The gut bacteria of people with Parkinsons is different to that of healthy people

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Dr. Filip Scheperjans at Targeting Microbiota Congress 2014

 

Study links Parkinson's disease to gut bacteria 

4/10/2015

Written by Catharine Paddock PhD

Medical News Today         http://www.medicalnewstoday.com/articles/286912.php 2/3

ClubPD Editor: Dr Paddock's summary of this study below is followed by Dr Scheperjans' more detailed report below that. This is a major finding with the potential for profoundly impacting PD research and treatment going forward. Not only does PD exhibit gut bacteria 'profiles', but so do syndromes like autism.

 

A new study finds that compared to healthy controls, people with Parkinson's disease appear to have distinctly different gut bacteria. They have hardly any bacteria from one family and the amount present from another family seems to increase with disease severity. 

The study, led by the University of Helsinki Institute of Biotechnology in Finland, is published in the journal Movement Disorders. It involved 72 patients with Parkinson's disease and an equal number of matched, healthy controls.

More and more studies are discovering the huge influence that our gut bacteria - which vastly outnumber the cells of our body - have on our health: when they get sick, we get sick.
Parkinson's disease is a progressive motor disorder that develops when the brain loses cells that produce dopamine - a chemical that controls reward and pleasure and also regulates movement and emotional responses.  Parkinson's symptoms include trembling, stiffness, slowness of movement and problems with balance and coordination. The disease rarely strikes before the age of 50 and gradually gets worse - to the point where everyday life and self-care becomes very difficult. According to the National Parkinson's Foundation, up to 60,000 new
cases of Parkinson's are diagnosed each year in the US, adding to the 1 million Americans who currently live with the condition. Some clues already exist about the links between Parkinson's and gut problems. For example, as the study authors say in their paper, "gastrointestinal dysfunction, in particular constipation, is an important non-motor symptom" in Parkinson's disease, and "often precedes the onset of motor symptoms by years."  They also mention that recent research shows gut bacteria interact with parts of the nervous system via various pathways, including the enteric nervous system - the so-called "brain in the gut" - and the vagal nerve. 

Highlighting their findings, lead author of the new study, Dr. Filip Scheperjans, a neurologist in the Neurology Clinic of Helsinki University Hospital, says: The team did not find out what an absence of  Prevotellaceae might mean in Parkinson's disease. But they have many questions. For example, does this family of bacteria protect against the disease? Or does the disease wipe them out?  "It's an interesting question which we are trying to answer," says Dr. Sheperjans. Knowing about gut bacteria could help improve prognosis and treatment in Parkinson's
The team also found that levels of another family of bacteria called Enterobacteriaceae appear to be linked to severity of Parkinson's symptoms. They observed patients who had more difficulty with balance and walking tended to have higher levels of these bacteria.
Dr. Sheperjans and his colleagues are already planning further research to explore the connection between Parkinson's disease and gut bacteria. They have begun to re-examine the same group of patients to find out if the differences in gut bacteria are permanent or whether they change as the disease progresses. If they do change with disease progression, this could help doctors give more accurate prognoses. "In addition," Dr. Sheperjans says, "we will have to see if these changes in the bacterial ecosystem are apparent before  the onset of motor symptoms."  And, he adds, they also want to discover the underlying biological mechanism between gut bacteria and Parkinson's disease. They hope eventually that their findings will lead to new tests for Parkinson's and perhaps even new treatments to stop, slow or even prevent the disease by focusing on gut bacteria. Funds from the Michael J. Fox Foundation for Parkinson's Research and the Finnish Parkinson Foundation helped finance the study.

 

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Gut microbiota in Parkinson’s disease

Written on December 27 2014 at 3:58 PM

By Filip Scheperjans

 

 

I participated in the “Targeting microbiota” congress at Pasteur Institute because I considered the topics discussed very interesting and relevant to my research. For me microbiome conferences are still a rather foreign territory, but I very much like to talk to people with a very different view from what I have. And my learning curve in the microbiome field is still quite steep. I personally was fascinated by the reports about segmented filamentous bacteria and their immunological effects.

I am fascinated by the idea that Parkinson’s could be actually originating from the nose or gut as suggested by, for example, Braak’s model (PMID: 12498954, Neurosci Lett 2006;396(1):67-72). The first neurodegenerative changes in Parkinson Disease (PD) are seen in the olfactory bulb and enteric nervous system. Correspondingly, most PD patients suffer from hyposmia and gastrointestinal symptoms, frequently years before motor symptoms evolve. Interestingly those two habitats are where our body gets mostly exposed to environmental agents, including microbes.

