Increasing evidence of links between Parkinson’s and gut bacteria

Parkinson’s disease has been repeatedly associated with problems in the gut microbiome, linked to the brain through the nervous system and also to the build up of alpha-Synuclein which damages dopamine-producing cells. One probiotic, Bacillus subtilis, seems to prevent and even reverse this.

Parkinson’s Disease is the second most common neurodegenerative disease after Alzheimer’s. In the over 65s, almost 3% of people develop Parkinson’s.

Early (prodromal) symptoms of Parkinson’s include gut issues, deposits in the GI tract, constipation, mouth ulcers and poor sleep, REM and declining motor skills.

Causal factors include Helicobacter pylori infection in the stomach, lack of physical activity, low urate level (itself associated with changes to the microbiome), smoking and exposure to environmental toxins.

Over the last 5 years, a number of studies have shown a connection between the Enteric Nervous System (a system of inter-connected neurons in the gut wall), and the Central Nervous System. In this way the gut connects to the brain in a two way street. One line of research has thus been focussed on how the gut bacteria, pathogens and even parasites might affect the ENS, and thus the brain. Your gut microbiome has already been dubbed your second brain by expert researchers in America.

Build-up of alpha-synuclein in Parkinson’s disease 

Caltech (California Institute of Technology) researchers have found a link between impaired motor skills and gut bacteria. Apparently, in mice which had certain gut bacteria present and which also overproduced a protein (alpha-synuclein or aSyn), the mice experienced deteriorated motor skills, exactly as those found in Parkinson’s disease. However, in situations where mice overproduced aSyn but did not have the gut bacteria present, there was no loss of motor skills. Clearly then somehow a loss of key gut bacteria may be a cause of Parkinson’s. The results were published in the December 1^st 2016 Issue of ‘Cell’.

Sarkis Mazmanian, Caltech Professor of Microbiology and Heritage Medical Research Institute investigator, said that they need to check the data but, if confirmed, a plan of attack on Parkinson’s might involve the stomach rather than the brain.

The hypothesis was that a toxin or a pathogen (and possible a simultaneous loss of key bacteria) could start the inflammatory process, linked to alpha-synuclein building up in the ENS leading to inflammation in the brain.

The brain normally contains alpha-Synuclein – it is about 1% of total protein volume in the neutrons (the main cells of the brain).

Subsequent research (for example:1) has shown that clumps of alpha-Synuclein protein do, in fact, build up in the brain, and these toxic proteins damage the dopamine-producing cells leading to motor. The clumps are called ‘Lewy bodies’ and they are at their highest levels where there is most damage.

There is now a lot of research looking at how and why there are ‘mutations’ in the alpha-Synuclein in the brain Lewy bodies. Some experts believe this is because they originate in the gut.

Gut bacteria present and missing in Parkinson’s disease

The University of Helsinki has since shown a clear link between certain gut bacteria and Parkinson’s. Their research suggested a loss of Prevotella bacteria but an increase of E. coli in the gut of Parkinson’s patients. They conducted further studies linking antibiotic consumption with Parkinson’s disease.

Go to:  Link between certain gut damage and Parkinson’s

Similar bacterial results were found in a 2020 study (1) from Kiel University, Germany, published in the Annals of Neurology, where analysis of 666 patients’ microbiomes showed people with higher levels of Prevotella were protected from gut problems and motor neurone skill loss, while those with lowered physical activity and more constipation had higher levels of the species Firmicutes. The researchers concluded that “several risk factors and prodromal markers are associated with gut microbiome composition”. They stated that there was a need for more research.

In a June 2020 study, researchers from the State University of New York showed that the Oral Microbiome could be used to predict Parkinson’s disease with an 84.5% accuracy. The bacteria in the mouth inevitably become the bacteria in the gut.

Go to: Oral Microbiome link to Parkinson’s

Could a probiotic reverse or prevent Parkinson’s disease and improve motor skills?

New research(3) from the Universities of Edinburgh and Dundee in Scotland has suggested that a bacterium – Bacillus subtilis – might prevent and even reverse Parkinson’s disease. Using a roundworm model genetically engineered to express human alpha-Synuclein, they found that on feeding the worms the probiotic strain Bacillus subtilis PXN21, the aggregates of A-Syn disappeared. Early days yet!

The probiotic seems to work in three ways – by changing fat metabolism; by increase nitric oxide production (increasing blood flow); by producing biofilms in the gut. Researches also saw changes in dietary restriction and insulin pathways. We recently covered dietary restriction pathways, high dose Resveratrol and Dementia on this Website.

Finally, the use of the probiotic did improve motor skills.

Lead author in the research, Maria Doitsidu, added, “The results an opportunity to investigate how changing the bacteria that make up our microbiome affects Parkinson’s.  The next steps are to confirm these results in mice, followed by fast-tracked clinical trials since the probiotic we tested is already commercially available”.