Does Parkinson’s disease originate outside the brain? FNR ATTRACT Fellow leads study suggesting gut bacteria could play a role

 

By the time Parkinson’s disease manifests in symptoms such as tremors, parts of the brain have already been damaged beyond repair. In a quest to shed light on the early stages of the disease, a team of researchers led by FNR ATTRACT Fellow Prof Paul Wilmes, has discovered that the gut of Parkinson’s patients differs from that of healthy people – even at early stages of the disease.

Parkinson’s disease is the second most common neurodegenerative brain disorder, with an estimated 7 to 10 million people affected worldwide. In Luxembourg alone, it is estimated that around 1,000 people are living with the disorder. Currently mostly diagnosed based on motor symptoms assessed during clinical tests, the exact causes still remain unknown.

In search of an early indication of the disease, researchers led by Prof Paul Wilmes, head of the Eco-Systems Biology Group at the Luxembourg Centre for Systems Biomedicine (LCSB) of the University of Luxembourg, may now have found one in the gut: they have shown that the bacterial community in the gut of Parkinson’s patients differs from that of healthy people – even at a very early stage of the disease. The researchers in September 2017 published their results in the scientific journal ‘Movement Disorders’.

Invasion through nose or gastrointestinal tract?

The notion that Parkinson’s originates far outside the brain has been a long-discussed one among experts. The ‘dual hit’ hypotheses sets out that a previously unknown pathogen invades the body in two ways: though the nose or gastrointestinal tract.

Once there, it sets a pathological process in motion, above all the misfolding of a protein of which the function remains unknown (alpha-synuclein). Among other things, this protein is presumed to be involved in the excretion of messengers such as dopamine. The misfolding of this protein could propagate through the nerve pathways, where – decades later – it produces reactions characteristic of Parkinson’s. Ultimately, nerve cells start to die off and the typical symptoms of Parkinson’s disease appear.

Possible new starting point for early treatment

The researchers led by Wilmes, together with physicians Prof Brit Mollenhauer and Prof Wolfgang Oertel and their teams in Göttingen, Kassel and Marburg, explored the question of whether the early events in the course of the disease also change the bacterial community – the microbiome – at the two possible ports of entry.

They took samples from the nose and gut of 76 Parkinson’s patients and 78 healthy control people who are taking part in a long-term study. They also examined the microbiome of 21 subjects diagnosed with iRBD, Idiopathic Rapid-Eye-Movement Sleep Behaviour Disorder. People with this sleep disorder have a greatly elevated risk of developing Parkinson’s disease later in life.

It turned out that the bacterial community of the gut differed considerably between all three groups. “Parkinson’s patients could be differentiated from healthy controls by their respective gut bacteria,” explains the first author Dr Anna Heintz-Buschart from the Eco-Systems Biology Group.

The majority of the differential bacteria showed similar trends in the iRBD group. For example, certain germs were more prevalent in one group while the count was lower in others. In the samples from the subjects’ nasal cavities, however, the researchers found no such differences. The study also revealed that certain gut microbes are associated with non-motor Parkinson’s symptoms, for example depression.

“We hope that, by comparing the groups, we will learn to better understand the role of the microbiome in the process of the disease and to find out what changes occur and when. This might deliver new starting points for early treatment of the disease. It would also be essential knowledge for one day being able to use the absence or presence of certain bacteria as a biomarker for early detection of the disease.” – Paul Wilmes

Link to NCER-PD

The discovery of this ongoing study greatly complements the work carried out by the National Centre for Excellence in Parkinson’s Disease (NCER-PD), funded by FNR. This study is supported by the FNR, via a grant from the FNR’s CORE programme (FNR), by the Luxembourg Rotary Club under its ‘Espoir en tête’ programme, and the German Research Foundation (DFG).

Publication

Anna Heintz-Buschart, Paul Wilmes et al. The nasal and gut microbiome in Parkinson’s disease and idiopathic rapid eye movement sleep behaviour disorder; in: Movement disorders: official journal of the Movement Disorder Society; DOI: 10.1002/mds.27105ghh

Prof Dr Paul Wilmes, FNR ATTRACT Fellow, LCSB at the University of Luxembourg

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