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New medicine: How the gut breaks the mind

DECCAN CHRONICLE | govind vijaykumar

Published on: December 17, 2016 | Updated on: December 17, 2016

Parkinson’s disease was first discovered in 1817. British pharmacist James Parkinson wrote Shaking Palsy, an essay documenting a total of six cases marked by tremors, loss of posture and muscle strength. But there were clues to this sinister disease much before Mr Parkinson even set out to print his findings. The Egyptians wrote about a "drooling king" and even the Bible has a reference to tremors. Which makes Parkinson’s disease, one of the oldest, unsolved mysteries still haunting the human body.

But a new study by experts at the Californian Institute of Technology claims the key to understanding this degeneration of the brain, lies in the stomach. More specifically, they have formally linked Parkinson’s to abnormalities in the gut. For years, constipation has been the first clue. Researchers noticed that people suffering from Parkinson’s had reported constipation at least 10 years before the onset of characteristic tremors. These studies went on to suggest that causes and symptoms of PD were not limited to the human head.

But the Caltech research has for the first time proven the existence gut-brain link. And they used mice. Lead researcher Sarkis Mazmanian and his team showed how tweaking with gut bacteria allowed them to "trigger" the disease in the mice. Much of this three-part study revolves around a protein called alpha-synuclein. The cells in a human brain die off due to an accumulation of this protein — which is when PD sets in.

The mice used in the study were genetically modified to over-produce alpha-synuclein and the only difference between the two sets of rodents was this — one set had no gut bacteria and the other had a full environment in their intestines. The mice lacking bacteria were functioning normally until they were injected with certain chemicals that are commonly manufactured by gut bacteria. The test was to determine if even the germ-free mice would show symptoms if gut bacteria activity was triggered in them. And they did.

In the third test, they injected samples of gut bacteria from human patients of Parkinson’s into the germ-free mice. And soon, the mice started exhibiting symptoms of the disease, proving that anomalies in the gut were directly responsible for brain damage. "What this tells you is that it is not the presence or absence of bacteria that matters, it is the types of bacteria that are there," Mazmanian was quoted as saying.

The discovery is the first big step towards tracing the origins of Parkinson’s disease. The results can lead to development of next-generation probiotics which can not just cure, but prevent the disease in humans. Because we now know that chemicals in the gut can be the direct triggers of neurological breakdowns.

"This was the ‘eureka’ moment, the mice were genetically identical, the only difference was the presence or absence of gut microbiota. Now we were quite confident that gut bacteria regulate, and are even required for, the symptoms of Parkinson’s disease," Timothy Sampson, who was part of the team, said.

The experiment is game-changing because we finally have new targets in the fight against Parkinson’s. And the gut-brain link widens the brief for the development of new drugs. We don’t have to aim for just the head, anymore.