Parkinson’s Disease Linked to Gut Microbiome
Scientists have discovered for the first time a functional link between bacteria in the intestines and Parkinson’s disease (PD). The researchers show that changes in the composition of gut bacterial populations–or possibly gut bacteria themselves–are actively contributing to and may even cause the deterioration of motor skills that is the hallmark of this disease.
The work–which has profound implications for the treatment of PD–appears in Cell.
PD affects up to 10 million worldwide, making it the second most common neurodegenerative disease. Characteristic features of PD include symptoms such as tremors and difficulty walking, aggregation of a protein called alpha-synuclein (αSyn) within cells in the brain and gut, and the presence of inflammatory molecules called cytokines within the brain. In addition, 75 percent of people with PD have gastrointestinal (GI) abnormalities, primarily constipation.
To test if bacteria in the gut may contribute to PD, the researchers utilized mice that overproduce αSyn and display symptoms of Parkinson’s. One group of mice had a complex consortium of gut bacteria; the others, called germ-free mice, were bred in a completely sterile environment and thus lacked gut bacteria. The researchers had both groups of mice perform several tasks to measure their motor skills, such as running on treadmills, crossing a beam, and descending from a pole. The germ-free mice performed significantly better than the mice with a complete microbiome.
When gut bacteria break down dietary fiber, they produce molecules called short-chain fatty acids (SCFAs), such as acetate and butyrate. Previous research has shown that these molecules also can activate immune responses in the brain. Thus, the researchers hypothesized that an imbalance in the levels of SCFAs regulates brain inflammation and other symptoms of PD. Indeed, when germ-free mice were fed SCFAs, cells called microglia–which are immune cells residing in the brain–became activated. Such inflammatory processes can cause neurons to malfunction or even die. In fact, germ-free mice fed SCFAs now showed motor disabilities and αSyn aggregation in regions of the brain linked to PD.
In a final set of experiments, the researchers obtained fecal samples from patients with PD and from healthy controls. The human microbiome samples were transplanted into germ-free mice, which then remarkably began to exhibit symptoms of PD. These mice also showed higher levels of SCFAs in their feces. Transplanted fecal samples from healthy individuals, in contrast, did not trigger PD symptoms, unlike mice harboring gut bacteria from PD patients.