A lay summary by Tia Parker, reviewed by Prof Heather Mortiboys, Dr Scott Allen and a Parkinson’s disease lay panel
Background:
People with Parkinson’s Disease experience a progressive loss of neurons (the main cells of the brain) that produce the chemical messenger dopamine – this messenger is very important for the brain’s ability to control movement and generally function healthily. A large reason for the loss of these neurons is the build-up and clustering of a protein called alpha-synuclein. When there are normal levels of alpha-synuclein, they do not cause harm, however when they cluster together it is thought that they then become harmful and toxic. These harmful clusters are thought to contribute to the worsening of Parkinson’s Disease related damage (pathology) in the brain as they are passed throughout neurons and result in disrupted self-regulation and cell death.
In our gut we have different types of bacteria which can majorly affect our health and how our body functions. There is good bacteria and bad bacteria, which would typically be in balance to avoid any health issues. Researchers have found that when there is an imbalance of these bad bacteria, especially those that are associated with inflammation, this can contribute to Parkinson’s Disease pathology and can therefore be a therapeutic target.
Why is the study important?
The study highlights the importance of how the gut may contribute to neurodegeneration which can be further investigated. Researchers provide evidence that using human umbilical cord blood as a therapeutic approach can be potentially beneficial for those with Parkinson’s disease. With further research, people with early-stage Parkinson’s Disease may be able to start exploring approaches to maintain bacterial balance within their digestive tract by considering what they consume and its impact on their gut. Different diets and supplements can alter the bacterial profile of the gut, therefore, researching and designing diets that reduce inflammation related bacteria would be useful. Though this would not cure them, it may prove useful in managing disease and with further research, potentially even slowing progression.
What did the authors do and how did they do it?
Used one of two treatments in mice:
-
human umbilical cord blood (hUCB) plasma*
-
human umbilical cord blood (hUCB) plasma* and stem cells.
** Plasma is the liquid portion of blood
Mice were either genetically modified to have higher levels of the PD causing protein alpha-synuclein (PD model) or genetically unmodified (control). Researchers used behavioural tests, brain and gut tissue collection from experimental mice and investigated protein levels to assess pathology.
Additionally, researchers cultured human brain cells exposed to homogenised gut (containing microbiota) from control or PD model mice. Cells were analysed for survival and inflammatory response.
What are the results?
Researchers found that there is a pathogenic link between a bacterial imbalance within the gut and degeneration of dopamine producing neurons in the brain. Treating the gut bacteria imbalance via stem cell therapy may contribute to identifying disease-modifying treatment for PD.
Behavioural analysis and gut functional assay results:
Compared to the wild-type mice, the PD model mice showed poor movement ability and gut function. These deficits were improved with treatment of both hUCB plasma and hUCB plasma and stem cells.
Gut microbiome analysis results:
Researchers used techniques to identify specific inflammation associated bacteria within the faeces of the animals used in the study.
There were higher levels of all 3 inflammatory bacteria in the PD model mice compared to the control. Treatment with both hUCB plasma and hUCB plasma and stem cells was found to reduce numbers of these bacteria present when compared to the control mice.
Researchers also found that hUCB plasma and hUCB plasma and stem cell treatments reduced the clumping of the disease protein alpha-synuclein and loss of brain cells in the PD mice model.
What do the finding mean going forward for people with the disease?
The findings of this paper offer insight into the importance of our gut bacteria and how it affects our central nervous system, particularly in individuals living with PD. The findings support the concept of balance within the gut-brain-axis and how inflammatory microbiomes may predispose PD. Additionally, the results indicate that utilising hUCB plasma and hUCB plasma and stem cells as a therapeutic approach may contribute to reducing the associated inflammation and deficits.
This study can be found at https://pubmed.ncbi.nlm.nih.gov/36153318/
Paper title: Inflammatory gut as a pathologic and therapeutic target in Parkinson’s disease
Author list: Jea-Young Lee, Zhen-Jie Wang, Alexa Moscatello, Chase Kingsbury, Blaise Cozene, Jeffrey Farooq, Madeline Saft, Nadia Sadanandan, Bella Gonzales-Portillo, Henry Zhang, Felipe Esparza Salazar, Alma Rosa Lezama Toledo, Germán Rivera Monroy, Reed Berlet, Cyndy D. Sanberg, Paul R. Sanberg and Cesario V. Borlongan
Publication details including date of publication: Nature: Cell Death Discovery. 24 September 2022. doi: 10.1038/s41420-022-01175-2.