Scientists from the California Institute of Technology (Caltech) have discovered a link between gut bacteria and Parkinson’s disease that could bring them one step closer to finding the cause of the nervous system disorder and potentially opening a new avenue for treatment.
The study, published Thursday in the journal Cell, found that intestinal microbes, or changes within those bacteria, contribute to and could potentially even be the cause of motor dysfunctions associated with Parkinson’s, Healthline and the Pasadena Star-News reported this week.
Patients suffering from Parkinson’s experience an accumulation of alpha-synuclein protein or αSyn within cells in the brain, as well as cytokines (inflammatory molecules) in the brain itself. In addition, approximately three-fourths of them experience gastrointestinal (GI) abnormalities, primarily constipation, prior to the appearance of other symptoms, the study authors said.
Because of this, researchers have long theorized that GI tract or gut bacteria were related to the decline in motor skills in Parkinson’s patients. The new study provides evidence to support that notion by proving that such symptoms appeared in mice after they received a transplant of fecal bacteria from humans suffering from the degenerative neurological condition.
Microbe-less mice performed better on motor function tests
As lead author Dr. Sarkis Mazmanian, a microbiologist at Caltech as well as an investigator at the Heritage Medical Research Institute, explained in a statement, “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.”
“Remarkably, 70% 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,” he added. “Because GI problems often precede the motor symptoms by many years, and because most PD cases are caused by environmental factors, we hypothesized that bacteria in the gut may contribute to PD.”
To put their hypothesis to the test, Dr. Mazmanian and his colleagues used mice subjects which tended to overproduce αSyn and display symptoms of Parkinson’s disease. They divided the mice into two groups: one with a complex array of gut bacteria, and another that were bred in a sterile environment and which lacked GI microbes. Both groups underwent several tests to demonstrate their motor skills. The bacteria-less group performed significantly better.
“This was the ‘eureka’ moment,” said Timothy Sampson, a postdoctoral scholar in biology and biological engineering and first author of the new paper. “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.”
Discovery could lead to new, microbiome-based treatments
Now confident that GI tract bacteria “regulate, and are even required for, the symptoms of PD,” Sampson said that the researchers set out to determine exactly why this was the case. Since gut bacteria produce molecules known as short-chain fatty acids (SCFAs) that can activate immune responses in the brain when they break down dietary fiber, they started looking there.
Feeding SCFAs to the bacteria-free mice resulted the activation of immune cells in the brain, as well as motor disabilities and αSyn aggregation in regions of the brain linked to Parkinson’s, the researchers explained. In another set of experiments, they obtained fecal samples from patients with the disease and transplanted them into the microbe-free group of mice. Those mice began to show symptoms of Parkinson’s and had elevated levels of SCFAs in their feces.
“This really closed the loop for us,” said Mazmanian. “The data suggest that changes to the gut microbiome are likely more than just a consequence of PD. 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.”
“For many neurological conditions, the conventional treatment approach is to get a drug into the brain. However, if PD 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,” he concluded. “This new concept may lead to safer therapies with fewer side effects compared to current treatments.”
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