A large metagenomics study determined that gut microbiome is at the centre of Parkinson’s disease pathogenesis.
The largest microbiome study conducted at the highest resolution concluded the gut microbiome is involved in multiple pathways in the pathogenesis of Parkinson’s disease (PD).
The findings, published in Nature Communications, show a wide imbalance in microbiome composition in people with Parkinson’s.
Investigators at the University of Alabama at Birmingham, US employed metagenomics, the study of genetic material recovered directly from the stool microbiome of individuals with PD and neurologically healthy control subjects.
Studying the microbiome of Parkinson’s patients
The research reported Parkinson’s disease metagenome is indicative of a disease-promoting microbiome. “We found evidence for multiple mechanisms that we know are linked to PD, but we didn’t know they were happening in the gut also and are orchestrated by the microbiome,” explained Professor Haydeh Payami, PhD, Marnix E. Heersink School of Medicine Department of Neurology and senior author on the study.
Ultimately, the study found an overabundance of opportunistic pathogens and immunogenic components – suggesting infection and inflammation at play, overproduction of toxic molecules, and overabundance of the bacterial product curli. This induces PD pathology and dysregulation of neurotransmitters, including L-dopa, an amino acid. Results showed there was also a shortage of neuroprotective molecules and anti-inflammatory components, which makes recovery difficult.
Data from the study on gut microbiome
The study enrolled 490 people with PD and 234 healthy controls. Just over half of the subjects were male and were predominately older than 50. All were from the Deep South region of the United States, which helped to eliminate confounding by geographic and cultural influence on composition of gut microbiome.
The researchers studied 257 species of organisms in the microbiome. “Of the 84 PD-associated species, 55 had abnormally high abundance in persons with PD, and 29 were depleted,” Payami reflected. “We found that over 30 percent of the micro-organisms and bacterial genes and pathways tested have altered abundances in Parkinson’s disease, which indicates a widespread imbalance.”
The gut microbiome study “… created a large dataset at the highest resolution currently feasible and made it public with no restriction to promote open science,” Payami shared. “It includes extensive metadata on 490 persons with PD, the largest PD cohort with microbiome data, and a unique cohort of 234 neurologically healthy elderly, which can be used in a wide range of studies.”
Payami expected that, “Undoubtedly more information will be revealed as we increase the sample size and others also conduct metagenomics studies and share the data.”
“We anticipate that in the near future we will have the tools and the analytic power to use metagenomics as a new approach to study PD heterogeneity, search for biomarkers, delve deeper into the origin and progression of PD sub-phenotypes, and investigate the potential in manipulating the microbiome to prevent, treat and halt the progression of PD,” Payami stated.
The research was supported by the US Army Medical Research Material Command, the National Institutes of Health (NIH), the Parkinson’s Foundation and Aligning Science Across Parkinson’s through the Michael J. Fox Foundation for Parkinson’s Research.
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