‘Widespread Imbalance’ Seen in Gut Microbiome of Parkinson’s Patients
Overabundance of damaging microbial species and fewer neuroprotective ones
More than 30% of gut microbial species are found at abnormal numbers in Parkinson’s disease patients, according to a new analysis that assessed the gut microbiome in more detail than most prior studies.
“We have shown that there is a widespread imbalance in the Parkinson’s [gut bacteria], creating an environment that is permissive for neurodegenerative events and is prohibitive of recovery,” Haydeh Payami, PhD, the study’s senior author and a professor at the University of Alabama at Birmingham’s Marnix E. Heersink School of Medicine, said in an university press release.
The study, “Metagenomics of Parkinson’s disease implicates the gut microbiome in multiple disease mechanisms,” was published in Nature Communications.
The human digestive tract is home to billions of bacteria and other microorganisms that are known as the gut microbiome. These microbes play critical roles in health, and they can have far-reaching effects across the body, including in the nervous system.
Analyzing dysbiosis, or imbalance, across species in gut microbiome
Accumulating research suggests the gut microbiome is imbalanced in Parkinson’s patients, a state called dysbiosis. While the idea has yet to be proven, some scientists think that the processes behind Parkinson’s may start with gut dysbiosis, at least in some cases.
While some data to support this hypothesis, many studies have had contradictory or inconsistent results. Most studies on the gut microbiome in Parkinson’s have been fairly small, and most have looked at alterations in bacteria at only the genus level — assessing related groups of bacteria, rather than individual species.
Payami’s team and colleagues in the U.S. and the U.K. performed detailed gut microbiome analyses in stool samples from 490 people with Parkinson’s and 234 people with no neurological disorders, used as controls.
Both groups contained a roughly even split of men and women, and more than 90% of participants were age 50 older. More than half of the controls were spouses of patients in the study and therefore shared the same environment.
All participants lived in the southeastern U.S., helping to eliminate the potential effects of different geographic regions and cultures on the gut microbiome.
To assess these microbes at the species level, the researchers employed a tool called metagenomics. Simply put, this involves analyzing the DNA found in a sample, then using computer algorithms to match the genetic sequences detected with known species of bacteria and other organisms.
“The primary aim of this study was to generate a full, unaltered view of the dysbiosis in PD [Parkinson’s disease] gut microbiome,” the scientists wrote.
“This is exciting research, as metagenomics is a new, albeit fast-evolving field, and the resources, methods and tools, while state-of-the-art, are still in development,” said Payami, who holds an endowed chair in neurology at the university.
Across the different species identified, about a third — 84 out of 257 — showed dysbiosis in Parkinson’s compared with healthy controls. Specifically, 55 of these species were present at unusually high levels in people with Parkinson’s, while the other 29 were at lower levels in patients relative to controls.
“Overall, 36% (30 of 84) of PD-associated species had higher than two-fold change in abundance … reflecting a 100% to 750% increase or decrease in PD vs. [healthy controls],” the researchers wrote.
Finding “that over 30 percent of the micro-organisms and bacterial genes and pathways tested have altered abundances in Parkinson’s disease … indicates a widespread imbalance,” Payami said.
The researchers noted that the size of these differences was often quite large.
For example, the abundance of some bacterial species — including Bifidobacterium dentium, Actinomyces oris, and Streptococcus mutans — was at least six times higher, on average, in patients than in controls. On the other end of the spectrum, levels of the Roseburia intestinalis bacterium were reduced by 7.5 times in patients compared with controls.
When adjusting for other factors that could potentially affect the gut microbiome, such as alcohol consumption or the use of laxatives, the size of the associations tended to diminish.
A Parkinson’s gut microbiome that’s ‘disease permissive’
Nonetheless, most of the bacterial species identified in the initial analysis — 62 out of 84 — still showed statistically significant associations with Parkinson’s after these adjustments.
These species-level analyses “align with existing literature and resolve inconsistencies” among prior studies done at the genus level, the researchers added.
Some closely related species showed differences in Parkinson’s-related associations, which the researchers said could explain why some studies looking at closely related groups fail to show consistent results.
“At the same time, the results generated here confirmed, in humans, several observations that were made experimentally in animal models,” the researchers wrote.
Further analyses showed that the “PD microbiome is disease permissive,” the team wrote.
This was evidenced by an overabundance of disease-causing microbes and molecules that can trigger immune responses and promote the toxic aggregation of alpha-synuclein protein — a hallmark of the neurodegenerative disease.
At the same time, data indicated a “reduction in anti-inflammatory and neuroprotective factors limiting the capacity to recover,” the researchers wrote.
“We show wide-spread dysbiosis in PD microbiome, identify species that drive the dysbiosis, and by functional profiling, nominate microbial genes and pathways in the gut that may contribute to PD mechanisms,” the researchers wrote.
The team stressed that while the results cannot confirm a cause-and-effect relationship between gut dysbiosis and Parkinson’s, this large analysis could be a useful launching point for further research aiming to untangle these microbes’ effects in more detail.
To promote such study, the scientists made their metagenomics database publicly available for other researchers to use.
“This study created a large dataset at the highest resolution currently feasible … which can be used in a wide range of studies,” Payami said, adding that “undoubtedly more information will be revealed as we increase the sample size and others also conduct metagenomics studies and share the data.”
The work was supported by the U.S. Army Medical Research Material Command, the National Institutes of Health, the Parkinson’s Foundation, and Aligning Science Across Parkinson’s, a research effort managed by the Coalition for Aligning Science working with the Michael J. Fox Foundation for Parkinson’s Research.