Very interesting results published last week regarding the bacteria in the intestinal system of people with Parkinson’s disease.
This is an important piece of research because the gut is increasingly being seen as one of the potential start sites for Parkinson’s disease.
In today’s post we will review the results and discuss what they mean.
Bacteria in the gut. Source: Huffington Post
Before you go to bed tonight, contemplate this:
The human gut hosts tens of trillions of microorganisms, including at least 1000 species of bacteria (which is a guess-timate as we are not really sure how many species there are).
And whenever you feel like you are all alone, know that you are not.
You are never alone: tens of trillions of microorganisms are with you!
And there is sooooooo many of these microorganisms, that they can make up as much as 2 kg of your total weight.
What do the microorganisms do?
Ours bodies are made up of microbiota – that is, collections of microbes or microorganisms inhabiting particular environments (or region of our body) and creating “mini-ecosystems”. And whether you like this idea or not, you need them.
The microorganisms in the human gut, for example, perform all manner of tasks for you to make your life easier. From helping to break down food, to aiding with the production of some vitamins (in particular B and K).
That’s great, but what does the bacteria in our gut have to do with Parkinson’s disease?
People with Parkinson’s disease quite often have issues associated with the gastrointestinal tract (or the gut), such as constipation for example. Some people believe that some of these gut related symptoms may actually pre-date a diagnosis of Parkinson’s disease, which has led many researchers to speculate as to whether the gut could be a starting point for the condition.
Today we re-address this topic because a group of scientists from the USA have determined that the populations of bacteria in the guts of people with Parkinson’s disease are different to those of healthy individuals.
Sounds interesting. What exactly is the difference?
Well, before we discuss that, we need a little bit of background.
In 2015, a group of scientists from Finland, published this research paper:
Title: Gut microbiota are related to Parkinson’s disease and clinical phenotype.
Authors: Scheperjans F, Aho V, Pereira PA, Koskinen K, Paulin L, Pekkonen E, Haapaniemi E, Kaakkola S, Eerola-Rautio J, Pohja M, Kinnunen E, Murros K, Auvinen P.
Journal: Mov Disord. 2015 Mar;30(3):350-8.
In this study the researchers compared the fecal microbiomes of 72 people with Parkinson’s disease and 72 control subjects by sequencing the V1-V3 regions of the bacterial 16S ribosomal RNA gene.
Hang on a minute. What does… any of that mean?
Yeah. Ok, that was a bit technical.
The microbiome refers to the genetics of the microorganisms – that is their genomes (or DNA). When researchers want to look at the microbiome of your gut, they do so by collecting fecal samples (delightful job, huh?).
Interesting facts: Fresh feces is made up of approx. 75% water. Of the remaining solid fraction, 84–93% is organic solids. These organic solids consist of: 25–55% gut bacterial matter, 2–25% protein, 25% carbohydrates, and 2–15% fat (Source: Wikipedia).
Still with me?
After collecting the fecal samples, researchers will extract the DNA from the gut bacterial material, which they can then analyse.
And what are the V1-V3 regions of the bacterial 16S ribosomal RNA gene?
The 16S ribosomal RNA gene is universal in bacteria – it is present in all of their genomes/DNA. The genetic sequence of this particular gene is approximately 1,550 base pairs long, and contains regions that are highly conserved (that is they are shared between species) and highly variable (very different between species).
The 16S ribosomal RNA gene. Source: Alimetrics
The gene contains nine of these highly variable regions (called V1 – V9) that display considerable differences in the genetic sequence between different groupings of bacteria. The V2 and V3 regions are considered the most suitable for distinguishing all bacterial species to the genus level (‘genus‘ being a method of classification).
Now scientist can amplify the 16S ribosomal RNA gene by making lots of copies of the highly conserved regions (using PCR) which are shared between bacteria, but then they will genetic sequence the variable sections in between (in this case V2 & V3), which will allow them to discriminate and quantify the different species of microorganisms (such as bacteria) within a particular sample.
