Microbiome signals early Parkinson's

We head to the United States now, where scientists have done much to advance our understanding of Parkinson's disease. In 2016, researchers at the California Institute of Technology published remarkable findings in the journal Cell which suggested that the brain disorder may be caused by bacteria living in the gut. Or, does the disease provoke a change in the bacteria in the gut? The jury is currently out. Emory University’s Tim Sampson is one of the researchers studying this…

Tim - Since the very beginning, when James Parkinson published his first essay on Parkinson's Disease, or the 'Shaking Palsy' as he called it 200 years ago, he noticed that individuals who had tremors also had significant constipation. Since then, the neurologists have noted that individuals who eventually are diagnosed with Parkinson's disease also often had constipation leading up to that point. So there is this notion that something was occurring within the gut for many decades before even an individual was diagnosed.

Chris - And if we drill into that a bit, is it that the same process that is causing the loss of cells in the brain is causing the problem in the gut? Or does the trouble begin in the intestine and then spread brainwards?

Tim - That's still up in the air. I think both options are open. James Parkinson suggested that maybe there was some sort of infectious organism initiating the pathology from the gut, but I think more recently we're seeing evidence that perhaps there are individuals where it could be starting in the brain and descending into the gut. So it possibly is happening both ways.

Chris - When you look at the gut and specifically the microbes in the gut in people with or who are going to get Parkinson's disease, what changes do you see?

Tim - We've seen that, in individuals with Parkinson's disease, there are particular organisms that appear consistently enriched, and then there are some organisms that are consistently decreased. But what makes the organisms that are decreased really interesting is that those happen to be organisms that feed on dietary fibre. So the organisms that are depleted and missing in the microbiome of people who are already diagnosed with PD are those who preferentially have the ability to eat fibre.

Chris - And is that the reason why there's a constipation problem?

Tim - It's possible, but right now that's just an association.

Chris - And can we transmit Parkinson's, then? In the same way that people have demonstrated, you can take the bacteria from intestines of individuals who are say obese and they're different and you can put them into a mouse and you can make an obese mouse. There's something that the microbes are doing that changes metabolism in a certain way. Maybe it liberates more calories from food. Can you take that cross section of microbes from a Parkinson's individual and transmit that pro Parkinson's state?

Tim - We are able to recapitulate some of the Parkinson's attributes in mice when we perform experiments like this, but we are not actually observing loss of those neurons that happen in people with Parkinson's. So there are particular contributing effects that happen; things like inflammation and immune system activation, protein aggregations, when we transplant microbes from people with Parkinson's disease into mice that have no microbiome, but we are not actually able to see yet a direct type of induction of Parkinson's disease in neurodegeneration and neuron loss.

Chris - Is that just because mice don't get Parkinson's disease whereas, in a human who could, if you did that... It would be unethical to do it, but if you did that experiment, perhaps you would?

Tim - I'm not actually sure. I think it's more likely that the reasons why Parkinson's disease might happen are very multifactorial and the microbiome and the metabolites and the different molecules it produces and signals that it gives to us might be contributing in different ways to the risk, but likely are not causative in the way that other infections for cancer, for instance, can be causative.

Chris - And does that mean then that if we rebalance the microbiome in people who show these pro Parkinsonian changes, that we can affect the trajectory of the disease?

Tim - The microbiome that is in people with Parkinson's disease is very disruptive and it has the ability to signal this more inflammatory tone, this more dysregulated, metabolic way. Balancing that back, I think, could have significant effects on gastrointestinal health and simply on quality of life. There are some emerging studies, one of which is published that has demonstrated some efficacy of a fecal transplant in people with Parkinson's disease over a short term. It's not that it's able to rescue and completely prevent the disease, but it may be able to limit the deficits that happen.