Research carried out by a team of American researchers has suggested that gut microbes may play a critical role in the development of Parkinson’s Disease (PD).
The findings could lead to new treatments that can slow, stop or even prevent the development of the condition.
Researchers based at the California Institute of Technology studied mice with a small genetic change that causes them to produce too much of the protein alpha-synuclein.
As the mice aged, they naturally developed clumps of alpha-synuclein inside brain areas involved in controlling movement similar to those experienced by people with Parkinson’s.
Mice raised in germ-free cages had almost normal mobility and much reduced build-up of protein clumps in their brains.
Parkinson’s affects ten million people worldwide, making it the second most common neurodegenerative disease, and 75% of sufferers have gastrointestinal (GI) abnormalities, primarily constipation.
The research was carried out in the laboratory of Sarkis Mazmanian, the Luis B. and Nelly Soux Professor of Microbiology and Heritage Medical Research Institute Investigator.
Sarkis said: “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. B
“Because GI problems often precede the motor symptoms by many years, and because most PD cases are caused by environmental factors, we hypothesised that bacteria in the gut may contribute to PD.”
The researchers used mice that over-produce αSyn and display symptoms of Parkinson’s. One group of mice had a complex consortium of gut bacteria and the others, called germ-free mice, were bred in a completely sterile environment at Caltech and thus lacked gut bacteria.
The researchers had both groups of mice perform several tasks to measure their motor skills, such as running on treadmills, crossing a beam, and descending from a pole. The germ-free mice performed significantly better than the mice with a complete microbiome.
Timothy Sampson, a postdoctoral scholar in biology and biological engineering and first author on the paper, said: “This was the ‘eureka’ moment. 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. Now we were quite confident that gut bacteria regulate, and are even required for, the symptoms of PD.”
In a final set of experiments, Sarkis Mazmanian and his group collaborated with Ali Keshavarzian, a gastroenterologist at Rush University in Chicago, to obtain fecal samples from patients with PD and from healthy controls. The human microbiome samples were transplanted into germ-free mice, which then began to exhibit symptoms of PD.
Sarkis said; “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.”
Dr Arthur Roach, Director of Research at Parkinson’s UK, said: “In recent years, evidence has been growing that Parkinson’s may begin in the gut but the chain of events involved has so far remained a mystery.
“This work opens an exciting new avenue of study on the gut-brain connection in Parkinson’s. There are still many questions to answer but we hope this will trigger more research that will ultimately revolutionise treatment options for Parkinson’s.”