16S rRNA gene analysis – looks complicated. Source: Slideshare
And this is what the scientists in this study did.
They took fecal samples of 72 people with Parkinson’s disease and 72 control subjects, amplified the V1-V3 regions of the bacterial 16S ribosomal RNA gene, and then sequenced the variables regions in between to determine what sorts of bacteria were present (and/or different) in the guts of people with Parkinson’s disease.
The researchers found that there was a reduced abundance of Prevotellaceae in the guts of people with Parkinson’s disease (Prevotellaceae are commonly found in the gastric system of people who maintain a diet low in animal fats and high in carbohydrates, for example vegetarians).
Prevotella multisaccharivorax which belongs to the Prevotellaceae family. Source: MindsofMalady
In addition, the investigators also reported a positive association between the abundance of Enterobacteriaceae and postural instability and gait difficulty symptoms – that is to say, people with Parkinson’s disease who also had postural instability and gait difficulties had significantly more Enterobacteriaceae in their guts than people with Parkinson’s disease who were more tremor dominant.
Due to the design of the study, the researchers were not able to make conclusions about causality from their study. Neither could they tell whether the microbiome changes were present before the onset of Parkinson’s disease or whether they simply developed afterwards. All they could really say was at the time of analysis, they did see a difference in the gut microbiota between people with and without Parkinson’s disease.
And while these same researchers are currently conducting a two year follow up study to determine the stability of these differences over time in the same subjects, they admit that much larger prospective studies are required to address such issues as causality.
Which brings us to the new research published last week:
Title: Parkinson’s disease and Parkinson’s disease medications have distinct signatures of the gut microbiome.
Authors: Hill-Burns EM, Debelius JW, Morton JT, Wissemann WT, Lewis MR, Wallen ZD, Peddada SD, Factor SA, Molho E, Zabetian CP, Knight R, Payami H.
Journal: Mov Disord. 2017 Feb 14. [Epub ahead of print]
The researchers in this study (completely independent from the previous study) applied the same study design as the previous study, but on a much larger scale:
They took samples from a total of 197 people with Parkinson’s disease and 130 healthy controls. And importantly, none of the individual subjects in the study were related (this was an attempt to reduce the effect of shared microbiota between people who live together). Participants were enrolled from the NeuroGenetics Research Consortium in the cities of Seattle (Washington), Atlanta (Georgia) and Albany (New York).
So what did they find?
The researcher’s data revealed alterations in at least 7 families of bacteria: Bifidobacteriaceae, Christensenellaceae, Tissierellaceae, Lachnospiraceae, Lactobacillaceae, Pasteurellaceae, and Verrucomicrobiaceae families
Of particular interest was their observation of reduced levels of Lachnospiraceae in Parkinson’s disease subjects. Lachnospiraceae is involved with the production of short chain fatty acids (SCFA) in the gut. Depletion of SCFA has been implicated in the pathogenesis of Parkinson’s disease (Click here for more on this), and it could potentially explain the inflammation and microglial cell activation observed in the brain (Click here for more on this).
Importantly, they did not replicate the association of Parkinson’s disease with Prevotellaceae (see the previous study above).
The investigators also looked at the medication that the subjects were taking and they found a significant difference in the gut microbiome in relation to treatment with COMT inhibitors and anticholinergics. The effects of COMT inhibitors and anticholinergics on hte microbiome was independent of the effect that Parkinson’s disease was having.
The investigators concluded that Parkinson’s disease is accompanied by ‘dysbiosis of gut microbiome’ (that is, microbial imbalance). Again they could not determine whether the ‘chicken came before the egg’ so to speak, but it will be interesting to see what follow up work in this study highlights.
What does it all mean?
The studies that we have reviewed today provide us with evidence that the bacteria in the guts of people with Parkinson’s disease are different to that of healthy control subjects. Whether the differences between the studies results are due to regional effects (Finland vs USA) will require further investigation. But given that so much attention is now focused on the role of the gut in Parkinson’s disease, it is interesting that there are differences in the gut microbiome between people with and without Parkinson’s disease.
