A study published last week in the journal Cell offers the strongest evidence yet that Parkinson’s disease begins in the gut, not the brain. The findings, which suggest that the disease is triggered by bacteria that live in the human gastrointestinal tract, promise to open a fresh avenue of inquiry into an illness that affects 10 million people worldwide, and has no cure.
Parkinson’s disease is a neurodegenerative disorder marked by a slow but profound loss of motor function and eventual cognitive decline. (Patients' symptoms often begin with mild tremors and difficulty walking, and progress over years to near complete immobility and oftentimes, dementia).
Doctors and scientists believe that the disease is caused by the buildup of a protein called alpha synuclein in the brain. But they have been at a loss as to what, exactly, triggers that buildup in the first place. Genetic causes are thought to account for only a tiny percentage of Parkinson’s cases.
Enter the microbiome—the ecosystem of microorganisms that naturally colonize the human body. (Fun fact: there's ten times as much microbial DNA in the average human gut as there is human DNA; we are made mostly of microbes!) A growing collection of studies, including some done in humans, have suggested a link between the gut microbiome and neurodegenerative diseases like Parkinson’s.
In the past year alone, four separate studies have found that the gut microbiomes of Parkinson's patients differ significantly from those of people without the disease. But that research did not make clear whether those differences were a cause or merely a consequence of illness. "Those findings really emboldened our own work," says Sarkis Mazmanian, the California Institute of Technology scientist who led the current study. "We've tried to take it a step further by teasing out cause and effect."
Here’s a rundown of these newest findings.
Three Experiments
Scientists conducted three experiments on mice that were genetically engineered to overproduce the protein that causes Parkinson’s. Half of those mice had normal gut microbiomes (that is, their stomachs were churning with bacteria); the other half were sterile and microbe-free.
In the first experiment they simply studied these two groups of mice for signs of Parkinson’s disease. They found that while both groups did in fact produce the protein in excess, the mice with microbiomes developed far more symptoms than the sterile mice did.
In the second experiment they fed both groups of mice molecules (fatty-acid chains) that are normally produced by gut bacteria. When given these molecules, the sterile mice began to exhibit Parkinson’s symptoms.
And in the third experiment, they gave sterile mice gut bacteria from either healthy humans or from human Parkinson’s patients. The latter group developed symptoms, but the group given healthy-person bacteria did not.
Taken together, the results suggest that something about the microbiomes of Parkinson's patients may be contributing to, if not causing, the disease.
Exciting Implications
Parkinson’s disease is incurable. Drugs like L-Dopa can help manage the early symptoms, but as the disease progresses those drugs become less and less effective. Scientists have long been searching for something better, but medications that act on the brain are notoriously difficult to develop because they have to be able to cross the blood-brain barrier to work.
If Mazmanian’s hypothesis is correct—if Parkinson’s patients have certain bacteria in their guts that cause the disease, or lack certain bacteria that can prevent it—scientists may be able to develop treatments that act on the gut. Probiotic-like pills that manipulate intestinal flora might mitigate symptoms in patients, or even prevent the disease altogether.
To be clear, such therapies are a long way off. Before scientists can prescribe specific bacteria (or prescribe the evisceration of other bacteria) as a treatment for neurodegeneration, they will have to do two things:
• Prove that the cause-and-effect relationship Mazmanian's team found holds in humans, not just mice.
• Figure out which of the 1,000 or so bacterial species in the average human gut are causing the problem to begin with.
The race is already on to answer these questions. Mazmanian himself has launched a company, Axial Biotherapeutics, that has licensed global rights to technologies based on this premise. But it is likely to be years, if not decades, before we see actual human treatments.
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