Parkinson’s, Fecal Transplant, Probiotics, Prebiotics…No Answers Yet

Yesterday morning, I got a comment on the Biome Buzz’ Facebook page, in response to last week’s post on the microbiome and the basal ganglia, that said, “Could you put it more simply and tell us what to do about it?  This is Facebook remember not a scientific magazine.”  (And there you have it…yet another example of no good deed going unpunished.  I spend time I don’t have writing these posts for free…and, well…I guess you can’t make all of the people happy all of the time!)

Those of you who regularly read this blog know that I am neither a scientist nor a physician.  I am simply an interested individual with a great personal stake in the progress of research into the gut biome.  I am a mother of a son profoundly affected by autism.  I have an autoimmune disease and fibromyalgia.  I have friends and family who are already suffering, some for years, with illnesses ranging from Parkinson’s disease to cancer.  I have already had to watch my grandmother die of dementia.  Yes…I have a very, VERY big personal stake in this research.

What I do not have are the answers.  Then again, neither do the hundreds, if not thousands, of brilliant doctors and scientists around the world who are in the process of trying to figure this all out.

I won’t even bother to comment on the snark in her comment.  Sheesh.

Anyway, on that note – i.e. more questions than answers – I read a little article[i] over the weekend on fecal microbiota transplant and Parkinson’s disease (PD), which you all know, is of particular interest to me, seeing as how I already have 3 friends with it.  This is a great follow up article to that last post on the basal ganglia, which contains the part of the brain wherein PD is centered. According to this article,  all studies done on PD show alterations in the bacterial microbiome, and while there is some variance, there is also a great deal of overlap:  all agree on an increase in Lactobacillacea, Akkermansia, Enterobacteriaceae and Bifidobacterium, and a decrease in Prevotellaceae, Faecalibacterium and Lachnospiraceae.  There are several hypotheses about how these alterations may play a part in the development of the disease.  One example:  because some of these species found at lower levels in the PD gut are producers of short chain fatty acids (SCFAs), there is a belief that the subsequent decreased levels of SFCAs lead to an increase in inflammation in the PD gut:  “The fact that faeces from PD patients contain lower amounts of SCFA and have increased levels of intestinal inflammation, supports this hypothesis.”

However, as yet, there is no fully cohesive picture:  “The studies do not converge on a specific signature or metabolic pathway for PD…”  What makes this an even more confusing picture is that other neurological and neurodevelopmental disorders, like Alzheimer’s and autism, also show microbiome variability.  What specific microbial profile leads to each specific disease though, since there are many overlaps, is unknown.  (That is, what exact changes lead to Alzheimer’s versus PD?)  More than that, correlation does not prove causality.  We simply do not as yet know definitively if these bacterial differences cause PD.  For example, it is possible that PD causes constipation which, in turn, leads to microbiome alterations.  We also do not, as yet, know if the changes found in those with PD are simply the result of the dopamine medications those affected need to take.  And of course, there is also the bee-in-my-bonnet issue:  none of the current studies looked at any other gut resident other than bacteria.  As yet, there’s no real research into possible alterations in the other members of the microbiota:  fungi, archaea, viruses, let alone the macrobiotic organisms.

I’ve written before, many times, about fecal microbiota transplant and the promise it holds for the treatment of a huge variety of illnesses.  In spite of the ever-growing evidence of a relationship between bacterial microbiome alterations and PD, there are zero clinical studies looking to see if FMT might help.  Apparently, as of today, there is 1 case study in the medical literature:  “…a recent Chinese case study on a PD patient with severe constipation. The constipation as well as his PD symptoms greatly improved after FMT.”  (It just makes you want to scream sometimes, doesn’t it?)  The only good news I can offer is that right now, finally, a human study IS being conducted at a Belgian university, and is scheduled to be completed by the end of this year.  It includes 40 PD patients who will be followed for a year, with checkups every 3 months.

There are animal studies, however:  “These studies mimic the FMT procedure with arguably successful results for the model PD mice, indicating that FMT might work in humans in spite of our incomplete insight in its specific mechanisms.”  It is also significant that giving patients with PD probiotics (Lactobacillus and Bifidobacterium) over 4-12 weeks has “..repeatedly proven to be effective in treating constipation,” and one of these studies assessed motor issues as well:  “…Patients being treated with probiotics showed an improved motor score compared to placebo-treated patients, as well as a reduction of clinical signs of inflammation and oxidative stress compared to placebo-treated patients.”  Unfortunately, this study was hugely flawed in that patients were only assessed after treatment, not before, so there’s no real way of knowing what kind of improvements were actually made, if any.  There have been no trials of prebiotics in PD.  One animal study showed that giving the short-chain fatty acid, butyrate, did lead to an improvement in PD symptoms.  Apparently, though, another paper showed that, again in a rodent model, the introduction of SCFA worsened neuroinflammation in PD.  So the picture is murky, at best.

The authors of this paper discuss in detail why people with PD should not rush to try FMT and why their medical practitioners should exercise great caution at this time:  we don’t know which patients may respond, we don’t know at what stage of PD it may be too late to respond, we don’t know the optimal procedures for making FMT a success due to lack of clinical trials, we don’t even yet know if dysbiosis is directly related to the development of PD.  They conclude that while FMT does hold promise for the eventual treatment of PD, “We think that it would be better to wait for the results of the ongoing trials, in order to shape future protocols, instead of performing new trials without good evidence how to design  these. FMT at this moment is a black box with too many unanswered questions.”  And there is not yet any definitive data on using pro- or prebiotics to help treat the illness.

So back to my disgruntled Facebook reader:  I am sorry that I don’t provide you with non-existent answers.  I can only report the science, and hope, over time, that it provides us with those answers for which we are all anxiously waiting.

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[i] Van Laar, T, Boertien, JM, Herranz, AH. Faecal transplantation, pro- and prebiotics in Parkinson’s Disease; Hope or Hype?  Journal of Parkinson’s Disease. doi.org/10.3233/JPD-191802.