One issue that both studies do not address is whether this difference is specific to Parkinson’s disease and not other neurodegenerative conditions. That is to say, it would have been very interesting if the investigators had included a small set of samples from people with Alzheimer’s disease, for example. This would indicate which differences are specific to Parkinson’s disease as opposed to differences that a general to individuals who have a neurodegenerative condition. If they can tease out medication-related differences (in the second study), then this should be a do-able addition to any future studies.
One would also hope that the researchers will go back and dig a little deeper with future analyses. Using 16S ribosomal RNA gene analysis to determine and quantify the different families of bacteria is analogous to dividing people according to hair and eye colour. The bacteria of our gut is a lot more complicated than this review has suggested. For example, future studies and follow up research could include some genetic techniques that go beyond simply sequencing the 16S ribosomal RNA gene. The investigators could sequence the entire genomes of these species of bacteria to see if genetic mutations within a particular family of bacteria is present in people with Parkinson’s disease.
Easy to say of course. A lot of work, in practise.
There is most likely going to be more of a focus on the gastrointestinal tract in Parkinson’s disease research as a result of these studies. It will be interesting to see where this research leads.
The banner for today’s post was sourced from Youtube
In the world of scientific research, if you publish your research in one of the top peer-reviewed journals (eg. Cell, Nature, or Science) that means that it is pretty important stuff.
This week a research report was published in the journal Cell, dealing with the bacteria in our gut and Parkinson’s disease. If it is replicated and confirmed, it will most certainly be considered REALLY ‘important stuff’.
In today’s post we review what the researchers found in their study.
Bacteria in the gut. Source: Huffington Post
Although we may think of ourselves as individuals, we are not.
We are host to billions of microorganisms. Ours bodies are made up of microbiomes – that is, collections of microbes or microorganisms inhabiting particular environments and creating “mini-ecosystems”. Most of these bacteria have very important functions which help to keep us healthy and functioning normally. Without them we would be in big trouble.
One of the most important microbiomes in our body is that of the gut (Click here for a nice short review on this topic). And recently there has been a lot of evidence that the microbiome of our gut may be playing a critical role in Parkinson’s disease.
What does the gut have to do with Parkinson’s disease?
We have previously written about the connections between the gut and Parkinson’s disease (see our very first post, and subsequent posts here, here and here), and there are now many theories that this debilitating condition may actually start in the gastrointestinal system. This week a new study was published which adds to the accumulating evidence.
So what does the new study say?
Title: Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson’s Disease
Authors: Sampson TR, Debelius JW, Thron T, Janssen S, Shastri GG, Ilhan ZE, Challis C, Schretter CE, Rocha S, Gradinaru V, Chesselet MF, Keshavarzian A, Shannon KM, Krajmalnik-Brown R, Wittung-Stafshede P, Knight R, Mazmanian SK
Journal: Cell, 167 (6), 1469–1480
PMID: 27912057 (this article is available here)
The researchers (who have previously conducted a great deal of research on the microbiome of the gut and it’s interactions with the host) used mice that have been genetically engineered to produce abnormal amounts of alpha synuclein – the protein associated with Parkinson’s disease (Click here for more on this). They tested these mice and normal wild-type mice on some behavioural tasks and found that the alpha-synuclein producing mice performed worse.
A lab mouse. Source: USNews
The researchers then raised a new batch of alpha-synuclein producing mice in a ‘germ free environment’ and tested them on the same behavioural tasks. ‘Germ free environment’ means that the mice have no microorganisms living within them.
And guess what happened:
The germ-free alpha-synuclein producing mice performed as well as on the behavioural task as the normal mice. There was no difference in the performance of the two sets of mice.
How could this be?
