Link discovered between gut microbes and Parkinson’s disease

Findings could lead to new treatment options.

Researchers have discovered the first biological link between the gut microbiome and Parkinson’s disease in a mouse model, the results appear in a Cell study. Timothy Sampson and Sarkis Mazmanian from the California Institute of Technology raised genetically modified mice with a Parkinson's-like disease. Antibiotic treatment was found to reduce motor deficits and molecular hallmarks of Parkinson's disease. Meanwhile, the transplantation of gut microbes from patients with Parkinson's disease exacerbated symptoms in these mice.

We spoke to the study’s first author Timothy Sampson. 

RG: What motivated this study? Why do you think the role of gut microbes in Parkinson’s is now being investigated?

Timothy Sampson: We have a plethora of microbes within our gut, and we know that these microbes have critical roles in metabolism and immune function. We sought to understand if these effects, particularly on immune function, could be extended to the brain. Parkinson’s disease has a strong immune component, so it was a logical hypothesis that gut microbes may alter immune function in the context of the disease. Additionally, persons with PD often experience gastrointestinal dysfunction before motor symptoms, suggesting that changes to the gut may subsequently alter the disease.

RG: What did you discover?

Sampson:  We found that signals from gut microbes are required for characteristic, Parkinson’s-like symptoms in a mouse model of PD. Furthermore, we found that gut microbes derived from individuals with PD can impart worsened motor function in this mouse model, compared to microbes derived from otherwise healthy individuals.

This research depicts the findings of Sampson et al., who show that signals from gut microbes are required for the neuroinflammatory responses as well as hallmark gastrointestinal and a-synuclein-dependent motor deficits in a model of Parkinson's disease. Credit: Sampson et al./Cell 2016
This research depicts the findings of Sampson et al., who show that signals from gut microbes are required for the neuroinflammatory responses as well as hallmark gastrointestinal and a-synuclein-dependent motor deficits in a model of Parkinson's disease. Credit: Sampson et al./Cell 2016

RG: How did you conduct the study?

Sampson:  We used a mouse model of PD where the animals over-produce a specific protein, alpha-synuclein. This protein forms aggregations, which are thought to be causative in the disease. This mouse was generated in a germ-free system, so that they are born and raised in the absence of all microbes.

We could then measure motor function and pathology in these germ-free animals, compared to animals with a complex population of gut bacteria. We can also use this germ-free model to introduce bacteria derived from humans to understand the functional consequence of different populations of human bacteria.

RG: What does it mean for our understanding of Parkinson’s disease?

Sampson:  Over the past year, there have been a handful of studies showing that persons afflicted with PD have different populations of microbes in their gut. Our study demonstrates that these different populations have functional consequences on the disease. This lays the foundation for understanding microbialy-modulated physiologies that influence the disease.

RG: What new treatment strategies could result from this?

Sampson:  It is exciting to think about identifying particular microbes that may be pathogenic in PD. We could envision blocking their interactions with patients or removing them altogether to potentially dampen the disease process. Alternatively, we may identify microbes that are missing from PD patients compared to healthy controls, which we could introduce as a potential probiotic treatment. However, we are only at the very early stages of identifying these pathways.

RG: How do genetics influence this?

Sampson: There are a small number of genetic markers that correlate with PD. Some have a very high penetrance for disease, while others have a very low penetrance. But together, the known genetics only account for ~10 percent of all PD cases. Our data may indicate that the function of the gut microbiome could interact with certain genetic backgrounds and influence the disease. We do not yet know how genetics, or even more importantly diet, alter the population of gut microbes during PD.

RG: Are you optimistic about the search for the specific types of microbes? How will you do this?

Sampson:  I think it is a very strong hypothesis. We know that certain populations of gut microbes impart different effects on the disease model. Using our current study, in combination with the handful of studies showing that PD patients harbor distinct gut microbe communities, we may be able to correlate the presence of certain species, or the absence of certain species, with disease or disease severity. Leveraging our germ-free model, we can introduce potential candidates very easily to understand the effects of these specific species on PD characteristics in mice.

Featured image of mouse brain structure courtesy of NICHD/I. Williams.