Gut Microbiome at the Center of Parkinson’s Disease Pathogenesis

Summary: Adding to previous research on the gut-brain axis link to Parkinson’s disease, researchers discovered the gut microbiome is involved with multiple pathways in the pathogenesis of Parkinson’s.

Source: University of Alabama at Birmingham

New research from the University of Alabama at Birmingham says the gut microbiome is involved in multiple pathways in the pathogenesis of Parkinson’s disease.

The findings, published in Nature Communications, show a wide imbalance in microbiome composition in persons with Parkinson’s disease.

The study is the largest microbiome study conducted at the highest resolution.

The investigators employed metagenomics, the study of genetic material recovered directly from the stool microbiome of persons with PD and neurologically healthy control subjects.

“The primary aim of this study was to generate a full, unaltered view of the imbalance in PD gut microbiome,” said Haydeh Payami, Ph.D., professor in the Marnix E. Heersink School of Medicine Department of Neurology and senior author on the study.

The study reports 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,” Payami said.

Investigators found an overabundance of opportunistic pathogens and immunogenic components, which suggest 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. At the same time, there was a shortage of neuroprotective molecules and anti-inflammatory components, which makes recovery difficult.

Payami, who is the John T. and Juanelle D. Strain Endowed Chair in Neurology, and her team enrolled 490 persons with Parkinson’s disease 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 microbiome.

The researchers studied 257 species of organisms in the microbiome, and of these, analysis indicated 84, more than 30%, were associated with Parkinson’s disease.

“Of the 84 PD-associated species, 55 had abnormally high abundance in persons with PD, and 29 were depleted,” Payami said. “We found that over 30% of the micro-organisms and bacterial genes and pathways tested have altered abundances in Parkinson’s disease, which indicates a widespread imbalance.”

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Gut Microbiome at the Center of Parkinson’s Disease Pathogenesis

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