This is what the researchers were wondering, so they decided to have a look at the brains of the mice, where they found less aggregation (clustering or clumping together) of alpha synuclein in the brains of germ-free alpha-synuclein producing mice than their ‘germ-full’ alpha-synuclein producing mice.
This result suggested that the microbiome of the gut may be somehow involved with controlling the aggregation of alpha-synuclein in the brain. The researchers also noticed that the microglia – helper cells in the brain – of the germ-free alpha-synuclein producing mice looked different to their counterparts in the germ-full alpha-synuclein producing mice, indicating that in the absence of aggregating alpha synuclein the microglia were not becoming activated (a key feature in the Parkinsonian brain).
The researchers next began administering antibiotics to see if they could replicate the effects that they were seeing in the germ-free mice. Remarkably, alpha-synuclein producing mice injected with antibiotics exhibited very little dysfunction in the motor behaviour tasks, and they closely resembling mice born under germ-free conditions.
How antibiotics work. Source: MLB
Antibiotics kill bacteria via many different mechanisms (eg. disrupting the cell membrane or targeting protein synthesis; see image above), and they have previously demonstrated efficacy in models of Parkinson’s disease. We shall come back to this in a section below.
The researchers in the study next asked if the microbiome of people with Parkinson’s disease could affect the behaviour of their germ free mice. They took samples of gut bacteria from 6 people who were newly diagnosed (and treatment naive) with Parkinson’s disease and from 6 healthy age matched control samples. These samples were then injected into the guts of germ free mice… and guess what happened.
The germ-free mice injected with gut samples from Parkinsonian subjects performed worse on the behavioural tasks than those injected with samples from healthy subjects. This finding suggested that the gut microbiome of people with Parkinson’s disease has the potential to influence vulnerable mice.
Note the wording of that last sentence.
Importantly, the researchers noted that when they attempted this experiment in normal mice they observed no difference in the behaviour of the mice regardless of which gut samples were injected (Parkinsonian or healthy). This suggests that an abundance of alpha synuclein is required for the effect, and that the microbiome of the gut is exacerbating the effect.
So what does it all mean?
If it can be replicated (and there will now be a frenzy of research groups attempting this), it would be a BIG step forward for the field of Parkinson’s disease research. Firstly, it could represent a new and more disease-relevant model of Parkinson’s disease with which drugs can be tested (it should be noted however that very little investigation of the brain was made in this study. For example, we have no idea of what the dopamine system looks like in the affected mice – we hope that this analysis is ongoing and will form the results of a future publication).
The results may also explain the some of the environmental factors that are believed to contribute to Parkinson’s disease. Epidemiological evidence has linked certain pesticide exposure to the incidence Parkinson’s disease, and the condition is associated with agricultural backgrounds (for more on this click here). It is important to reinforce here that the researchers behind this study are very careful in not suggesting that Parkinson’s disease is starting in the gut, merely that the microbiome may be playing a role in the etiology of this condition.
The study may also mean that we should investigate novel treatments focused on the gut rather than the brain. This approach could involve anything from fecal transplants to antibiotics.
EDITORIAL NOTE HERE: While there are one or two anecdotal reports of fecal transplants having beneficial effect in Parkinson’s disease, they are few and far between. There have never been any comprehensive, peer-reviewed preclinical or clinical studies conducted. Such an approach, therefore, should be considered EXTREMELY experimental and not undertaken without seeking independent medical advice. We have mentioned it here only for the purpose of inserting this warning.
Has there been any research into antibiotics in Parkinson’s disease?
You might be surprised to hear this, but ‘Yes there has’. Numerous studies have been conducted. In particular, this one:
Title: Minocycline prevents nigrostriatal dopaminergic neurodegeneration in the MPTP model of Parkinson’s disease.
Author: Du Y, Ma Z, Lin S, Dodel RC, Gao F, Bales KR, Triarhou LC, Chernet E, Perry KW, Nelson DL, Luecke S, Phebus LA, Bymaster FP, Paul SM.
