The gut microbiome is not only an influencing factor in Parkinson's disease, but also the center of its onset

A new study from the University of Alabama at Birmingham shows that the gut microbiome is involved in multiple pathways
in the onset of Parkinson's disease.
The findings, published in Nature Communications, show a wide imbalance
in the composition of the microbiome in people with Parkinson's disease.
This study is the largest microbiome study
conducted at the highest resolution.

The researchers employed metagenomics to analyze genetic material
recovered directly from the fecal microbiome of Parkinson's disease patients and neurohealth controls.

Dr Haydeh Payami, senior author of the study, said: "The main objective of this study is to generate a complete, unchanging view
of the imbalance of the PD gut microbiota.
"

The study reports that the metagenomic genome for Parkinson's disease predicts a disease-promoting microbiome
.

"We found evidence of multiple mechanisms involved in Parkinson's disease, but we didn't know they also occur in the gut and were carefully orchestrated by the microbiome
," Payami said.

The researchers found an excess of opportunistic pathogens and immunogenic components, suggesting that infection and inflammation were at work, that toxic molecules were produced in excess, and that the bacterial product curli was too much
fimbriae.
This leads to PD pathology and dysregulation of neurotransmitters, including levodopa
.
At the same time, neuroprotective molecules and anti-inflammatory components are lacking, which makes recovery difficult
.

Payami, the John T.
and Juanelle D.
Strain Endowment Chair in Neurology, and she and her team recruited 490 Parkinson's patients and 234 healthy controls
.
More than half of the participants studied were men, and most were over
the age of 50.
All were from the southern region of the United States, which helped eliminate the influence
of geography and culture on the composition of the microbiome.

The researchers studied 257 organisms in the microbiome, and analysis showed that 84 of them, more than 30 percent, were associated
with Parkinson's disease.

"Of the 84 species associated with PD, 55 have unusually high abundances in PD patients and 29 are depleted
," Payami said.
"We found that more than 30 percent of microbial and bacterial genes and pathways altered abundance in Parkinson's disease, suggesting a widespread imbalance
.
"

The researchers analyzed a 7-fold increase in Bifidobacterium dentito, a 6.
5-fold increase in Actinomycetes oral, and a 6-fold
increase in Streptococcus mutans.
Conversely, Roseburia ntestinalis decreased by a factor of 7.
5 and Blautia wexlerae by a factor of 5
.
Overall, 36 percent of PD-associated species had more than twofold changes in abundance, and PD increased or decreased by 100 to 750 percent
compared to healthy controls.

"This study creates a large dataset at the highest resolution currently available and makes it public without any restrictions, to promote open science
," Payami said.
It includes extensive metadata for 490 PD patients, the largest PD cohort with microbiome data, and a unique cohort of 234 neurologically healthy older adults that can be used for a wide range of studies
.
We have shown that Parkinson's metagenomic has a wide imbalance, creating an environment that allows neurodegenerative events to occur and prohibits recovery
.
”

Parkinson's disease is a debilitating disease that affected 4 million people in 2005 and is expected to double to 8.
7 million by
2030.
Although historically defined as a movement disorder, PD is a multisystem disease
.
It is hypothesized that Parkinson's disease is caused by various combinations of genetic predisposition and environmental triggers, although combinations of etiologies have not been identified
.
The link between Parkinson's disease and the gastrointestinal system has long been established
.

"This is an exciting study because metagenomics is a rapidly evolving new field where resources, methods, and tools, while state-of-the-art, are still under development
," Payami said.
"There is no doubt that as we increase the sample size, others will also do metagenomics research and share the data, and more information will be revealed
.
" We anticipate that in the near future, we will have the tools and analytical capabilities to use metagenomics as a new way to study PD heterogeneity, search for biomarkers, study more deeply the origin and progression of PD subphenotypes, and investigate the potential
to manipulate the microbiome to prevent, treat, and stop PD progression.
”

The research was supported by the U.
S.
Army Medical Research Materials Command, the National Institutes of Health, the Parkinson's Foundation, and the Michael J.
Fox Parkinson's Research Foundation for scientific research on Parkinson's disease
.

Journal Reference:

1. Zachary D.
   Wallen, Ayse Demirkan, Guy Twa, Gwendolyn Cohen, Marissa N.
   Dean, David G.
   Standaert, Timothy R.
   Sampson, Haydeh Payami.
   Metagenomics of Parkinson’ s disease implicates the gut microbiome in multiple disease mechanisms.
   Nature Communications, 2022; 13 (1) DOI: 10.
   1038/s41467-022-34667-x