Altered Gut Flora Could Indicate Parkinson's

In search of a early-diagnostic biomarker for Parkinson’s disease, researchers have found that specific changes in the gut microbiota could help identify the disease in its early stages, before clinical symptoms appear.

By the time Parkinson's disease manifests as the typical motor dysfunctions such as tremors or muscle rigidity, portions of the brain have already been irreversibly destroyed; the disease will have often begun already decades earlier. In search of an early portent of the disease, researchers led by Paul Wilmes, professor at University of Luxembourg (Esch-sur-Alzette, 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.

Experts have long been discussing the notion that Parkinson's disease originates far outside the brain. According to the "dual hit" hypothesis, a hitherto unknown pathogen intrudes into the body through two ports of entry: the nose or the gastrointestinal tract. Once there, it sets a pathological process in motion, above all the misfolding of the protein alpha-synuclein, whose function is as yet largely unknown. Among other things, it 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 the typical clumping in the dopaminergic cells, Lewy bodies, that are characteristic of Parkinson's. Ultimately, nerve cells start to die off and the typical symptoms of Parkinson's disease appear.

The researchers led by Prof. 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 microbiome at the two likely 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 Idiopathic Rapid-Eye-Movement Sleep Behaviour Disorder (iRBD), because iRBD patients have a greatly elevated risk of developing Parkinson's disease later in life.

The results showed that the gut bacterial community differed considerably between all three groups. "Parkinson's patients could be differentiated from healthy controls by their respective gut bacteria," explained first-author Dr. Anna Heintz-Buschart. And the majority of the differential bacteria showed similar trends in the iRBD group. For example, certain bacterua 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. Certain gut microbes were also 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," Paul Wilmes explained, "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."

The study, by Heintz-Buschart A et al, was published August 26, 2017, in the journal Movement Disorders.

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