Journal: Proc Natl Acad Sci U S A. 2001 Dec 4;98(25):14669-74.
PMID: 11724929 (This article is OPEN ACCESS if you would like to read it)
In this research study, the researchers gave the antibiotic ‘Minocycline’ to mice in which Parkinson’s disease was being modelled via the injection of a neurotoxin that specifically kills dopamine neurons (called MPTP).
Minocycline is a tetracycline antibiotic that works by inhibiting bacterial protein synthesis. It has also been shown to exert neuroprotective effects in different models of neurodegeneration via several pathways, primarily anti-inflammatory and inhibiting microglial activation.
The researchers found that Minocycline demonstrated neuroprotective properties in cell cultures so they then tested it in mice. When the researchers gave Minocycline to their ‘Parkinsonian’ mice, they found that it inhibited inflammatory activity of glial cells and thus protected the dopamine cells from dying (compared to control mice that did not receive Minocycline).
Have there been any clinical trials of antibiotic?
Again (surprisingly): Yes.
Title: A pilot clinical trial of creatine and minocycline in early Parkinson disease: 18-month results.
Authors: NINDS NET-PD Investigators..
Journal: Clin Neuropharmacol. 2008 May-Jun;31(3):141-50.
PMID: 18520981 (This article is OPEN ACCESS if you would like to read it)
This research report was the follow up of a 12 month clinical study that can be found by clicking here. The researchers had taken two hundred subjects with Parkinson’s disease and randomly sorted them into the three groups: creatine (an over-the-counter nutritional supplement), minocycline, and placebo (control). All of the participants were diagnosed less than 5 years before the start of the study.
At 12 months, both creatine and minocycline were noted as not interfering with the beneficial effects of symptomatic therapy (such as L-dopa), but a worrying trend began with subjects dropping out of the minocycline arm of the study.
At the 18 month time point, approximately 61% creatine-treated subjects had begun to take additional treatments (such as L-dopa) for their symptoms, compared with 62% of the minocycline-treated subjects and 60% placebo-treated subjects. This result suggested that there was no beneficial effect from using either creatine or minocycline in the treatment of Parkinson’s disease, as neither exhibited any greater effect than the placebo.
Was that the only clinical trial?
Another clinical trial, targeted a particular type of gut bacteria: Helicobacter pylori (which we have discussed in a previous post – click here for more on that).
Title: Eradication of Helicobacter pylori infection improves levodopa action, clinical symptoms and quality of life in patients with Parkinson’s disease.
Authors: Hashim H, Azmin S, Razlan H, Yahya NW, Tan HJ, Manaf MR, Ibrahim NM.
Journal: PLoS One. 2014 Nov 20;9(11):e112330.
PMID: 25411976 (This article is OPEN ACCESS if you would like to read it)
In this study, the researchers recruited 82 people with Parkinson’s disease. A total of 27 (32.9%) of those subjects had positive tests for Helicobacter pylori, and those participants had significantly poorer clinical scores compared to Helicobacter pylori-negative subjects. The researcher gave the participants a drug that kills Helicobacter pylori, and then twelve weeks later the researchers found improvements in levodopa onset time and effect duration, as well as better scores in motor performance and quality of life measures.
The researchers concluded that the screening and eradication of Helicobacter pylori is inexpensive and should be recommended for people with Parkinson’s disease, especially those with minimal responses to levodopa. Other experiments suggest that Helicobacter pylori is influencing some people’s response to L-dopa (click here for more on that).
Some concluding thoughts
While we congratulate the authors of the microbiome study published in the journal Cell for an impressive piece of work, we are cautious in approaching the conclusions of the study.
All really good research will open the door to lots of new questions, and the Cell paper published last week has certainly done this. But as we have suggested above, the results need to be independently replicated before we can get to excited about them. So while the media may be making a big fuss about this study, we’ll wait for (and report here) the follow-up, replication studies by independent labs before calling this REALLY ‘important stuff’.
