The Gut Microbiome is Distinct in Parkinson's Disease

Parkinson's disease is characterized by aggregation of α-synuclein, one of a number of harmful protein aggregates that form and spread in the aging brain. At present, it is thought that in many patients this process of aggregation starts in the intestines rather than in the brain. So it is perhaps not that surprising to find that alterations in the balance of microbial populations in the gut microbiome are characteristic of Parkinson's disease. Researchers have been looking into correlations between the microbiome and various age-related diseases with increasing energy for some years now.

Exactly how the gut microbiome contributes to Parkinson's is yet to be established. It may be as simple as the consequence of increased inflammatory signaling as populations of harmful microbes grow in number. That is an attractive argument, given the disruptive nature of chronic inflammation, but wagering on a biological process turning out to be simple is rarely a winning proposition. Regardless of underlying mechanisms, given that the state of the microbiome can be both measured via 16S rRNA sequencing and radically adjusted via fecal microbiota transplantation, there is the possibility of (a) effective screening for risk of Parkinson's, and perhaps (b) effective prevention via restoration of a healthy balance of microbial populations.

New study puts gut microbiome at the center of Parkinson's disease pathogenesis

Investigators employed metagenomics, the study of genetic material recovered directly from the stool microbiome of persons with Parkinson's disease (PD) and neurologically healthy control subjects. 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.

The researchers studied 257 species of organisms in the microbiome, and of these, analysis indicated 84, more than 30 percent, 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. At one end of the spectrum, Bifidobacterium dentium was elevated by sevenfold, Actinomyces oris by 6.5-fold and Streptococcus mutans by sixfold. At the other end of the spectrum, Roseburia intestinalis was reduced by 7.5-fold and Blautia wexlerae by fivefold.

"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."

Metagenomics of Parkinson's disease implicates the gut microbiome in multiple disease mechanisms

Parkinson's disease (PD) may start in the gut and spread to the brain. To investigate the role of gut microbiome, we conducted a large-scale study, at high taxonomic resolution, using uniform standardized methods from start to end. We enrolled 490 PD and 234 control individuals, conducted deep shotgun sequencing of fecal DNA, followed by metagenome-wide association studies to declare disease association, network analysis to identify polymicrobial clusters, and functional profiling.

Here we show that over 30% of species, genes, and pathways tested have altered abundances in PD, depicting a widespread dysbiosis. PD-associated species form polymicrobial clusters that grow or shrink together, and some compete. PD microbiome is disease permissive, evidenced by overabundance of pathogens and immunogenic components, dysregulated neuroactive signaling, preponderance of molecules that induce alpha-synuclein pathology, and over-production of toxicants; with the reduction in anti-inflammatory and neuroprotective factors limiting the capacity to recover.

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