Two New Papers on Parkinson’s: More Connections to the Microbiome

Two new Parkinson’s disease (PD) studies to report to you, both on the involvement of the gut bacteria.  (It amazes me how rapidly the research on this seems to be progressing.)

The first was published in the Annals of Neurology by German researchers.[i]  They were looking for early markers of PD, and yet again, found that differences in the composition of the gut bacteria were reliable predictors of the early symptoms of motor impairment and constipation.  (Constipation is often the first symptom, often starting years before motor symptoms appear and a diagnosis is finally made.)  The study looked at data on 666 patients from a data set collected to look for information on early markers for PD and Alzheimer’s disease.  18 risk and prodromal (which  means early) markers were considered, including levels of physical activity, sex, smoking, age, the presence of constipation, sleep disorders, exposure to chemicals, etc. – and all were found to affect gut bacteria diversity.

Microbiome composition, the abundance of certain species, was linked to constipation, physical activity, REM sleep, smoking and PD motor symptoms.  Interestingly, these researchers found that a family history of PD, depression, loss of smell, urinary and erectile dysfunction were not associated with the gut bacteria.

One of the biggest factors of all, affecting the microbiome:  lower physical activity.  Those who were more sedentary and had constipation had higher levels of Firmicutes (which I mention in my May 2020 PD research update ) in their stool, but those who had higher levels of physical activity had higher levels of Prevotella  and were less likely to have constipation and early motor deficits.[ii]  (If you remember from previous posts, like this one as just one example, Prevotella tends to be associated with higher fiber “non western” diets.)  They write, “Physical inactivity increases the risk of many chronic diseases including PD; conversely, being active may lead to lower prevalence of prodromal PD markers such as constipation.  The effects of inactivity could be related to the processes observed in PD, that is increased colonic inflammation, immune responses, and intestinal barrier permeability.”

The second study came out of the University of Alabama.[iii]  A history fact I learned from the paper that I thought was really interesting:  “In 2003, Heiko Braak proposed that non-inherited forms of PD are caused by a pathogen in the gut. (This is a growing belief, as I also mention in my March 2020 post.)   He hypothesized that the pathogen could pass through the intestinal mucosal barrier and spread to the brain through the nervous system. I never knew who is the first researcher to suggest a gut connection to the development of PD.  And how amazingly accurate was his prediction, as it’s turning out!

These researchers looked at 520 cases of PD in comparison to 300 controls.  They found 3 clusters of bacteria in the PD patients that were abnormal, two of which substantiated the findings of prior research, including confirming that people with PD had “…reduced levels of a cluster that produce short-chain fatty acids.”  You know from my previous posts on this subject (like this one) that those with PD have low levels of butyrate, for example.  They also found a third cluster:  those with PD have elevated levels of 2 kinds of bacteria that metabolize carbohydrates.  They conclude that indeed, just as Dr. Braak predicted 17 years ago, there is a “…significant overabundance of a cluster of opportunistic pathogens in the guts of persons with PD, compared to control subjects.”  Opportunistic pathogens are considered harmless unless they grow excessively and cause infection, which can happen if the immune system is compromised. (The yeast, Candida, is a great example of this.)

I can’t imagine there is any doubt anymore that those with PD have altered bacterial microbiomes.  So many questions remain though:  are these changes causative, or just another symptom of the disease?  If the former, can the biome be manipulated before symptoms become apparent or worsen?  Do we yet have a biome signature that can diagnose someone at risk before the disease develops?  On the bright side, I think we’re getting closer and closer to answering some of these.  After all, look where we are now compared to 17 years ago, when the idea that PD might be related to the gut flora was nothing more than a far-out theory.

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[i] Heinzel, S., Aho, V.T.E., Suenkel, U., von Thaler, A.‐K., Schulte, C., Deuschle, C., Paulin, L., Hantunen, S., Brockmann, K., Eschweiler, G.W., Maetzler, W., Berg, D., Auvinen, P. and Scheperjans, F. (2020), Gut Microbiome Signatures of Risk and Prodromal Markers of Parkinson Disease. Ann Neurol. doi:10.1002/ana.25788

[ii] https://parkinsonsnewstoday.com/2020/06/05/study-links-gut-bacteria-composition-to-several-markers-of-parkinsons/

[iii] https://www.uab.edu/news/research/item/11389-the-parkinson-s-disease-gut-has-an-overabundance-of-opportunistic-pathogens