The banner for today’s post was sourced from the Huffington Post
At the Movement Disorders meeting held in Berlin two weeks ago, there was an interesting presentation dealing with a topic close to our hearts (literally).
In a previous post, we have discussed research suggesting that people (Danes) with vagotomies (severing of the nerves from the stomach to the brain) have a reduced risk of Parkinson’s disease – supporting the idea that perhaps the gut is a one site of disease initiation (click here to read that post).
At the meeting in Berlin, however, data was presented that failed to replicate the findings in a separate group of people (Sweds!).
Title: Vagotomy and Parkinson’s disease risk: A Swedish register-based matched cohort study
Authors: B. Liu, F. Fang, N.L. Pedersen, A. Tillander, J.F. Ludvigsson, A. Ekbom, P. Svenningsson, H. Chen, K. Wirdefeldt
Abstract Number: 476 (click here to see the original abstract – OPEN ACCESS)
The Swedish researchers collected information regarding 8,279 individuals born in Sweden between 1880 and 1970 who underwent vagotomy between 1964 and 2010 (3,245 truncal and 5,029 selective). For each vagotomized individual, they collected medical information for 40 control subjects matched for sex and year of birth (at the date of surgery). They found that vagotomy was not associated with Parkinson’s disease risk.
Truncal vagotomy was associated with a lower risk more than five years after the surgery, but that result was not statistically significant. The researcher suggested that the findings needs to be verified in larger samples.
Differences between the studies?
The Danish researcher analysed medical records between 1975 and 1995 from 5339 individuals had a truncal vagotomy and 5870 had superselective vagotomy. The Sweds on the other hand, looked over a longer period (1964 – 2010) but at a smaller sample size (3,245 truncal and 5,029 selective).
We must note here that the current research has not been peer-reviewed and we are presenting it here for interests sake. But it come after a series of correspondence regarding the original Danish paper were published in the journal Annals of Neurology. Those letters to the editor were from a group of researchers (believe it or not, mainly Norwegians) reported that an analysis of the same data sets used in the original study failed to find a significant difference between the groups – that is, no protective effect for vagotomies in Parkinson’s disease.
This Scandinavian debate has important implications for Parkinson’s disease, bringing in to question the idea that Parkinson’s disease may begin in the gut. Recently, there have also been several reports published suggesting that alpha synuclein present in colonic biopsies may not be as useful in diagnosing Parkinson’s disease as previously proposed.
And this is why the path of science is such a long one – interesting new findings need to be replicated before they can be added to our understanding of the world around us. And if those interesting results can not be replicated, then we have to ask ‘why?’
Watch this space.
New Parkinson’s Research this week:
Title: Vagotomy and Subsequent Risk of Parkinson’s Disease.
Authors: Svensson E, Horváth-Puhó E, Thomsen RW, Djurhuus JC, Pedersen L, Borghammer P, Sørensen HT.
Journal: Annals of Neurology, 2015, May 29. doi: 10.1002/ana.24448.
What’s it all about?
This is Prof Heiko Braak:
Source – Memim.com
Many years ago, Prof Braak – a German neuroanatomist – sat down and examined hundreds of postmortem brains from people with Parkinson’s disease.
He had collected brains from people at different stages of Parkinson’s disease and was looking for any kind of pattern that might explain where and how the disease starts. His research led to what is referred to as the Braak stages of Parkinson’s disease – a six step explanation of how the disease spreads up from the brain stem and into the rest of the brain (see Braak et al, 2003).
Braak’s results also led him to propose that Parkinson’s disease may actually begin in the gut and then spread to the central nervous system (the brain). He based this on the observation that many brains that exhibited the very early stages of Parkinson’s disease had disease-related pathology in a population of neurons called the dorsal motor nucleus of the vagal nerve. This population of neurons connects to different organs in the body, such as the lungs, heart, kidneys and the gastrointestinal system (or the gut).
