thescientist | Many people with Parkinson’s disease have digestive symptoms like constipation years before they have neurological symptoms, and scientists have found differences in the gut microbiome compositions of patients with Parkinson’s disease and healthy controls. But whether and how gut microbes contribute to the pathology and symptoms of the disease has been an open question.
In a study published today (December 1) in Cell, a team led by Timothy Sampson and Sarkis Mazmanian of Caltech demonstrate that gut microbiota promote neuroinflammation and motor deficits in a mouse model of Parkinson’s disease. The researchers also identify a possible mechanism for the influence of intestinal microbes and on the development of the disease in mice.
“It’s a beautiful study,” Justin Sonnenburg of Stanford University School of Medicine, who did not participate in the work, told The Scientist. “It’s really a first in establishing that gut microbes can not only contribute, but appear to play a causal role in neurodegenerative disease in this mouse model,” he added.
Sampson, Mazmanian, and colleagues used transgenic mice that overexpress human α-synuclein, the protein that forms the insoluble aggregates that are a hallmark of Parkinson’s disease. These mice exhibit deficits in motor function and gut motility.
Transgenic animals raised germ-free or treated with antibiotics performed better at motor tasks and maintained fecal output, as compared to those with typical microbiota, the researchers reported. Mice without intestinal microbes or those receiving antibiotic treatment also developed fewer α-synuclein aggregates in their brains than did their counterparts with intestinal microbes. In other words, in transgenic mice without intestinal bacteria and in those treated with antibiotics, both Parkinson’s-like symptoms and brain pathology decreased.