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Gut Bacteria Linked to Parkinsonís Symptoms

In studies with mice, researchers have found that changes in the microbiome — the bacteria living in the gut — may set off the symptoms of Parkinson’s disease (PD). The results, published in the December 1 edition of Cell, suggest a new approach to PD therapies aimed at balancing the microbiome.

The bacteria living in a person’s gut affect much more than digestion — they also play a role in the proper functioning of the immune system. In addition, recent research has shown that people with PD have a different mix of bacteria living in the gut than healthy individuals. Knowing this, and also considering that nerve cells in the gut connect directly to the central nervous system and brain, researchers at the California Institute of Technology set out to investigate links between gut bacteria, inflammation and the brain.

Led by Sarkis K. Mazmanian, Ph.D., the scientists studied a mouse model of PD. The mice were genetically engineered to produce extra alpha-synuclein protein, which forms toxic clumps in the brain cells of people with PD. To test whether gut bacteria might have a role in PD, scientists eliminated bacteria from the mice. They raised some of the mice in a germ-free environment (the mice had no microbes at all in their guts) or treated the mice with antibiotics. Other mice were raised normally and had the usual range of microbes in their gut. Researchers measured their motor skills as they ran on treadmills and walked across a beam.

They fed some of the mice a type of fatty acid made by gut bacteria known as short chain fatty acid (SCFA). SCFAs have recently been shown to activate immune cells in the brain that can potentially damage brain cells. Finally, the researchers obtained fecal samples containing gut bacteria from people with PD and from healthy individuals and transplanted the samples into germ-free mice.

Results

  • All of the mice were genetically identical, and predisposed to develop PD symptoms. But the germ-free mice and mice treated with antibiotics performed better on tests of motor skills, suggesting that gut bacteria were linked to motor difficulties.
  • Feeding SCFAs to germ-free mice triggered inflammation in the brain. These mice also developed PD-like movement symptoms.
  • When fecal samples containing gut bacteria from people with PD were transplanted into germ-free mice, the mice developed PD symptoms. When fecal samples from healthy individuals were transplanted into germ-free mice, there was no effect.

What Does It Mean?

This study demonstrated that gut bacteria can negatively affect the brains of the mice and trigger PD motor symptoms. They also found that the mix of microbes found in the gut of people with PD can also trigger motor symptoms in these PD-prone mice. The scientists also believe that chemical signals from microbes in the gut (SCFAs) were required for the PD symptoms to develop in these mice. The major limitation of the study is that mice with genetic alterations in alpha-synuclein do not demonstrate the typical PD symptoms, which are present with people with the exact same mutations. The study however highlights the potential importance of the gut and gut bacteria in the development and progression of PD.

This study sets the stage for identifying specific microbes that are either harmful or beneficial by their presence — or by their absence – in people with PD as well as understanding how exactly, if at all, bacteria may play a role in the start and progression of PD.

Further studies may also focus on the interaction between the microbiome and genetics, as well as diet or other potential environmental risk factors for PD. For instance, many people with PD report years of constipation before onset of PD. It is unknown if constipation is a sign of PD, which develops before the motor symptoms start, or if constipation is possibly a cause of PD, altering the bacteria in the gastrointestinal tract in a way which may increase PD risk.

Learn More

Do you have additional questions about constipation in PD? We invite readers to learn more by accessing PDF's free resources below, or by contacting our National HelpLine at (800) 457-6676 or info@pdf.org.

Reference: Sampson, T. R., Debelius, J. W., Thron, T., Janssen, S., Shastri, G. G., Ilhan, Z. E., et al. (2016). Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson's Disease. Cell, 167(6), 1469–1480.e12. http://doi.org/10.1016/j.cell.2016.11.018

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Source Date: Dec 09 2016