Previous attempts to identify microbes related to PD pointed to Helicobacter pylori and small intestinal bacterial overgrowth, but in the end had been somewhat inconclusive. But there possibly was a signal. At the same time I followed how the microbiome field was keeping pace around 2009/2010 with other areas of research fuelled by the development of next generation sequencing techniques. No one in neurology seemed to be interested in gut microbiota at that time. I thought that this could be a new opportunity to revisit the microbe theory in PD utilizing advanced methodology. In 2010 Petri, my co-PI, who is a genetics expert and head of our genomics lab, wrote an article in a Finnish medical journal about the new possibilities that next generation sequencing (NGS) offers for studying microbiota. After reading this article I contacted him and told him about my ideas and he was immediately excited. For both of us this was completely new territory. For me, since I had been doing neither Parkinson’s nor genetics or microbe research before, and for him, because he had not been involved in neurological research. But I guess in retrospect this may have been one key to succeeding in this endeavor since we were not primed by previous dogmas. So in the beginning there was a lot of reading and we set up a plan. We made an application to the Michael J Fox foundation to fund our rather unconventional pilot study.

 

Main challenges and findings

One challenge was that the clinical part of the study needed to be completed within one year based on the contract with the Michael J fox foundation. So we really had a tight schedule. Regarding the scientific part I found it most difficult to figure out how to account for the many confounding factors and clinical variables that were related to our observations. Standard tools for microbiome analysis make it rather simple to compare community structures between two subject groups. However, it must be considered that there can be many other differences between PD patients and controls in addition to the mere fact that the patients have PD (e.g.medications, comorbidities, constipation). It was difficult to figure out how to account for these potential confounders. Since we did not find a ready solution for it we decided that generalized linear models could be useful here.

The fecal microbiome of PD subjects clearly differed from that of matched controls and this difference was independent of the potential confounders that we assessed. The most significant finding was the abundance of bacteria from the Prevotellaceae family was reduced by 78% in PD patients. On more detailed examination it turned out that, in particular, individuals with a high abundance of these bacteria were not present in the PD group. Consequently, a low abundance of Prevotellaceae was 86% sensitive for PD, but rather unspecific. However, by adding only 3 other bacterial families to the model, we were able to increase specificity for PD to 90%. So microbiome analysis performed quite well in distinguishing PD patients from control subjects. Another interesting finding was that, within the PD group, abundance of Enterobacteriaceae bacteria was related to the severity of postural instability and gait difficulty (PIGD). So there was a connection between gut microbiota and the motor symptoms of our patients. Our study is the first to demonstrate alterations of microbiome composition in neurodegenerative disease. With respect to previous research it is interesting to note that reduced abundance of Prevotellaceae has been reported also in children with autism spectrum disorder and type 1 diabetes (PLoS One 2013;8:e68322; PLoS One 2011;6:e25792).The mechanisms behind this association are not well understood, but it has been suggested that these changes could be related to a breakdown of the gut mucosal barrier, at least in diabetics. Recently, an impaired mucosal barrier has also been found in PD patients (Forsyth et al. 2011; PMID: 22145021) so our findings fit very well into this context. The same study also found that in PD patients Escherichia coli bacteria invade the gut mucosa which may be related to local inflammation and oxidative stress. These bacteria belong into the family Enterobacteriaceae that, in our study, was increased in patients with a PIGD phenotype. This group of patients has a worse prognosis than patients with a tremor dominant phenotype. Thus, it is interesting that exactly this group of bacteria came up also in our study using a completely different approach.

 

Towards more clinical investigations

Our findings (Scheperjans et al. 2014) may point to a role of gut microbiota in PD and suggest that microbiome analysis could be useful as a PD biomarker in diagnosing PD. However, due to the case control design of our study we cannot make conclusions about the causality of the observed relationship. Neither can we tell whether microbiome changes have been present before PD onset or whether they developed afterwards.To answer these questions, larger prospective studies are necessary. We are currently conducting a two-year follow-up study on our subjects to study the temporal stability of the observed differences and the connection between gut microbiota and disease progression. Furthermore, we are assessing the mechanisms of microbiome-host interactions in PD and potential effects of diet in this context. The ultimate questions that need to be answered are whether the observed microbiome alterations in PD are present already before disease onset and thus could be involved in PD pathogenesis and indicate disease risk. In particular, we are interested to know whether Prevotellaceae could have a protective or therapeutic role in PD since virtually none of our 72 PD patients showed high levels of these bacteria in feces. One other explanation could be that a decrease of Prevotellaceae is just reflecting breakdown of the gut mucosal barrier, but not causally involved. Nevertheless, it could still be a potential biomarker. Ultimately, of course, we want to study whether treatments modulating gut microbiota could have symptomatic or even disease modifying effects in PD.

 

Reading recommendations

Lucky for us, no previous study has looked at the gut microbiome in Parkinson’s Disease … in addition to the studies cited above, the following can give more insight into this matter: