The U.S. Army Medical Research and Materiel Command has awarded a four-year, $2.5 million grant to a team of scientists at the University of Alabama at Birmingham (UAB) to investigate the role of the gut microbiome — the trillions of microorganisms and their genetic material that live in the intestinal tract — in Parkinson’s disease.
A goal is to determine if changes made to bacteria in the intestinal tract might help to alter, and possibly interrupt, disease progression.
“Large patient studies have searched for genetic variations and environmental triggers shared by people who have Parkinson’s disease,” Haydeh Payami, PhD, professor in the UAB School of Medicine Department of Neurology, said in a university news release written by Matt Windsor.
“Dozens of genetic risk factors have been identified, but each only increases risk by a small amount,” Payami added. ” There is a significant link between exposure to pesticides and herbicides, as well as repeated head trauma … but again, not all people who have a genetic susceptibility and are exposed to these factors get the disease. There has to be something more than genes and environment.”
Researchers want to identify the specific microorganisms that contribute to disease development; pinpoint bacteria that interact with known genetic risk factors for Parkinson’s; evaluate the effects of two neuroprotective factors — cigarette smoking and caffeine consumption — on the microbiome; search for early microbial changes in patients with REM sleep behavior disorder — a disorder marked by people acting out vivid, often violent dreams, and one that appears to be linked to Parkinson’s; and to study the interaction between gut microbiome and illness progression in animal models of Parkinson’s disease.
Investigators plan to enroll 1,000 Parkinson’s patients and 600 healthy individuals from UAB and the other members of the NeuroGenetics Research Consortium — one of the largest datasets of Parkinson’s patient information — including Emory University, Oregon Health and Science University, the University of Washington in Seattle, and Albany Medical Center in New York.
Another 100 people be treated for REM sleep behavior disorder at UAB and in Montreal, Canada, will also be recruited.
“Eighty percent of people with REM sleep behavior disorder go on to be diagnosed with Parkinson’s or another neurodegenerative disease,” Payami said. “If we can see changes in the microbiomes of these patients decades before they develop Parkinson’s, we could take action. That’s what’s exciting.”
Studies have found that the gut microbiome is altered in Parkinson’s disease. In an experiment, CalTech scientists removed the community of microorganisms found in the intestines of a mouse model of Parkinson’s, and found motor symptoms eased. When they next transplanted bacteria from Parkinson’s patients into these mice, the symptoms returned.
Payami and her team analyzed fecal samples from 197 Parkinson’s patients plus 130 controls from Seattle, New York and Atlanta, and found that the types of microorganisms in the guts of patients was significantly different from those of healthy individuals. Interestingly, they varied according to the person’s geographic site — which may reflect the contribution of environmental, lifestyle, and dietary factors in that person’s biological system. They also reported that Parkinson’s disease medications were associated with changes in the gut microbiome.
“The microbiome metabolizes drugs,” Payami said. “It can turn harmless drugs toxic, and vice versa. Exposure to pesticides and insecticides may be mediated by the microbiome as well. And because the microbiome is easily modifiable, it could offer a way to predict, prevent and even treat Parkinson’s disease.”
Studies have also shown that levodopa’s effectiveness was increased after eradicating a Helicobacter pylori infection in the gut of Parkinson’s patients. In addition, cutting the vagus nerve – the nerve that enables communication between the microbiota, the gut, and the brain – lowered the risk of developing Parkinson’s, adding to microbiome’s potential role in disease onset.
Whether the gut flora is altered because of the disease, if it contributes to the disease process itself, whether the composition of a patient’s intestinal bacteria influences his or her response to treatment, or even if medications change the microbiome in a specific way — all this remains to be understood.