. So, we wanted to know how this happens."

Researchers think when gut bacteria break down dietary fiber, they produce molecules called short-chain fatty acids (SCFA), which prior research has shown can “activate immune responses in the brain,” potentially causing damage to neurons.

"This really closed the loop for us," Mazmanian said. "The data suggest that changes to the gut microbiome are likely more than just a consequence of Parkinson’s. It's a provocative finding that needs to be further studied, but the fact that you can transplant the microbiome from humans to mice and transfer symptoms suggests that bacteria are a major contributor to disease."

The findings need to be confirmed on humans, but since we require trillions of gut bacteria to live, making someone germ-free would not be feasible.

"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," Mazmanian says. "Such drugs could be designed to modulate SCFA levels, deliver beneficial probiotics, or remove harmful organisms. This new concept may lead to safer therapies with fewer side effects compared to current treatments."

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