Source: University of Luxembourg.

Parkinson’s disease is an insidious disease: by the time it manifests as the typical motor dysfunctions such as tremors or muscle rigidity, portions of the brain have already been irreversibly destroyed. By this stage, the disease will have often begun already decades earlier. In search of an early portent 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 present their results in the scientific journal Movement Disorders.

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. This is a protein whose exact function remains 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, known as 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 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. And 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,” Paul Wilmes explains. “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.”

Apart from the LCSB researchers, scientists from the Paracelsus-Elena-Klinik in Kassel, the Department of Neurology of Philipps Universität in Marburg, and the Departments of Neurology and Neuropathology of the University Medical Center Göttingen were involved in the study.

Funding: The work was supported by the Luxembourg Rotary Club under its “Espoir en tête” programme, by the Luxembourg National Research Fund (FNR) and the German Research Foundation (DFG).

Source: Thomas Klein – University of Luxembourg
Image Source: NeuroscienceNews.com image is for illustrative purposes only.
Original Research: Abstract for “The nasal and gut microbiome in Parkinson’s disease and idiopathic rapid eye movement sleep behavior disorder” by Anna Heintz-Buschart PhD,
Urvashi Pandey MS, Tamara Wicke, Friederike Sixel-Döring MD, Annette Janzen MD, Elisabeth Sittig-Wiegand SN, Claudia Trenkwalder MD, Wolfgang H. Oertel MD, Brit Mollenhauer MD, and Paul Wilmes PhD in Movement Disorders. Published online August 26 2017 doi:10.1002/mds.27105

Abstract

The nasal and gut microbiome in Parkinson’s disease and idiopathic rapid eye movement sleep behavior disorder

Background

Increasing evidence connects the gut microbiota and the onset and/or phenotype of Parkinson’s disease (PD). Differences in the abundances of specific bacterial taxa have been reported in PD patients. It is, however, unknown whether these differences can be observed in individuals at high risk, for example, with idiopathic rapid eye movement sleep behavior disorder, a prodromal condition of α-synuclein aggregation disorders including PD.

Objectives

To compare microbiota in carefully preserved nasal wash and stool samples of subjects with idiopathic rapid eye movement sleep behavior disorder, manifest PD, and healthy individuals.

Methods

Microbiota of flash-frozen stool and nasal wash samples from 76 PD patients, 21 idiopathic rapid eye movement sleep behavior disorder patients, and 78 healthy controls were assessed by 16S and 18S ribosomal RNA amplicon sequencing. Seventy variables, related to demographics, clinical parameters including nonmotor symptoms, and sample processing, were analyzed in relation to microbiome variability and controlled differential analyses were performed.

Results

Differentially abundant gut microbes, such as Akkermansia, were observed in PD, but no strong differences in nasal microbiota. Eighty percent of the differential gut microbes in PD versus healthy controls showed similar trends in idiopathic rapid eye movement sleep behavior disorder, for example, Anaerotruncus and several Bacteroides spp., and correlated with nonmotor symptoms. Metagenomic sequencing of select samples enabled the reconstruction of genomes of so far uncharacterized differentially abundant organisms.

Conclusion

Our study reveals differential abundances of gut microbial taxa in PD and its prodrome idiopathic rapid eye movement sleep behavior disorder in comparison to the healthy controls, and highlights the potential of metagenomics to identify and characterize microbial taxa, which are enriched or depleted in PD and/or idiopathic rapid eye movement sleep behavior disorder.

“The nasal and gut microbiome in Parkinson’s disease and idiopathic rapid eye movement sleep behavior disorder” by Anna Heintz-Buschart PhD, Urvashi Pandey MS, Tamara Wicke, Friederike Sixel-Döring MD, Annette Janzen MD, Elisabeth Sittig-Wiegand SN, Claudia Trenkwalder MD, Wolfgang H. Oertel MD, Brit Mollenhauer MD, and Paul Wilmes PhD in Movement Disorders. Published online August 26 2017 doi:10.1002/mds.27105