Parkinson’s Awareness Month – an update on the Microbiome and PD

April has been designated Parkinson’s Awareness month.  Every year we see a number of new therapeutic announcements and research projects in the month of April.  These announcements can be both exciting and frustrating, because it takes a long time for new research to make it all the way to the clinical treatment phase.  

The microbiome continues to be a keen area of research interest in Parkinson’s disease.  Since the first paper was published connecting PD and the microbiome by Dr. Filip Scheperjans back in December 2014, we have come a long way in our understanding of the impact of the gut microbiome on Parkinson’s.  But there has been no significant progress on microbiome related treatments.  

Earlier this month there was a news article of a team working on an engineered bacteria that could produce dopamine in the gut continuously.  Dopamine treatment is the long standing gold standard treatment for PD.  A few years back researchers from Harvard showed that certain gut bacteria may be “eating your medicine.”  These two pieces of research present the two ends of the spectrum on microbiome complexity and the difficulty of “engineering” a solution that would be effective across the board.  

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The microbiome is a complex ecosystem.  Research indicates that the number of genes encoding different functions in the gut may be as much as 300x more than in the human genome.  Many gut bacteria already produce dopamine and the precursor neurochemicals in the dopamine pathway.  So engineering a new bacteria to do something that many bacteria already do is not likely to solve the problem, especially if the bacteria that eat dopamine are present in your gut.  The organism identified that eats dopamine is Helicobacter pylori (HP).  This bacteria is also associated with ulcers and more recently with a GI disorder called small intestinal bacterial overgrowth (SIBO).  SIBO is a condition where the bowel flora from the colon begin to make their way up the GI tract to the small bowel where they begin to grow and ferment sugars.  SIBO can be detected through a breath test measuring either hydrogen sulfide or methane gas.   Both hydrogen sulfide and methane have some connections to Parkinson’s through the microbiome.  

One of the early organisms identified in both PD and MS is a methanogen called Methanobrevibacter smithii.   While I have not seen research connecting M.smithii to SIBO but this could be a new area of research and possible therapeutics.  Methanogenic bacteria also produce a peptide called methanobactin.  This peptide is a copper binding peptide.  Copper is essential in the proper functioning of all of the enzymes in the mitochondrial respiratory chain.  Copper is also an essential trace element in the management of iron.  There are many decades of research regarding iron overload and oxidation in Parkinson’s.   When copper is bound by these methanobactins is it unable to do the job of managing the movement of iron in and out of tissues and in and out of its oxidized state.  While methanobactin can reduce copper to the Cu+ form which is beneficial to our cells, we can’t access it if it is bound up in this organism.  Methanobactin can also bind zinc and cobalt.  Copper, zinc and cobalt are all important trace metals for the production of vitamins in our gut by lactobacillus species.  If these metals are bound up and chelated then they are not available for the production of these important nutrients.  

HP is a bacterium that presents in many gastrointestinal diseases.  It has been shown to be more prevalent in people with Parkinson’s and as noted above is associated with poor absorption of L-dopa treatment due to the bacterium’s preference for metabolizing “eating” L.dopa.  In some cases, treatment of HP can improve the effectiveness of L.dopa therapy, however, the use of antibiotics is also associated with Parkinson’s disease, making the approach to treatment a bit tricky.  In addition, many neurology clinicians are not familiar with this connection and are not comfortable with the diagnosis and treatment of GI related disorders.   

On the other side of the HP coin, is its potential protective effects against stomach cancer and active tuberculosis.  How are these relevant to PD?  Several years ago research was published indicating that LRRK2, the best studied Parkinson’s associated gene, is a negative regulator of active tuberculosis meaning it may keep Mycobacteria infections in a latent state.  This has been a keen area of interest of mine and put me in touch with Dr. Tom Dow a researcher focused on Mycobacterium avium paratuberculosis and its potential impact on autoimmunity in a number of diseases including Parkinson’s.  Read more of Dr. Dow’s research here.  So both LRRK2 and HP may protect against active infections by Mycobacteria.  Once again, I think this points out the complexity of our immune system and the microbial interactions in our gut.  The immune system is a razors edge.  On one side we find cancer and the other neurological disease.  Ideally, we maintain a balance and walk the tight rope for a healthy life.  

I write this blog, not to discourage the optimism created in the news by these new findings, but to begin to get you think as a systems thinker.  The gut is an ecosystem.  How best to we treat ecosystems and restore damaged areas in our external ecosystems?  Restoration requires more than one simple solution.  First, we have to stop polluting the areas we aim to restore.  This requires a focused effort.  I often write about the food and water and how important it is to our overall health but especially Parkinson’s disease.  There are many good resources for understand how diet, herbicides, pesticides and water quality impact the microbiome and our health.  One of the early pioneers in this area was Dr. William Davis, author of Wheat Belly, Undoctored, and Super Gut.  Making sure that you are eliminating all sources of pesticides and herbicides from your diet is essential to your microbiome health and may potentially impact the course of Parkinson’s disease if you have.  Dr. Laurie Mischley has talked and written extensively about these impacts.  Once you clean up the pollution then you can begin to restore your gut lining which equates to the soil in the your body.  

Using the soil analogy, we know that poor quality soil is “leaky” and cannot retain the important nutrients required to grow healthy plants.  The same is true of a leaky gut.  The cell lining of our GI tract is quite thin and this barrier protects us from toxins entering the blood stream and tissues as well as supports the uptake of nutrients.  When the lining of our gut is leaky it allows the toxins across and disruptions the proper digestion and uptake of nutrients.  

You can read more about these topics in our blogs or for more detailed discussion of Parkinson’s Disease on Martha's Quest.

Martha Carlin, is a Citizen Scientist, systems thinker, wife of Parkinson’s warrior, John Carlin, and founder of The BioCollective, a microbiome company expanding the reach of science.  Since John’s diagnosis in 2002, Martha began learning the science of agriculture, nutrition, environment, infectious disease, Parkinson’s pathology and much more.  In 2014, when the first research was published showing a connection between the gut bacteria and the two phenotypes of Parkinson’s, Martha quit her former career as a business turnaround expert and founded The BioCollective to accelerate the discovery of the impact of gut health on all human health, including Parkinson’s.  Martha was a speaker at the White House 2016 Microbiome Initiative launch, challenging the scientific community to “think in a broader context”.  Her systems thinking background and experience has led to collaborations across the scientific spectrum from neuroscience to engineering to infectious disease.  She is a respected out of the box problem solver in the microbiome field and brings a unique perspective to helping others understand the connections from the soil to the food to our guts and our brains.  

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