Out of the mouths of babes and sucklings: gut to PD

reposted from

Out of the mouths of babes and sucklings

There is an ongoing debate about where Parkinson’s starts. The most accepted hypothesis of Braak and colleagues suggests that it starts outside the brian, either in the olfactory (smelling) nerve, or potentially in the gut. Some evidence suggested that people who had had surgery to cut the nerve to their stomach to treat stomach ulcers were at lower risk of Parkinson’s, which added weight to the theory that Parkinson’s might ‘ascend’ through the nerves of the gut to the brain. This fits nicely with the theory that changes in the microbiome (the overall ecosystem of bacteria and other microorganisms) in the gut plays a part in Parkinson’s. However, this finding has been disputed by other studies.

A report published this month, continues the story elsewhere in the digestive tract. Using the highly reliable public health records of the Danish health and civil registration scheme, they tried to find a relationship between having a tonsillectomy and future risk of Parkinson’s. They examined ther records of over a million people, including 195,000 who’d had tonsillectomy, primarily in childhood. They found 100 people who developed Parkinson’s from the tonsillectomy group at a rate of 0.31 (true figure in the region of 0.22-0.34) cases of Parkinson’s per 100,000 person-years, and 568 cases of Parkinson’s in the comparison group at 0.27 (true figure in the region of 0.29-0.34) cases of Parkinson’s per 100,000 person-years. There was no significant difference between the two groups. Therefore, there is no evidence of any effect of tonsillectomy on the risk of developing Parkinson’s.

This is an important negative finding, and the editor of Movement Disorders should be congratulated on publishing it. It is notoriously difficult to publish ‘negative’ studies, as they rarely make headlines in the broadsheets (when was the last time you read that X had no effect on Y, compared to the last story you read claiming that your favourite food put you at risk of …) Although they found no evidence of an effect, that still isn’t quite the same of finding evidence of no effect; and so the debate rages on.

RNR

http://onlinelibrary.wiley.com/doi/10.1002/mds.27253/full

Tonsillectomy and Risk of Parkinson’s Disease: A Danish Nationwide Population-Based Study

Svensson E^1,2, Henderson VW^1,3,4, Szépligeti S¹, Stokholm MG⁵, Klug TE⁶, Sørensen HT^1,3, Borghammer P⁵.

ABSTRACT

Background: We hypothesized that tonsillectomy modifies the risk of PD.

Objectives: To test the hypothesis in a nationwide population-based cohort study.

Methods: We used Danish medical registries to construct a cohort of all patients in Denmark with an operation code of tonsillectomy 1980-2010 (n = 195,169) and a matched age and sex general population comparison cohort (n = 975,845). Patients were followed until PD diagnosis, death, censoring, or end of follow-up 30 November 2013. Using Cox regression, we computed hazard ratios for PD and corresponding 95% confidence intervals, adjusting for age and sex by study design, and potential confounders.

Results: We identified 100 and 568 patients diagnosed with PD among the tonsillectomy and general population comparison cohort, respectively, finding similar risks of PD (adjusted hazard ratio = 0.95 [95% confidence interval: 0.76-1.19]; for > 20 years' follow-up (adjusted hazard ratio = 0.96 [95% confidence interval: 0.64-1.41]).

Conclusion: Tonsillectomy is not associated with risk of PD, especially early-onset PD. © 2017 International Parkinson and Movement Disorder Society

reposted from ScienceAlerts

New evidence suggests Parkinson's might start in the gut, not the brain

We might have been wrong about Parkinson's this whole time.

FIONA MACDONALD

5 DEC 2016

A new study adds to a growing body of research that suggests we might have been thinking about Parkinson's disease wrong this whole time.

Instead of being isolated to the brain, new evidence in mice suggests that the condition might actually start in the gut. And it could explain some of the strange coincidences seen in the disease, such as why most Parkinson's patients complain of constipation up to a decade before other symptoms arise.

Parkinson's disease is most commonly associated with tremors, stiffness, and difficulty moving, caused by neurons deep in the brain being killed off.

Although there are treatments to slow the progress of the condition, there's no way to prevent or cure it, and researchers still don't really understand what causes it and how it progresses.

For years, scientists have limited the search for the cause of Parkinson's to the brain, but a growing body of evidence suggests that might be the wrong approach.

Parkinson's might actually originate in the gut before spreading to the brain, it could explain some of the strange links researchers have seen with Parkinson's patients.

Researchers have noticed that people with Parkinson's often report constipation, as well as other digestive problems, up to 10 years before they notice tremors. There's also evidence that people with Parkinson's disease have different gut bacteria to other healthy adults.

Now a new study in mice has shown that the toxic fibres that build up around the nerve cells of Parkinson's patients can influence the nerves in the brain in a matter of weeks.

"We have discovered for the first time a biological link between the gut microbiome and Parkinson's disease," said lead researcher Sarkis Mazmanianfrom the Californian Institute of Technology (Caltech).

"More generally, this research reveals that a neurodegenerative disease may have its origins in the gut, and not only in the brain as had been previously thought."

The team found this out by looking at the spread of toxic fibres made of a substance known as alpha-synuclein.

Alpha-synuclein is small and soluble in healthy nerve cells, but for some reason, in Parkinson's patients, these alpha-synuclein molecules clump together and form fibres that damage the nerves in the brain.

Around a decade ago, researchers began to report that patients who had these fibres in their brains also had them in their gut.

In the latest study, the Caltech team looked at mice that had been genetically modified to be susceptible to Parkinson's disease, by over-producing alpha-synuclein fibres.

These mice were either raised in normal, non-sterile cages, or in a sterile, germ-free environment.

Mice raised in the germ-free cages showed fewer motor deficits, and less toxic fibres in their brains. But mice raised in the non-sterile environment developed Parkinson's symptoms as expected, given their genetic predisposition.

Antibiotic treatment was able to reduce these symptoms in the non-sterile mice, suggesting there was something in their microbiome that was enhancing the symptoms.

Finally, the team injected gut bacteria from human Parkinson's patients into the germ-free mice. They quickly went from showing hardly any symptoms to deteriorating rapidly.

Gut bacteria taken from healthy people didn't have the same effect.

"This was the 'eureka' moment, the mice were genetically identical, the only difference was the presence or absence of gut microbiota," said one of the team, Timothy Sampson.

"Now we were quite confident that gut bacteria regulate, and are even required for, the symptoms of Parkinson's disease."

The scientists think that the gut bacteria might be releasing chemicals that over-activate parts of the brain, leading to damage. 

There's a lot more research to be done before we can say for sure what's going on, but if this research can be verified and replicated, it could change the way we treat the condition forever.

"That would be game-changing," David Burn, from Newcastle University in the UK, who wasn't involved in the study, told Clare Wilson for New Scientist. "There are lots of different mechanisms that could potentially stop the spread."

The team presented their work at the Society for Neuroscience meeting in San Diego last month, and have now published the results in Cell.

It's important to note that mouse studies often don't translate to human health, and we still don't have the full picture of what's going on here - there might be other important factors involved.

Other studies have shown that people exposed to certain pesticides are more likely to get Parkinson's, so the team thinks that maybe these chemicals could be affecting gut bacteria.

The team now want to analyse the gut microbiomes of people with Parkinson's to try to narrow down which microbes seem to be predisposing people to the disease.

If they could identify certain strains, it means scientists could find a way to screen for Parkinson's before symptoms appear and the damage to the brain occurs. It could also help them come up with new treatment options.

"Much like any other drug discovery process, translating this innovative work from mice to humans will take many years," said Mazmanian. "But this is an important first step." 

The research has been published in Cell.