Axial Biotherapeutics stated that Caltech researchers led by scientific founder Sarkis K. Mazmanian, Ph.D., have established a novel molecular relationship between the gut microbiome and Parkinson's disease. Gut bacteria promoted nervous system inflammation and motor impairment in a validated PD mouse model. The findings show that addressing the gut microbiome may help diagnose and treat Parkinson's disease. The online Cell article, “Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson's Disease,” now available.
Over the past few years, evidence has grown that the gut microbiome is crucial to human health and disease. Bidirectional gut-brain connection is also linked to neurological illnesses such anxiety, depression, and autism spectrum disorders. The Cell study is the first to suggest that gut bacteria may be linked to Parkinson's disease. This discovery may help identify gut microorganisms that affect PD. These bacteria may be employed as biomarkers, PD risk factors, novel therapeutic targets, or microbial-based therapeutics in the future.
“Our findings offer a new perspective on how environmental factors may cause Parkinson's disease and other neurodegenerative diseases. The idea that gut pathology may affect these diseases is a radical departure from conventional neuroscience research, said Dr. Sarkis Mazmanian, the Louis & Nelly Soux Professor of Microbiology in the Division of Biology and Biological Engineering at the California Institute of Technology and Scientific Founder of Axial Biotherapeutics. Parkinson's disease is complex and has several genetic predispositions and environmental dangers, but we believe our findings illuminate a previously unknown and possibly essential aspect of this puzzle.”
Dr. Mazmanian added, “Gut bacteria in Parkinson's patients are different from healthy individuals. When we transplanted Parkinson's microbiomes into mice, motor impairments and neuroinflammation were worse than in mice with healthy gut bacteria. This shows a fundamental link between gut microbes and Parkinson's disease processes.”
A mouse model of Parkinson's disease that overexpresses alpha-synuclein was used for the tests. PD is hypothesized to be caused by this protein. The mice were raised in a germ-free environment. The researchers could then study how gut bacteria affected mouse disease outcomes using germ-free animals. Fecal microbiota transplants from PD patients increased motor deficits, inflammation, and alpha-synuclein aggregation in the model system compared to healthy donor transplants.
Researchers also found microbial metabolites that cause PD in mice. These data imply gut bacteria may cause PD in genetically prone people. Caltech, UC San Diego, Arizona State University, Chalmers University of Technology, Gothenburg, UC Los Angeles, Rush University Medical Center, Chicago, and UW-Madison collaborated on the study.
Dr. Mazmanian said, “Gut bacteria provide immense physiological benefit, and we do not yet have the data to know which species are problematic or beneficial in Parkinson’s disease. It is critical to emphasize that no human antibiotic or microbial therapy can match the effect we found in mice. We will next investigate gut bacteria that may contribute to Parkinson's disease to develop novel biomarkers to identify at-risk patients. These findings could also lead to safer, more effective therapeutic techniques that circumvent brain drug delivery issues.
T. Sampson, J. Debelius, T. Thron, S. Janssen, G. Shastri, Z. Ilhan, Z., S. Mazmanian (2016). Cell, 167(6). Gut microbiota regulate motor deficits and neuroinflammation in a Parkinson's disease model. doi:10.1016/j.cell.2016.11.018
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