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Parkinson’s disease researchers shed light into the mysteries of the microbiome

Researchers at the California Institute of Technology have discovered a possible link between gut bacteria in patients with Parkinson’s disease and deterioration of motor skills. A diverse community of beneficial and sometimes harmful bacteria live in the gut and influence the functioning of the immune and nervous systems. The microbiome is communities of microorganisms, including bacteria, fungi, and yeast that live on people, plants, soil, water, and in the atmosphere. Scientists are only recently scratching the surface of how the microbiome influences health.

Seventy percent of all neurons in the peripheral nervous system are in the intestines, and gastrointestinal (GI) problems often precede motor symptoms in patients with Parkinson’s disease. Parkinson’s disease affects one million people in the US and up to 10 million people around the world. Common symptoms include tremors and difficulty walking, and 75 percent of patients have GI abnormalities. The disease is also characterized by the aggregation of a protein called alpha-synuclein within cells in the brain and gut.

To test whether bacteria in the gut may contribute to Parkinson’s disease, the researchers studied mice that overproduce alpha-synuclein and display symptoms of the disease. The researchers compared a group of mice that had complex gut bacteria with a group bred in a sterile environment that lacked the bacteria. The team observed the two groups doing different activities to measure their motor skills. The group lacking the gut bacteria performed significantly better, demonstrating to the team that the gut bacteria regulate symptoms of Parkinson’s disease.

The researchers explained that when gut bacteria break down dietary fiber, they produce short-chain fatty acids, which are molecules that previous research has shown can activate immune responses in the brain. The team hypothesized that an imbalance in these molecules may lead to brain inflammation and other symptoms in Parkinson’s disease. They were able to show that when the bacteria-free mice were fed these fatty acids, immune cells in the brain became activated. Finally, the last step in the study was to obtain fecal samples from patients with Parkinson’s disease and from a control group. When the human microbiome samples were transplanted into the bacteria-free mice, they began to exhibit symptoms and showed higher levels of the short-chain fatty acids in their feces. Transplanted fecal samples from the control group did not trigger Parkinson’s disease symptoms in the mice. This final experiment suggests that changes to the gut microbiome are likely more than just a consequence of Parkinson’s disease.

For patients with Parkinson’s disease, this research may lead to more effective treatments that target the gut. These could be drugs aimed at modulating the short-chain fatty acids or certain probiotics that may reduce symptoms.

Related: Last spring, the White House Office of Science and Technology (OSTP) announced the National Microbiome Initiative (NMI), a collaboration with federal agencies and private-sector stakeholders to advance the understanding of microbiomes. Most of the efforts coming out of the initiative focus on developing new scientific tools for understanding how microbiomes work. Specific projects seek to learn how microbes affect diabetes and multiple sclerosis. Another project is exploring whole-genome sequencing to check if patients harbor antibiotic-resistant superbugs.

Source:
Jo Handelsman, “Announcing the National Microbiome Initiative,” White House blog, May 13, 2016; Timothy R. Sampson et al, “Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson’s disease, Cell, December 1, 2016.

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Author bio

Doug leads Deloitte Consulting LLP’s Life Sciences and Health Care practice. With 24 years of experience, he works closely with multiple top health care organizations on major clinical and enterprise transformation efforts and on large-scale technology implementation projects. Doug has extensive experience in comprehensive quality and patient safety transformations, turnaround and performance improvement in academic medical centers as well as organization/workflow redesign and technology enablement. He has served as the lead on a number of enterprise transformation initiatives with some of Deloitte’s most largest and most complex clients.