Summary: In addition to previous research on the link between the gut-brain axis and Parkinson’s disease, researchers have found that the gut microbiome is involved in multiple pathways in the pathogenesis of Parkinson’s disease.
Source: University of Alabama at Birmingham
New research from the University of Alabama at Birmingham indicates that the gut microbiome is involved in multiple pathways in the pathogenesis of Parkinson’s disease.
The findings, published in Nature Communicationshow a large imbalance in the composition of the microbiome in people with Parkinson’s disease.
The study is the largest microbiome study conducted at the highest resolution.
Investigators used metagenomics, the study of genetic material retrieved directly from the stool microbiome of people with PD and neurologically healthy control subjects.
“The primary goal of this study was to generate a comprehensive and unaltered view of the gut microbiome imbalance of PD,” said Haydeh Payami, Ph.D., professor in the Department of Neurology at the Marnix E. Heersink School of Medicine. and lead author on the study.
The study reports that the Parkinson’s disease metagenome is indicative of a disease-promoting microbiome.
“We found evidence for several mechanisms that we know are related to PD, but we didn’t know that they also occur in the gut and are orchestrated by the microbiome,” Payami said.
Investigators found an overabundance of opportunistic pathogens and immunogenic components, suggesting infection and inflammation at play, an overproduction of toxic molecules, and a curli overabundance of bacterial products. This induces PD pathology and dysregulation of neurotransmitters, including L-dopa. At the same time, there was a shortage of neuroprotective molecules and anti-inflammatory components, which makes recovery difficult.
Payami, John T. and Juanelle D. Strain Endowed Chair in Neurology, and his team recruited 490 people with Parkinson’s disease and 234 healthy controls. Just over half of the subjects were male and were mostly over 50 years old. All were from the Deep South region of the United States, which helped eliminate confusion by geographic and cultural influence on microbiome composition.
The researchers studied 257 species of organisms in the microbiome, and of these, the analysis indicated that 84, more than 30%, were associated with Parkinson’s disease.
“Of the 84 species associated with PD, 55 had abnormally high abundance in people with PD, and 29 were depleted,” Payami said. “We found that more than 30% of tested microorganisms and bacterial genes and pathways have altered abundances in Parkinson’s disease, indicating a generalized imbalance.”
At one end of the spectrum, Bifidobacterium dentium increased seven-fold, Actinomyces oris 6.5-fold, and Streptococcus mutans six-fold. At the other end of the spectrum, Roseburia intestinalis was reduced 7.5 times and Blautia wexlerae five times. Overall, 36% of species associated with PD had a more than doubled change in abundance, reflecting a 100% to 750% increase or decrease in PD compared to the healthy control group.
“This study created a large dataset at the highest resolution currently possible and made it publicly available without restriction to promote open science,” Payami said.
“It includes extensive metadata on 490 people with PD, the largest PD cohort with microbiome data, and a unique cohort of 234 neurologically healthy older adults, which can be used in a wide range of studies. We have shown that there is a generalized imbalance in the Parkinson’s disease metagenome, creating an environment conducive to neurodegenerative events and preventing recovery.
Parkinson’s disease is a progressively debilitating disorder that affected 4 million people in 2005 and is expected to double to 8.7 million people by 2030. Although historically defined as a movement disorder, PD is a disease multisystemic. PD is thought to be caused by various combinations of genetic susceptibility and environmental triggers, although no causal combination has yet been identified. The link between PD and the gastrointestinal system has long been established.
“This is exciting research, as metagenomics is a new, albeit rapidly evolving field, and the resources, methods and tools, while state-of-the-art, are still under development,” Payami said.
“Undoubtedly, more information will be revealed as we increase the sample size and as others also conduct metagenomics studies and share the data. We anticipate that in the near future we will have the tools and the analytical power to use metagenomics as a novel approach to study PD heterogeneity, search for biomarkers, dig deeper into the origin and progression of PD subphenotypes, and investigate the potential to manipulate the microbiome to prevent, treat and halt the progression of PD.
About this Parkinson’s disease research news
Author: Bob Shepard
Source: University of Alabama at Birmingham
Contact: Bob Shepard – University of Alabama at Birmingham
Image: Image is in public domain
Original research: Free access.
“Parkinson’s disease metagenomics implicates the gut microbiome in multiple disease mechanisms” by Zachary D. Wallen et al. Nature Communication
Metagenomics of Parkinson’s disease implicates the gut microbiome in multiple disease mechanisms
Parkinson’s disease (PD) can start in the gut and spread to the brain. To investigate the role of the gut microbiome, we conducted a large scale, high taxonomic resolution study using uniform standardized methods from start to finish.
We recruited 490 PD individuals and 234 controls, performed deep fecal DNA sequencing, followed by metagenome-wide association studies requiring significance by two methods (ANCOM-BC and MaAsLin2) to report the disease association, network analysis to identify polymicrobial clusters and functional profiling.
Here we show that more than 30% of species, genes and pathways tested have altered abundances in PD, illustrating generalized dysbiosis. Species associated with PD form polymicrobial clusters that grow or shrink together, and some compete.
The PD microbiome is permissive to disease, as evidenced by overabundance of pathogens and immunogenic components, dysregulated neuroactive signaling, preponderance of molecules that induce alpha-synuclein pathology, and overproduction of toxicants; with the reduction of anti-inflammatory and neuroprotective factors limiting the ability to recover.
We validate, in human PD, the results that have been observed in experimental models; reconcile and resolve the human PD microbiome literature; and provide a broad base with a multitude of concrete testable hypotheses to discern the role of the gut microbiome in PD.
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