Gut reaction

Microscape/Science Photo Library




















WE HAVE been thinking about Parkinson’s disease all wrong. The condition may arise from damage to the gut, not the brain.

If the idea is correct, it opens the door to new ways of treating the disease before symptoms occur. “That would be game-changing,” says David Burn at Newcastle University, UK. “There are lots of different mechanisms that could potentially stop the spread.”

Parkinson’s disease involves the death of neurons deep within the brain, causing tremors, stiffness and difficulty moving. While there are drugs that ease these symptoms, they become less effective as the disease progresses.

One of the hallmarks of the condition is deposits of insoluble fibres of a substance called synuclein. Normally found as small soluble molecules in healthy nerve cells, in people with Parkinson’s, something causes the synuclein molecules to warp into a different shape, making them clump together as fibres.

The first clue that this transition may start outside the brain came about a decade ago, when pathologists reported seeing the distinctive synuclein fibres in nerves of the gut during autopsies – both in people with Parkinson’s and in those without symptoms but who had the fibres in their brain. They suggested the trigger was some unknown microbe or toxin.

“Knowing the location of the first strike allows for early detection – and treatment”


The finding made sense because people with Parkinson’s often report digestive problems – mainly constipation – starting up to 10 years before they notice tremors. Interestingly, another early symptom of Parkinson’s is a loss of smell. It may be no coincidence, says Burn, that the nose and gut are two organs where nerve cells are exposed to the outside world – and to potentially problematic toxins and microbes.

Now, the synuclein fibres have been shown travelling from the gut to deep within the brain. Collin Challis at the California Institute of Technology and his colleagues injected synuclein fibres into the stomach and intestine of mice. Three weeks later the fibres could be seen at the base of the brain, and by two months they had travelled to parts of the brain that control movement. The mice also became less agile – similar to people with Parkinson’s disease. The work was reported at the Society for Neuroscience meeting in San Diego last month.

This study builds on a growing body of work that the gut plays a role in Parkinson’s, says Burn. For example, people who have had the main nerve to their stomach cut – an old treatment for stomach ulcers – have a lower risk of the condition.

No single bacterium or virus has been pinpointed as the cause. But early evidence suggests that people with Parkinson’s have different gut bacteria to healthy people. Some doctors are already experimenting with treating patients with antibiotics or faecal transplants.

“It could be that having the wrong bacteria in your gut triggers inflammation,” says Sébastien Paillusson at King’s College London. “We know that inflammation makes synuclein more likely to aggregate.”

Other studies have shown that farmers exposed to certain pesticides, and people who get their drinking water from wells – which might be contaminated with pesticides – are more likely to get Parkinson’s. Perhaps these chemicals can also damage nerves in the gut.

Whatever the culprit, knowing the location of the first strike allows for early detection – and treatment. For instance, drugs that mop up synuclein fibres or block their formation are in the works. If these are given to people before the fibres reach the brain they should have a better chance of success. It might also be possible one day to screen for fibers in the nerves of the gut during colonoscopies for early-stage cancers, says Burn.