A diagram illustrating the vagal nerve connection with the enteric nervous system which lines the gastric system. Source: Braak et al (2006) Nature Reviews Neurology 8, 329-339
Braak and his colleagues went on to examine the nerves fibres around the gastrointestinal system and in those fibres he found large deposits of a Parkinson’s disease-related substance: a protein called alpha synuclein. These deposits were present even at very early stages of the disease, which supported his theory that maybe the disease was starting in the gut.
This ‘gut to brain’ theory was supported by the fact that people with Parkinson’s disease often complain of gastrointestinal problems (eg. constipation) and some of these issues may predate the onset of other Parkinson’s disease symptoms. In addition, a couple of years ago, a group of scientists in the USA found alpha-synuclein present in bowel biopsies taken from people years before they were actually diagnosed with Parkinson’s disease (that study can be found here).
The ‘gut to brain’ theory received a further boost recently with the publication of a paper by a Danish group, who retrospectively looked at all the people in Denmark that received a vagotomy between 1975 and 1995.
So what’s a vagotomy?
A vagotomy is a surgical procedure in which the vagus nerve are cut. It is typically due to help treat stomach ulcers. A vagotomy can be ‘truncal‘ (in which the main nerve is cut) or ‘superselective’ (in which specific branches of the nerve are cut, which the main nerve is left in tact).
A schematic demonstrating the vagal nerve surrounding the stomach. Image A. indicates a ‘truncal’ vagotomy, where the main vagus nerves are cut above the stomach; while image B. illustrates the ‘superselective’ vagotomy, cutting specific branches of the vagus nerve connecting with the stomach. Source: Score
And what did the Danish scientists find?
The Danish researcher found that between 1975 and 1995, 5339 individuals had a truncal vagotomy and 5870 had superselective vagotomy. Using the Danish National registry (which which stores everyone’s medical information), they then looked for how many of these individuals went on to be diagnosed with Parkinson’s disease. They compared these vagotomy subjects with more than 60,000 randomly-selected, age-matched controls.
They found that subjects who had a superselective vagotomy had the same chance of developing Parkinson’s disease as anyone else in the general public (a hazard ratio (or HR) of 1 or very close to 1). But when they looked at the number of people in the truncal vagotomy group who were later diagnosed with Parkinson’s disease, the risk had dropped by 35%. Further, when they followed up the Truncal group 20 years later, checking to see who had been diagnosed with Parkinson’s in 2012, they found that they rate was half that of both the superselective group and the control group (see table below – HR=0.53). The authors concluded that a truncal vagotomy reduces the risk of developing Parkinson’s disease.
Source: Svensson et al (2015) Annals of Neurology – Table 2.
So what does it all mean?
The study is an extremely novel approach to investigating the ‘gut to brain’ theory of Parkinson’s disease and the authors can be congratulated on some excellent work. It adds further weight to the idea that something is happening in the gut very early in Parkinson’s disease. It suggests that by cutting one of the main nerves connecting to the stomach, the disease is slowed down if not avoided all together. It might also suggest that the disease is slower and strikes earlier than previously thought (given that some people with truncal vagotomies still developed Parkinson’s disease – maybe the condition started before the nerve was cut).
But there are a couple of important details that should be considered about the paper before everyone rushes out to get a vagotomy:
- The number of people that received a truncal vagotomy (total = 5339) who went on develop Parkinson’s disease 20 years later was just 10 (compared with 29 in the superselective group). There may be some individuals who got lost in the system, but the number is still very low and caution should be used before we get too excited about a result based on a low number of subjects. It is important to determine whether this result can be replicated (in other countries).
- The gut may not be the only avenue for the disease. There has also been theories regarding an environmental aspect to the cause of Parkinson’s disease, and there have been studies conducted looking at the nasal/olfactory system of people with Parkinson’s disease to determine if this is another point of entry for the disease (for a recent review on this, see this paper here).
In summary, very interesting study and fascinating result, but please don’t rush to your doctor and ask for your vagus nerve to be cut!